Introduction

After the second World war Europe was totally devised by the “iron curtain”. Eastern and Western Europe had no longer contacts and specialists in urology could no longer assist medical congresses at the other side of the curtain. Collaboration between East and West was completely impossible.

Methods

Nevertheless, around 1970, some individual professors in urology were allowed to cross the curtain and the idea of an European Association of Urology was in the air. At the meeting of the Association Française d’Urologie in 1972, in Paris, the European Society of Urology was founded as a very private and closed society with a selection of only 150 European urologists from Eastern and Western Europe.

Results

After a second preliminary meeting in Zürich and at the SIU congress in Amsterdam in 1973 the name was changed in European association of Urology and the 19 founding Fathers decided to hold the 1st congress in 1974 in Pavia (Italy). Prof. Ravasini was the first chairman and the congress was planned every 2 years._x000D_ Since 1975 the official Journal of the EAU was “European Urology” and Claude Schulman was editor till 2005._x000D_ In 1990, Frans Debruyne, chairman of the 9th EAU Congress in Amsterdam, decided that the congress should be open for all European urologists. This congress was a milestone in the history of the EAU and was attended by 1500 participants._x000D_ Since 1998 the congress was organised every year and the number of participants grew constantly with a peak of 13489 attendants in Milan (Italy) in 2008._x000D_ The EAU is now organised in 15 scientific sections and the office moved from Nijmegen to Arnhem in 1999._x000D_ Since 2004 there is an intensive collaboration between the EAU and the EBU (European Board of Urology) and both have their headquarters in Arnhem. The EAU has a scientific and educational role, the EBU has a regulatory role._x000D_

Conclusions

What was only a dream and at that time perhaps an illusion to found an European group of a small selected group of urologists in 1970, developed into a big and powerful European association of Urology, open for all urologists all over the world.

Funding

none

Introduction

The experimental studies of Zambercari (1670) showed that unilateral nephrectomy has no impact on the survival of animals. Borelli (1680) presented a revolutionary theory of the kidney acting as a sieve producing a filtrate of blood. However, initial physiology progress in the 18th century was weakened by two main sources of medical science, which opposed experimental studies: Morbid anatomy and Naturphilosophie. Morbid anatomy explained the disease based on clinico-anatomical observation . Naturphilosophie , a major philosophical doctrine in science, proclaimed the laws of nature form the lecturing desk . In the 19th century, function slowly became a measuring unit of physiological studies. Comhaire (1803) observed no urine production after bilateral nephrectomy. Coindet (1820)demonstrated no urine production after bilateral ligation of renal vessels. However, the first true experimental study of kidney function became possible by the progress in chemistry and young Geneva scientists: physician J.L. Prevost and pharmacist's apprentice J.B. Dumas.

Methods

Review of original papers 1670-1825

Results

In 1820, the nature of urea, first marker of the kidney function, was fiercely debated: does it circulates in the blood or produced by the kidney? Prevost and Dumas decided to &[Prime]put an end to the vagueness of accepted ideas and replace it by positive facts&[Prime]. They chose the old model of bilateral nephrectomy but, instead of relying entirely on anatomical and autopsy findings, reinforced it by new quantitative measurement of urea in blood and urine. The experiments took place in a fortification of the Geneva guards between 2-3 AM, since vivisection was prohibited in the city. Initially the researchers confirmed that urea crystals from the blood and urine of the animals were the same . The urea was lower in the blood of control group but doubled in binephrectomised animals. It was concluded that &[Prime]the kidney is only an eliminating surface, it does not produce urea&[Prime]. The study , presented before the Geneva Society of Physics and Natural History on 11/15/1821 , &[Prime]puts an end to all alternative theories&[Prime]. _x000D_

Conclusions

Prevost and Dumas pioneered quantitative experimental renal physiology at a time of triumphant anatomo-clinic and philosophical approach to medical science. Their rigorous landmark study , mostly forgotten, became a model of the future coordinated physiological research using innovative new methods of chemical control. _x000D_ Eventually,serum BUN/Cr became the main clinical test of kidney function.But the foundation for experimental renal physiology was set 196 years ago

Funding

None

Introduction

Wolfgang Amadeus Mozart (1756 to 1791) was a child prodigy and prodigious composer whose works remain popular today. His premature death at the age of 35 provoked many theories which are still debated. I aim to outline the theories surrounding Mozart&[prime]s early death.

Methods

Literature review

Results

Mozart had bouts of ill health starting in childhood and recurring throughout his life. This is unsurprising as at the time childhood mortality was high (only Mozart and his sister survived to adulthood of 7 siblings). Mozart&[prime]s recorded medical complaints include scarlet fever and an ulcerous molar (age 7). This complaint became chronic and troubled Mozart throughout his life. Aged 9 he almost died of abdominal typhus and aged 10 he contracted smallpox. He also suffered from articular rheumatism. In his early teens he suffered frostbite on both hands and his face. In 1784 the first of several attacks of renal colic was recorded. In the later years of his life he complained of severe headaches, nosebleeds, difficulty in concentrating and depression._x000D_ _x000D_ Mozart became unwell in Prague on the 6th September 1791. His heath further declined on the 20th November with symptoms of pain and swelling in his limbs, headache, pyrexia and later vomiting and diarrhoea. The edema worsened and Mozart became bedridden and increasingly agitated. Delirium then coma followed before Mozart died on December 5th 1791._x000D_ _x000D_ His death certificate records the cause of death as &[Prime]severe miliary fever&[Prime]. A week after his death a newspaper published claims that he had been poisoned._x000D_ Since then at least 118 causes of death have been suggested including rheumatic fever, streptococcal infection, vasculitis causing renal failure, acute glomerulonephritis, trichinosis, thyrotoxic crisis, influenza , infection following a bloodletting procedure, syphilis and mercury poisoning (either an accidental side effect of treatment for syphilis or murder). Various murder and conspiracy theories have been suggested. The accused include the royal band master Antonio Salieri, Mozart&[prime]s physician and friend Gottfried van Swieten or even Mozart&[prime]s Freemason lodge. There is, however, no historical evidence to support these claims._x000D_

Conclusions

Mozart&[prime]s grave has been lost so it seems unlikely that we will ever have a definitive answer to the mystery of his death. The most probable theory seems to be an acute exacerbation of chronic kidney disease causing uraemia, likely secondary to febrile illness.

Funding

None

Introduction

In 1917, Alma Hiller became the first woman to publish in the Journal of Urology (JU). Her contribution was soon followed by articles from Carol Beeler and Dr. Isabel Mary Wason. Dr. Wason (1890-1972) became the first female lead author in JU. This study explores their careers and contributions, especially those of Dr. Wason.

Methods

We reviewed JU articles from 1917 to 1925 and identified Hiller, Beeler, and Dr. Wason as the first three women authors. We contacted librarians and archivists to obtain records of their education, academic appointments, and publications.

Results

In 1917, JU&[prime]s first issue featured &[Prime]The Relation of the Non-Protein Nitrogen to the Urea Nitrogen of the Blood&[Prime] by Hiller and Dr. Herman Mosenthal. Subsequently, in 1918, Beeler and Dr. HF Helmholz published &[Prime]Experimental Pyelitis in the Rabbit.&[Prime] Hiller and Beeler worked with their male co-authors as a biochemist and technician, respectively. It wasn't until 1920 that Dr. Wason published &[Prime]Report of a Case of Congenital Stenosis of Both Ureteral Orifices&[Prime] in JU, her first paper as a Pathologist._x000D_ _x000D_ Dr. Wason earned her degree in 1911 from The Western College for Women, where she stayed to complete a fellowship in Chemistry. She applied to Johns Hopkins Medical School (JHMS) in 1912. After graduating in 1917, Dr. Wason was recruited by Dr. Milton, the Yale Pathology Department Chair, to become the first woman instructor within the department (Figure 1). During her early career, she published three papers and a textbook on the pathologies of infection and nutritional deficiency, in addition to urogenital disease._x000D_ _x000D_ With her considerable body of experience, Dr. Wason moved to St. Luke&[prime]s Hospital (SLH) in Massachusetts in 1925 where she served as laboratory director. Dr. Winternitz described Dr. Wason as a &[Prime]splendid pathologist, a good bacteriologist, [with] considerable experience in clinical pathology, surgical pathology and chemical [l]ab analyses&[Prime] in letters to SLH. She stayed at SLH through 1943._x000D_ _x000D_ Figure 1: Dr. Wason with colleagues at YUSM in 1924.

Conclusions

During an era in which female physicians were few and far between, Dr. Wason distinguished herself as an academic Pathologist. Her relationship with the field of Urology, along with that Heller and Beeler, is of historical significance.

Funding

none

Introduction

Upon reading this abstract title did you imagine Dr Gannon as a male urologist? Dr Mary Gannon was the 2nd woman, following Dr Elisabeth Pickett, to become a board certified urologist. She was the 1st female urologist elected to the AUA (1975).

Methods

We interviewed Dr Gannon and researched media, text and articles pertaining to her life and women in urology.

Results

Mary Louise Gannon was born in 1941 in Des Moines, Iowa. She grew up on a farm and aspired to become a veterinarian but was told she could not apply to veterinary school because of her gender. This led her to say "if you aren't going to allow me to take care of animals then I'll take care of humans."_x000D_ _x000D_ She was one of 5 women admitted to her medical school class at the University of Iowa, College of Medicine (1962-1966). She became interested in urology thanks to her mentor Dr Reuben Flocks and because she enjoyed endoscopy. After completing medical school, she applied to over 30 urology residency programs as "M.L. Gannon" and was accepted to multiple programs until they learned that the "M" stood for "Mary." Ultimately, 3 urology residency programs accepted her and she chose to train at the University of Wisconsin under Dr Weir and Dr Uehling. While in residency she stated she had great support from her attendings, was well accepted by her patients, but that the greatest resistance came from her fellow residents._x000D_ _x000D_ After completing her residency she had difficulty finding a job and tells of one "interview" where after spending a day with a practicing urologist, she was told that they were not looking to hire her but had "wanted to see what a female urologist looked like." The lack of equal opportunities as a urologist led her to open her own practice in Spencer, Iowa and she practiced from 1972-1984. She stopped practicing urology in 1984 because she said she was burned out. _x000D_ _x000D_ Her passion for counseling and working with patients led her to pursue training in psychotherapy and she completed a fellowship and was board certified in addiction medicine. Her mental health background gave her significant insight into her experiences. She feels that her isolation with no significant support system and a lack of lifestyle balance were what made her journey through urology so difficult and led her to eventually leave her field._x000D_

Conclusions

Dr Mary Louise Gannon is a pioneer in urology. Her story illustrates many of the hurdles women have worked to overcome in urology and highlights many current issues in our field. When asked what advice she had for women in the field today, Dr Gannon replied "First find your passion, but also remember you need to find a balance in your life. Seek out good colleagues as having a strong support group is important."

Funding

None

Introduction

Prior to the development of the mignon small light bulb, endoscopes struggled to gain traction in the medical field. The first endoscopes were expensive, cumbersome, and provided poor visualization. The mignon light bulb was a small, inexpensive interchangeable light bulb that screwed into the end of the endoscope allowing significant improvement in visualization.

Methods

A review of textbook chapters, peer-reviewed articles on pubmed, original product catalogues, surgical meeting catalogues, review of Electro Surgical Instruments Co (ESI) office records and company archives and original period instruments were performed on topics related to the development and impact of the mignon lamp.

Results

In 1879 when Edison introduced the light bulb, cystoscopy commonly used external light sources or open platinum incandescent filaments requiring extensive cooling mechanisms. The first urologic use of a modified Edison lamp came in 1883 when David Newman attached a miniature bulb to the end of a cystoscope. Three years later, German urologist Maximillian Nitze and Austrian instrument manufacturer Josef Leiter, introduced a cystoscope incorporating the new technology. Early Edison bulbs caused thermal injuries and were cost prohibitive for all but the most prominent urologists. Dr. Henry Koch, a urologist, and Charles Preston, an electrician, from Rochester, New York, modified the Edison bulb to a smaller size and amperage suitable for medical devices and the mignon lamp was born. ESI Co., founded in 1896 by Koch, Herman Behm, William Maier and Frederick Maier, marketed the mignon bulb as a &[Prime]cold&[Prime] lamp allowing contact with body tissue without the potential for burns and ulcerations. Patented in 1899, the Koch urethroscope was the first instrument to utilize the exchangeable lamps from ESI. The Device had no magnification, only a sheath French 20-33, an obturator and a light carrier with the ESI lamp fixture at the end. Through their collaboration with other notable urologists, including former AUA president Ferdinand C. Valentine, ESI created surgical instruments that allowed urologic diagnosis and treatment to reach new heights.

Conclusions

The mignon lamp, developed by a urologist in conjunction with ESI revolutionized endoscopy not only for urology but for many surgical disciplines. For the first time, endoscopic visualization of the bladder became accessible to the average urologist. Endoscopic illumination using mignon light bulbs was not improved upon until the advent of the quartz rod lens system by Hopkins and Stortz in the second half of the twentieth century.

Funding

none

Introduction

Until the 20th century, visualization beyond tortuous anatomic and mechanical contours posed a perennial hurdle for physicians and military engineers alike. The end of World War II coincided with profound discoveries in imaging through flexible glass fibers. However, discoveries in fiber optics were not widely distributed and gained little traction for practical use. Both Abraham van Heel and Harold Hopkins separately overcame this by publishing their work in Nature, enigmatically, in the same issue. We sought to discover the timeline of events preceding the publications and explain the coincidental timing.

Methods

PubMed, Google Scholar, HathiTrust and ProQuest were searched for sources describing van Heel and Hopkins&[prime] work on fiber optic imaging devices. Also, since both men are deceased we interviewed Jeff Hecht (City of Light: History of Fiber Optics, 1999) and reviewed his research documents, including articles translated from Dutch and correspondence with Hopkins and William Brouwer, van Heel&[prime]s assistant.

Results

Van Heel, professor of optics at the Technical University of Delft in the Netherlands, focused on coating individual glass fibers to maximize the light delivery and potential length of the fibers. Hopkins, a professor of optics at the Imperial College in London, used bundles of many tiny fibers to increase image resolution. Both innovations proved crucial to fiber optics&[prime] success. When Frits Zernike, another Dutch optics expert, learned of Hopkins&[prime] work while receiving his Nobel prize in physics, he shared this information with van Heel and sparked a race to publish._x000D_ Van Heel was the first of the two to publish his findings. The article appeared in De Ingenieur in June 1953, but had geographically limited readership. To address this, van Heel also sent a letter to the editor of Nature. This was received on May 21, 1953, but delayed in publishing until January 2, 1954. 82&[permil] of letters in the 5 issues centered around January 2, 1954 were published within 2 months of receipt. Van Heel&[prime]s letter appears above a longer letter documenting Hopkins&[prime] own work. Although Hopkins denied prior knowledge of van Heel&[prime]s work, Brouwer references Hopkins as the editor of van Heel&[prime]s letter and suggests his role in the delay in publication.

Conclusions

Harold Hopkins&[prime] pioneering work to improve the image quality of the first flexible fiberscopes is well documented. However, van Heel&[prime]s simultaneous and independent contribution of fiber coatings to increase light delivery should also be credited. When considered together, both Hopkins and van Heel&[prime]s discoveries launched modern fiber optics and changed the field of urology forever.

Funding

None

Introduction

Male urinary incontinence has been described from antiquity and various techniques have evolved to treat this disorder.

Methods

A literature review of PubMed articles in English pertaining to male incontinence was performed to compile a historical perspective of the treatment of male incontinence.

Results

Male urinary incontinence was first mentioned in Egyptian manuscripts in 1500 B.C., where papyrus leaves were used &[Prime]to remove constant running of the urine.&[Prime] In 1564, French surgeon Ambroise Pare described one of the first portable urinals for incontinent males. German surgeon Wilhem Hildanus created the first condom catheter with pig bladder in the 1600s and was also credited with creating the first penile clamp; however, it was not popularized until 1980 as the &[Prime]Cunningham clamp.&[Prime] German anatomist and surgeon Lorenz Heister introduced a perineal bulbar urethral compression belt in 1747 which provided the blueprint for air-inflated bulbar urethral compression devices such as the one designed by British physician S.A. Vincent in 1960. Meanwhile, Austrian surgeon Robert Gersuny took his experience with paraffin in plastic surgery and adapted it to urologic care to perform the first periurethral paraffin injection as bulking therapy. Americans entered the field in 1929 when urologist Frederic Foley introduced the modern catheter, which was adopted for management of retention and incontinence. Foley is credited with creation of the first artificial urinary sphincter; however, his version was worn around a surgically isolated segment of the corporal spongiosum. From 1970-73, American urologist Joseph Kaufman described multiple crural crossover procedures which provided surgically created bulbar compression for post-prostatectomy incontinence, but not before designing the first male sling with partner John L. Berry in 1958. The gold standard therapy for male incontinence did not appear until 1973 when American urologist F. Brantley Scott described the first multi-component artificial inflatable sphincter. Improvements upon minimally invasive intraurethral bulking therapy occurred rapidly with Teflon (1973), collagen (1989), autologous adipose tissue (1989) and cross-linked silicone gels (1991). Finally, stem cell therapy has emerged since 2007 to promote regeneration of functional components for adequate urethral coaptation.

Conclusions

Treatment for male urinary incontinence has evolved from noninvasive devices to various surgical procedures, both endoscopic and reconstructive. Artificial sphincters remain the gold-standard therapy for male urinary incontinence.

Funding

None

Introduction

While centuries of physicians and anatomists dating back to Hippocrates and Galen have sought to characterize the functions of the bladder, another group simultaneously found additional uses: cooks.

Methods

Primary and secondary sources describing the multiple uses of the bladder in food preparation were examined.

Results

An early description of the bladder in cooking comes from Greece in Aristophanes' The Clouds. Written in 423 B.C.E., it contains a passage in which the food placed inside a sheep's bladder for roasting spilled out when the bladder ruptured. The Romans found another use, as described in a recipe for suckling pig from the first century A.C.E. The bladder was filled with a dressing and a bird's quill was placed in the bladder neck. The bladder and quill tip were then used like a pastry bag to apply the dressing under the pig's skin for seasoning prior to baking. The bladder played a role in medieval cooking. A fifteenth-century German cookbook includes a recipe for creating a giant egg: several yolks were placed inside a small bladder, which was then placed inside a large bladder filled with egg whites, then cooked. Popular at Lent, saffron and figs substituted for yolks, while ground almonds and pike roe substituted for the whites. The bladder fulfilled multiple functions in 17th and 18th century cooking. Animal bladders, usually cow or sheep in origin, became commonplace in food storage. Fresh or rehydrated dried bladders were used to cover crockery. As the bladders dried, they created an airtight seal, preserving the contents. During this time, bladders became popular as a way to preserve flavor and moisture during cooking, similar to the modern method of sous vide. Meats, poultry, and seasonings were placed inside the bladder (ox bladders were described in the use of cooking whole chickens in 1730), which was then tied and boiled until the contents were fully cooked. The bladder was then opened and discarded. The technique is referred to as en vessie and is still used today in traditional French cooking. The bladder can also be eaten. For centuries, cow bladder has served as casing in the traditional Italian salumi mortadella di Bologna and culatello, and bladders can be used in preparing regional fare such as Scottish haggis, Slovenian ded and vratnik, or French gogue.

Conclusions

Although well known to the masses for storing and emptying waste, a full understanding of the bladder continues to be debated among urologists. Still, the bladder's history of culinary utility in creating and storing foods is irrefutable, proving it to be a versatile organ.

Funding

none

Introduction

The public has long considered cranberry juice to contain properties that prevent urinary tract infections (UTI), a common enough conception that it has been explored repeatedly by scientific bodies. This work highlights the history of the medical opinion regarding the role of cranberries in UTI prevention.

Methods

A literature search including Pubmed and domestic periodicals was performed.

Results

Cranberries were first thought to have medicinal qualities by Native Americans, and their plant leaves used for urinary and gastrointestinal disorders. As early as the 1920s, the scientific community reported that cranberry consumption contributed to the acidification of urine, and over the next decade, this was found to be a result of excreted hippuric acid. Until the 1970s, acidification of the urine was considered to be the utility of cranberries in the prevention of UTIs. Studies aiming to confirm this theory showed no or only a transient effect and new theories were sought. After the discovery of the importance of bacterial adherence in the pathogenesis of UTIs, several studies in the mid- and late-1980s suggested that cranberries prevent the adhesion of bacterial organisms, specifically E. Coli, to the uroepithelial cell walls. Over the next decade, fructose and proanthocyanidins were identified as the &[Prime]active&[Prime] components that exhibit this anti-adhesion property. In the last twenty years, multiple randomized-control and quasi-randomized control studies investigated the effectiveness of cranberry juice, syrups, powders, capsules and tablets in preventing UTIs. An article published in 2000 and sponsored by Ocean Spray Cranberries, Inc. presented a multitude of studies that suggest that regular consumption of cranberry juice cocktail reduces the risk of UTIs and inhibits bacterial adherence to mucosal surfaces. Cochrane reviews in 2000, 1998, 2004, and 2008 evaluated these studies and furthered the notion that there may be a decrease in symptomatic UTIs in women with recurrent infections over a 12-month period. However, the most recent update in 2012, which included 24 studies (14 more than 2008) and 4,473 participants suggested no statistically significant benefit in any high-risk group. Most recently, a study in JAMA found no benefit among women living in nursing homes.

Conclusions

While a mechanism by which cranberry consumption may theoretically prevent UTIs has been proposed, and some research has suggested a benefit, a lack of strong evidence has left the most current medical opinion unable to justify proactive physician support of the practice.

Funding

none

Introduction

The Mount Sinai Hospital in New York City, heralded some of the very first innovations in urology at the turn of the 20th century. Sarah Bernhardt was at the peak of her international reputation and was touring the U.S. when she became ill with obstructive pyohydronephrosis.

Methods

A review of the literature of Ms. Bernhardts life and illnesses was cross-referenced to surviving documents of the event from the Emanuel Libman Archives at the National Library of Medicine. Leo Buerger, the urologist who operated upon Ms. Bernhardt is even more apocryphal and difficult to pursue, though he was the Buerger of the Brown-Buerger cystoscope fame. Dr. Emanuel Libman proved to be the key player who actually kept hospital records recording the events of her Tuesday, April 17th 1917 surgery.

Results

Sarah Bernhardt is considered by many to be the first actress superstar of the modern era, bridging into the silent movie era. She may well have suffered from tuberculosis throughout her long life, but an injury to her leg resulted in an amputation, late in life and during her final U.S. tour she was often unwell. She became ill and was brought to Mount Sinai Hospital in New York City in critical condition. She had a left pyohydronephrosis with an obstructing calculus. Cystoscopy and retrograde evacuation of pus was performed first on Saturday July 14th. Buerger records that a large amount of pus washed out from left kidney. She did not do well, though and by the evening of Tuesday, July 17th it was deemed her situation was critical enough to warrant emergent open surgery. He records, Incision was made into the kidney and six ounces of foul smelling pus obtained. Large irregular calculus in the pelvis, which was removed. We also have the records of her hospital vital signs which clearly show her post-operative improvement. With no available antibiotics it is almost miraculous that she survived. She adopted Buergers only daughter, Yvonne as her godmother and became close to Germaine Schnitzer, Buergers wife.

Conclusions

Of the five attending physicians who cared for Ms. Bernhardt, she kept in contact with both Buerger and Libman in her final years. She was a dynamo of activity working on another silent movie in her final year, dying on March 26, 1923 in Paris. Dr. Buergers life apparently fell to pieces following this surgery, becoming a footnote only in the history of urology.

Funding

None

Introduction

Outlining history from a patient's view is a major theme in the social and cultural history of medicine. Since Porters work in the 1980th "patients view meets the clinical gaze" (Condrau 2012). Within the research on the history of urology there could be traced besides Margarethe Kleb (1820-1878), a washer women, (nephrectomy), and Theodor Baum of Cologne (1830-1886) (first indicated cystectomy) only some famous patients who had written ego-documents as Samuel Pepys (1633-1703), Chief Secretary to the Admiralty of Great Britain and his diaries or the report on Jan de Doot by Nicholaes Tulp (1593 - 1674). Other famous urologic patients were Napoleon III. (1808-1873) or Michel de Montainge (1533 -1592) whose legacy should not be lost (Moran, 2013)._x000D_ Mary Helen Schirm (1840-1871) nee Williams from Savannah (Georgia) was suffering from kidney stones for years. She had married an immigrant from Germany, Wilhelm Philip Schirm (1836-1896) from Scheuern near Nassau/Lahn, who came to the US in 1857 and served during the Civil War in the 3rd Georgia battalion of the Confedered Army. Two pregnancies of Mary were interrupted due to renal colics._x000D_ Therefore she sought urgent help. At that time giving birth to a son and heier was a major "task" of a married women. With the popularized information about first successfull nephrectomy from the department of Gustav Simon (1824-1876) from Heidelberg, about 80 km away form her husbands former home, she traveld to Germany. The operation took place on August 8th 1871 but the patient died about one month later and was buried in Obernhof/Lahn where the German relatives were living._x000D_

Methods

An analysis of the local and scientific reports and primary sources on the patient, the operation and the person of Gustav Simon will be combined with a social analysis a the medical system in the last quarter of the 19th century in Germany and the US.

Results

The first indicated operations proved that it is possible to remove one kidney in a human being and that a patient can survive with only one kidney. However, nephrectomy slowly gained acceptance due to a lethality rate about 40% at the early years. At the turn to the 20th century operation became the major corner stone to define the new specialty of urology besides endoscopy.

Conclusions

The study is intended to suggest the dimensions international communication had on the differentiating specialty of urology. In its general perspective, the study tries to understand the dimension of a history of patients view in the history of urology especially in Germany, Europe and the US.

Funding

non

Introduction

The prostate gland was ill understood until the Renaissance when anatomists discovered the organ naming it "glandulous body." In 1600 the French physician du Laurens introduced the name "prostatae" (Josef et al. 2009). Modern insight into the anatomy of the gland was supplemented by McNeal&[prime]s description of the zonal anatomy of the prostate (1981), and by rapid surgical advances in surgical technology. This is a review of recent developments in understanding of the prostate through robotic and laparoscopic urological surgery.

Methods

A systematic literature search of PubMed, Medline, EMBASE, textbook chapters and historical archives was performed.

Results

The introduction of laparoscopic radical prostatectomy (LRP) allowed assessment of the prostate and its anatomical relations with heighted magnification and new visual angles. Robotic surgical systems further enhanced visualisation, with superior magnification and additional three-dimensional views. New anatomical understanding led to modifications of surgical technique aiming to preserve continence and potency. In 2002, it was noted that important relationships existed between pelvic plexus ganglions and seminal vesicles. Further fine neural plexuses along the posterior and antero-lateral surface of the prostate were described based on cadaveric studies and laparoscopic and robotic views. Later on, the technique of nerve preservation in which a plane (deep to the Santorinis plexus) between the prostatic capsule and inner prostatic fascial layer is developed at its cranial extent was described (i.e. the Veil of Aphrodite). In 2003-2004, Lunacek et al. noted that the cavernosal nerves running along the prostate become displaced further anteriorly and spread, thus forming a concave shape (like a &[prime]curtain&[prime]) of the neurovascular bundles. This led to the description of the modified &[prime]curtain dissection&[prime] in 2005. Recently interfascial dissection of the neurovascular bundles that is tension and cautery free was described. Recent advances on microdissection robotic platforms such as mini-balloon tissue dissection could render further understanding of the anatomy of the prostate (Kommu et al. J Endourol 2009).

Conclusions

Laparoscopic and robotic urological surgery has had a significant impact on our understanding of the prostate gland. This evolving understanding continues to redefine surgical practices towards optimised outcomes in oncological treatment, preservation of erectile function and maintenance of continence during radical prostatectomy.

Funding

None

Introduction

Introduction: Throughout centuries of publications, different names and varied implications have accompanied the use of the term female prostate, an otherwise small anatomic region in women. As a result, many deny the existence and functional role of the female prostate in women’s sexual health. In reviewing past medical literature, we came across reports of the existence of the female prostate from the early days of the Kama Sutra. Scholars then discussed the homologous female prostate as a distinct organ within the female pelvis. Similarly, in 300 BC Herophiles identified the prostate gland during his human dissections and claimed this organ to be an anatomical component of both male and female reproductive anatomy. In 1672 Reignier de Graaf is credited with the first anatomical depiction of prostatic tissue surrounding the mid-urethra in women. Three centuries later Grafenberg described the role of the female urethra and surrounding prostatic tissue in orgasm.

Methods

Methods: A literature search was performed using the keywords "female prostate", "Skene's gland", "peri-urethral gland", and "G-spot". Over 200 publications were found based on relevance. Categories for analysis included anatomy, physiology, embryology, pathology, neural innervation, adenomatous and cancerous changes, and orgasmic potential. _x000D_

Results

Results: More than 60 publications were included for review and analysis. Since 400 BCE scholars have proposed the existence of sexually sensitive homologous "female prostate" peri-urethral anterior vaginal wall tissue. Contemporary researchers have characterized “female prostate” exhibiting glandular and secretive elements identical to male prostate via immunohistochemical studies with prostate specific antigen (PSA), prostate specific acid phosphatase, androgen receptors, biochemical analyses of PSA and creatinine in female ejaculate as well as three-dimensional modelling and waxy casts. _x000D_

Conclusions

Conclusion: "Female prostate" is embryologically and physiologically identical to male prostate. In some women, stimulation of "female prostate" via the anterior vaginal wall results in orgasm, analogous to stimulation of the anterior wall of the rectum resulting in orgasm in some men. The female prostate is not simply an incidental, vestigial organ; injury during surgical procedures may have clinical consequences, as peri-urethral anterior vaginal wall tissue possesses neurally-mediated sexually functional attributes. Despite skepticism, its existence is supported by extensive, reliable contemporary evidence._x000D_

Funding

None

Introduction

Genitourinary organs have played a notorious role in both crime and legal sentencing throughout history. Criminal activities including adultery, rape, and child molestation have been met with legally enforced castration and penile amputation. We aimed to provide a comprehensive review of criminal punishment as it relates to urologic structures.

Methods

A Pubmed and Medline review of literature concerning criminal sentencing as it relates to urologic organs was completed. Further research was then conducted using various primary resources, periodicals and encyclopedias detailing those events.

Results

Throughout ancient cultures, sexual mutilation was an accepted punishment for many criminal activities. Chinese law in the Dynastic era included Five Punishments, all of which involved physical mutilation. One of them, termed Gong, was a penalty for promiscuity or adultery and involved the removal of the testicles and penile shaft. Penile amputation was also utilized as punishment for licentious behavior during the Japanese Heian period. Punitive genital mutilation, however, is by no means confined to ancient history. Currently, eight states allow for chemical and/or surgical castration of incarcerated persons seeking rehabilitation for child molestation. The requirements for castration include that the criminal request surgery, that informed consent is obtained, and that castration cannot be coerced via threats or inducements. Other countries are not so enlightened as to ask permission prior to castration. Indonesia recently enacted legislation allowing for castration of men convicted of rape despite objections from the Amnesty International. Occasionally, however, the crime involves genital mutilation and the punishment is withheld. In Thailand from 1973-1990s, over 100 assaults involving penile amputation were reported with only a hand full of prosecutions for those committing the acts. Most amputations resulted from wives of husbands who were abusing them or committing adultery. Many husbands never filed charges and for those who did the Thai court system most often sided with the female defendant.

Conclusions

While criminal acts involving removal of genitourinary structures have been reported for centuries, it is troubling that some legally approved urologic mutilations are still prevalent in society. Despite the objections of human rights organizations, castration continues to be a legal punishment across the globe, including within the United States.

Funding

None

Introduction

The post-World War II era witnessed a proliferation of atomic science and an intense interest in radiation hazards to astronauts and pilots in nuclear-powered aircrafts, troops in the fields, and workers in nuclear plants. This became the context for two controversial experiments on the effects of x-ray irradiation on male fertility using human prison inmates. The objective of this study is to review the science and ethics of the medical experimentation on prisoners. _x000D_

Methods

We reviewed primary scientific literature on the two radiation experiments and secondary sources from legal journals and government investigations. _x000D_

Results

Between 1963 to 1973, the Atomic Energy Commission sponsored two studies on the effects of x-ray irradiation on human testicular function using healthy prison inmates at the Washington and the Oregon State Penitentiary. The studies enrolled a total of 165 prisoners who received exposure of 7.5 to 600 rad of radiation to the testes. Inmates in both control and exposure groups underwent period testicular biopsies and weekly seminal fluid examinations to determine the radiation dose that causes azoospermia or complete sterility. Both studies found a transient complete elimination of sperm production at 50 rad. However, at as high as 400 rad exposure, significant return of sperm production was invariably seen. All men were encouraged to undergo vasectomy at the end of the study to prevent possibility of defective offspring; however, eight men refused and some went on to have children with genetic defects. _x000D_ _x000D_ Both studies would have been in violation of federal regulation on permissible medical research in prison population as they exist today. Major ethical issues include coercion and exploitation of prison subjects, informed consent, and financial incentives. Prisoners were not properly counseled on risk of testicular cancer from radiation, in fact, the term cancer was deliberately avoided in the informed consent process.

Conclusions

The Washington and Oregon prison experiments on radiation effects on male spermatogenesis and fertility confirmed profound effect of radiation on testicular function. The result of the studies formed the basis of current limit of radiation exposure and occupation hazard regulation. These two experiments are important case studies not only for their contribution to the urologic knowledge but also for highlighting the interface between science and ethics.

Funding

None

Introduction

During the 2016 Rio Summer Olympic Games, Caster Semenya participated in the 800m finals and won gold. Her win, while a personal accomplishment, also had historical implications. Seven years prior, questions began to be raised about her gender ultimately leading to her temporary ban from athletic competition while she underwent "sex verification testing." The sex-testing to which she was subjected had a historical precedent. This paper seeks to explore the historical narrative surrounding intersex disorders as the presented in the form of female athletic competition.

Methods

A literature review was conducted in PubMed which identified primary and secondary sources regarding "sex testing" and "femininity certificates." These sources were reviewed in order to evaluate the sociocultural context of sex testing among female athletes in international competition.

Results

Sex testing began in earnest in the 1950s with the mandatory sex testing of female athletes during the European Championships, although rumblings of questioning the ender of female athletes pre-dated the creation of this mandatory law. In the 1930s, as women became increasingly involved in athletic competition, women's bodies were scrutinized if they appeared too "male-like" or exhibited athletic exceptionalism. Early sprinters such as Dora Ratjen of Germany and Stella Walsh of Poland were driven away from the sport due to claims that they were in fact men. Once testing became official, it consisted of invasive physical examinations, heavily focused on the genitalia as women were asked to "parade nude before a panel of doctors." Often as a direct response to these athletic community's inquiries into their sexual identity, these female athletes, who were branded as male and termed "hermaphrodite" subsequently underwent surgical reassignment. While testing transitioned to include genetic and hormone testing, the results remained relatively inconclusive and significantly altered the lives of the women on whom they were conducted_x000D_ _x000D_

Conclusions

Historically, dominant performances by women on the international athletic stage called into question their gender identity. Invasive sex testing was performed and many of the individuals who were investigated would be identified as intersex today. Contemporary discussions of transgender identity add a new layer of complexity to examinations of the intersection of gender and athletic competition as transgender athletes made history in the 2016 Rio Olympic Games by competing without having undergone gender reassignment surgery.

Funding

None

Introduction

Hypospadias is one of the commonest genetic abnormalities of the male genital tract. _x000D_ It is nowadays well understood that abnormalities of the genital organs can lead to psychosocial and psychosexual complications._x000D_ This study aims to review whether this was also recognised in antiquity._x000D_

Methods

Modern and historical manuscripts were reviewed using paper and online resources such as JSTOR, Google Books and archive.org.

Results

Hypospadias was recognised in the early classical period. Aristotle in his De generatione animalium (4th century BC) describes 'instances of boys in whom the termination of the penis has not coincided with the passage through which the residue from the bladder passes out,- on this account they sit in order to pass water, and when the testes are drawn up they seem from a distance to have both male and female generative organs.'_x000D_ _x000D_ This highlights the early recognition that hypospadias could give rise to vague genitalia and have an impact on perceived gender stereotypes such as having to sit to pass water for boys._x000D_ _x000D_ Hypospadias may have also affected early Hellenic art. Laios et al propose that the 'Phallus Vulva' vase, a piece of Greek pottery dated circa 610BC which depicts a phallus with an hole at the base of the shaft, may have be the first representation of a penoscrotal hypospadias in art. _x000D_ _x000D_ _x000D_ Social impact:_x000D_ _x000D_ Diodoros Sulcus (1st century BC) in Fragmenta Libri XXXII describes the case of a Greek woman named Kallo who although married had always declined sexual intercourse. A genital infection finally caused her to seek the services of a pharmacist who, upon incising what appeared to be labial adhesions discovered a case of penoscrotal hypospadias. _x000D_ The marriage was dissolved and Kallo elected to change her name to the male Kallon and live in a male gender role. _x000D_ _x000D_ A further maritial case arose over a millennium later in Malta and may well be the first recorded urological cause for the annulment of marriage in modern legal literature. _x000D_ A woman named Mathia living in Medina brought legal action against her husband John Azzopardi in 1542 due to his inability to perform his 'natural manly duties'._x000D_ He was examined by two physicians who rather uncharitably described his penis as: 'inept or incapable and also useless for deflorating or perforating' due to a ventral hypospadias with chordee. The marriage was annulled._x000D_ _x000D_

Conclusions

_x000D_ There is evidence that even in antiquity hypospadias was recognized as a condition with a potential impact on both the personal and societal perceptions of gender roles, having sometimes devastating and life changing effects on the men affected by it_x000D_

Funding

None

Introduction

Through Michelangelo’s life and artwork we gain glimpses of the Italian artist’s condition or recurrent kidney stones. Our aim was to search through literature to gain a better understanding of his symptoms and how he was treated for urolithiasis.

Methods

A literature search was performed using PubMed and Google on Michelangelo Buonarroti and kidney stones.

Results

Michelangelo Buonarroti (1475-1564) was presumed to suffer from chronic illness throughout life. He had a history of recurrent kidney stones as well as gout later in life. In 1999, Eknoyan claimed that Michelangelo’s medical condition influenced his artwork. Eknoyan pointed out the painting, God Separating Earth from Waters, was drawn in the shape of a “bisected right kidney”. Perhaps it is the artwork which stimulates further interest in Michelangelo’s medical history. _x000D_ According to some authors, Michelangelo was diagnosed with kidney stones at age 75 in 1549 and was treated by Realdo Colombo. However, there is mention of symptoms and kidney problems prior to 1549. In The Life of Michelangelo, Condivi mentions “gravel in his urine” which may have preceded kidney stones. A Week in the Life of Michelangelo relates events from 1518-1526 where the artist kept records of the food he ate during the day as he was recommended to eat light meals to prevent stones. _x000D_ Most detailed accounts of Michelangelo’s condition come from letters written to his nephew. In March 1549, he complains of difficulties with urination, fever, and pain which keeps him up at night. A few days later, in another letter he mentions being told to drink “a certain kind of water” which leads to passing of his stones along with “thick white matter”. He continues to mention this “spring water from Vitterbo” as his treatment regimen and reports feeling better. While acknowledging the treatment, Michelangelo continues to pray and thank God in each of his letters which give us a glimpse of the importance of faith in his illness. Despite treatment, Michelangelo’s health worsened and he was diagnosed with gout in 1555. The development of gout raises suspicion that he was suffering from urate stones. This could be due to a congenital medical illness or as Wolf suggested in 2005 it could be acquired from injury to his kidneys due to lead exposure from lead-based paints and wine stored in lead containers.

Conclusions

While the literature is inconclusive on the cause of Michelangelo’s kidney stones, it appears that compounds found in the paint he used contributed to his health conditions, which later manifested in his artwork in the form of God emerging from a bisected kidney.

Funding

none

Introduction

Dr. Howard Pollack retired as a well-known pioneer of uroradiology. He originally trained as a Urologist, but a disabling accident forced him to make a career change to Radiology. Dr. Pollack capitalized on the career change and helped found the specialty of GU radiology in the USA.

Methods

Internet and historical archive review, as well as personal interviews with former residents and faculty

Results

A lifelong Philadelphian, Pollack graduated from Temple University for college and medical school, and then Episcopal Hospital, for urology residency. He initially worked as a military urologist, as Chief of Urology at the 1,100th U.S. Air Force Hospital and advisor to the Surgeon General&[prime]s office. On return to civilian life, Pollack had a prosaic career as a community urologist. In a freak accident at home, a glass injury severely injured his hands ,disabling him and ending his urologic career. Instead of surrendering to tragedy, at middle age he changed careers and retrained as a Radiologist. His true calling was radiology. He quickly became an academic specialist, by applying his urologic skills to radiology. First, as chairman and professor of radiology at Episcopal Hospital and then as founder of the division of uroradiology at the University of Pennsylvania in 1977. He codified the specialty by establishing the Uroradiology Club in 1966, The Society of Uroradiology in 1974 and The Journal of Urologic Radiology in 1979. His textbook, Clinical Urography has been the bible of uroradiology. He also helped invent the endorectal coil for prostate imaging, sonographic classification of renal masses, and developed and refined interventional procedures (six patented inventions). Dr. Pollack was also a renaissance man; an art and history buff, passionate detective novel reader, and accomplished jazz pianist, and life-long baseball fanatic and sports trivia master. He published several sports articles and was more proud of them then any academic manuscript. On retirement, he worked on a definitive guide to every sports museum and hall of fame in the USA. Ironically, he died of metastatic renal cell cancer.

Conclusions

Dr. Pollack&[prime]s life epitomized the saying &[Prime]I asked for health, that I may do great things. I was given infirmity, that I might do better things.&[Prime]

Funding

none

Introduction

Nephroblastoma has been described for over a century. We explored the man behind the eponym, advances in tumor biology, and its how its treatment has evolved since early descriptions.

Methods

Literature review of Wilms and nephroblastoma.

Results

The Man: Born in 1867, Carolus Maximilianus Wilhemus Wilms initially pursued pathology but later secured a position with the surgeon Trendelenburg. During this time, published a three-part monograph, the first of which described mixed renal tumors. He pioneered new approaches to prostatectomy, though his interests extended far beyond urology. During his chief surgeon appointment to a World War I army corps, he became septic after performing a tracheotomy on a prisoner of war with diptheria, dying in 1918. _x000D_ The Tumor: Despite the eponym, Wilms tumor was described before his monograph. Microscopically confirmed as cancer in the 1850s, the mixed histology was not described until 1872. Wilms explored it further, identifying connective tissue, smooth and striated muscle, and epithelium, and proposed an embryologic origin in 1899; he was granted the eponym in 1900. Later pathologists identified traits, such as anaplasia, that impact outcomes and fine-tuned the triphasic elements described by Wilms into blastemal, epithelial and stromal components. Its association with multiple syndromes and occasional familial tumors primed it for genetic insights. _x000D_ Its Treatment: Jessop performed the first successful nephrectomy for nephroblastoma in 1877. Although the boy died 9 months later, he was one of the few early patients to survive nephrectomy for Wilms tumor; there was a debate among the surgical community as to whether surgery was ever appropriate because of the high mortality rate. Survival remained abysmal well into the 20th century. Operative mortality decreased after 1932, but <25% remained alive for ≥2 years. The cure rate jumped to 47% in the 1940s, an improvement attributed to early vessel ligation and post-operative radiation. Survival dramatically increased again with the advent of chemotherapy for Wilms, first reported in 1960. In America (1969) and Europe (1971), multi-center research groups formed to elucidate the best treatments. The groups diverged on the timing of surgery and chemotherapy. Now in an era with improved survival, treatment goals include minimizing morbidity and following long term sequelae._x000D_

Conclusions

Max Wilms, a man of diverse interests who died a hero, happened upon a biologically fascinating tumor. Its treatment, well-described for over a century, continues to evolve as we identify ways of maximizing survival with the least morbidity.

Funding

None

Introduction

The early 20th century was a marked period of growth and expansion of the health care system that was closely followed on America's biggest stage, New York City. A major milestone was the creation of the world's first academic medical center in 1928; which combined The Squier Urological Clinic, Sloan Hospital for Women, the Vanderbilt Clinic, and Presbyterian Hospital with Columbia University.

Methods

University historical archives and internet search, and personal communications of former Urology faculty.

Results

The name J. Bentley Squier is not eponymous with any signs, symptoms, procedures or technique. Perhaps his most unique attribute was his short stature and a partially amputated thumb. Squier believed in surgical expediency and efficiency, best demonstrated by his suprapubic prostatectomy (which he championed over perineal prostatectomy); often completing the surgery ≤10 minutes; 12 minutes if with bladder stones.His small hands and partially amputated thumb were uniquely suited to a narrow pelvis and to core out the adenoma. He was quite the showman, awing audiences by emerging from the pelvis with the entire adenoma sitting atop his thumb like an apple on a stick. To create the world's first academic medical center, Squier moved his Urological clinic from Madison Avenue to a new 70 bed unit on the 10th floor of the new hospital. To do so, Squier raised $400,000 from his many devoted and wealthy patients. Squier was the Urologists to the stars; like world heavy weight boxing champ Gene Turney,and NY Times publishers Ochs and Sulzberger. The Clinic had its own operating and cystoscopy rooms, pathology and radiology departments, and library. In 1929, he established a 30-bed pediatric service in Babies Hospital. In 1935 he became Chair of Columbia&[prime]s first Urology Department. He was already an academic giant; as one of the founding fathers, President, Governor and Regent of the American College of Surgeons and President of The American Urological Society. Just like today's changing medical landscape, the 1930's were tough economic times - so the clinic targeted well-healed private patients by creating more private rooms, a $4 a day &[Prime]pay ward&[Prime], and reducing charity beds . Increasing &[Prime]fee for service&[Prime] payers kept the Clinic solvent. Squier was succeeded as Chair in 1939, leaving behind a world-renowned and profitable Urology Department. _x000D_ _x000D_

Conclusions

The world of urology surrounding Squier resembles many challenges faced today: hospital mergers and acquisitions and a changing medical and economic landscape. Squier was a Urologic giant.

Funding

None

Introduction

Ureteroscopy is one of the most commonly performed procedures in current urologic practice, although rigid ureteroscopy was unheard of until the very recent past. Its origins has direct New England ties. Although the first documented “ureteroscopy” is attributed to Hugh Hampton Young who performed inadvertent endoscopy of the ureter in a 2 month old child with posterior urethral valves, this 1929 report was essentially relegated to anecdote that lacked any practical application.50 years later, in a small New England town, diagnostic and therapeutic ureteroscopy were born with the first planned rigid ureteroscopy and the introduction of ureteroscopic-guided intervention.

Methods

A comprehensive search of Medline was undertaken to assess all published articles describing ureteroscopy prior to 1980. References of identified papers were also reviewed to identify the earliest published accounts of rigid ureteroscopy. Upon identifying the initial reported ureteroscopy, the author was interviewed to better understand the context surrounding the inception of ureteroscopy.

Results

The first report of planned rigid ureteroscopy was in 1977. The procedure was performed by Dr. Tobias M. Goodman at Westerly Hospital. Dr. Goodman attended Browne and Nichols school in Cambridge, MA, then matriculated to Harvard College where he was an accomplished scholar in Classic Languages. After graduating from residency at Boston Medical Center, he started solo practice in Westerly, RI. At the time, blind stone-basketing was standard practice, but he recounts unease with the imprecise nature of blind manipulation. Thirty years prior to the AUA recommendation against blind-basketing, he proposed to several patients an improved, directly visualized approach to management of ureteral pathology. With a reputation as a physician who “knew how to stay out of trouble,” his patients eagerly agreed. Using a pediatric cystoscope with a standard bridge and an 11Fr sheath, he accessed, visualized and fulgurated a distal ureteral tumor. He developed techniques for diagnostic ureteroscopy and stone extraction, publishing the first series of rigid ureteroscopy in 1977. He subsequently developed patents for a ureteroscope, a 3-way endoscopic valve and Uroshiol for treatment of bladder cancer. Since retirement, he has authored 2 non-medical books: Out of the Attic and Ancient purple. He still resides in Westerly, RI where he is a guest columnist for the Westerly Sun.

Conclusions

Dr Tobias Goodman is a urologic pioneer who serves as an example of the creative thinking that has allowed the dramatic progress we continue to enjoy.

Funding

none

Introduction

Dr. Joseph E Murray was born, raised and educated in Massachusetts, where he developed a passion for science and research. Through his training and military experience, he witnessed the mysteries of graft rejection, which ultimately put him on a trajectory to become the first surgeon to perform a living donor transplant. He single-handedly transformed the world of transplant medicine into what we practice today.

Methods

Information on Dr. Murray was obtained from a thorough review of his published works, the William P. Didusch Center for Urologic History, the Nobel Prize organization, and testimonials from close friends and colleagues.

Results

Dr. Murray was born April 1, 1919 in Milford, MA. From a young age, he had a passion for science. He attended Holy Cross College where he gave up sports in order to attend science labs. Staying close to home, he attended Harvard Medical School. After completing his internship at Peter Bent Brigham Hospital, he joined the Army where he met Colonel James Barrett Brown, Chief of Plastic Surgery at Valley Forge General Hospital in Pennsylvania. Together, they treated soldier's burns and were eye witnesses to the consistent rejection of skin grafts. They observed that the closer the genetic relationship between the donor and recipient, the slower the rate of rejection of the skin grafts. After leaving the military, Dr. Murray pursued research on this concept, working for years with a renal transplant team at Brigham. Then, in 1954, Dr. Murray had the opportunity to take his bench research to the bedside when identical twin Richard Herrick was hospitalized with life threatening chronic nephritis. Amid harsh criticism and skepticism, Dr. Murray and his team prepared for the first human kidney transplant, which they successfully performed on December 24, 1954. He would go on to perform the first successful transplant in a non-identical recipient and the first cadaver transplant.

Conclusions

Dr. Murray was awarded the Nobel Prize in 1990 and praised for his perseverance in the field at a time when his work was heavily criticized. In addition to his professional accomplishments, he was also a loving husband of 67 years, a father to 6 children and grandfather to 18 grandchildren. The work of Dr. Murray transformed the realm of transplant medicine and continues to give the gift of life to thousands of people to this day.

Funding

None

Introduction

The radical transformation of President Chester Alan Arthur, from a political &[Prime]spoilsman&[Prime] to civil service reformer could be linked to his fatal diagnosis of Bright&[prime]s disease (chronic kidney disease) early on in his presidency.

Methods

We completed a review of the literature on President Arthur&[prime]s life, with a focus on his transformation from a political &[prime]spoilsman&[Prime] to a political reformer. Did his renal parenchymal disease lead to his passing of the Pendelton Act, which legislated civil service reform? What was the reason behind his passing of radical civil service reform which combated the very system of patronage responsible for his rise to presidency?

Results

President Arthur became the 21st President of the United States in 1881 after James Garfield succumbed to an assassin&[prime]s bullet. Before being chosen as Garfield&[prime]s vice-president, Arthur was known as the consummate political insider during an era that was marked by political patronage or the &[prime]spoils&[prime] system. Thus, when Garfield died and Arthur assumed the presidential mantle, many considered him to have little interest in political reform. The etiology of Arthur&[prime]s transformation from insider to reformer is unclear, however, early on in his administration, Arthur learned that he had Bright&[prime]s disease, a progressive and, at that time, uniformly fatal form of renal parenchymal disease. While Arthur&[prime]s role as a political reformer could be ascribed to his impending mortality, the extent of Arthur&[prime]s uremia, which resulted from progression of his Bright&[prime]s disease, may have moderated his temperament, softened deliberations, and hastened his signing of the Pendleton Act into law. The few primary sources that are available portray a President who is mentally and physically unwell immediately before, during, and after the passage of the Pendleton Act. In other words, Arthur may have been too sick and tired to fight civil service reform and simply signed the Pendleton Act as the path of least resistance.

Conclusions

President Arthur&[prime]s motivation in signing The Pendleton Act remains unclear given his early history, but it is conceivable that the diagnosis and/or the effects of Bright&[prime]s disease contributed to his uncharacteristic action of signing into law such landmark legislation._x000D_

Funding

None

Introduction

Franz von Paula Gruithuisen lived a life of inquiry. Through opportunity bore out of service to his country of Austria he forged his way into the medical ranks. Through his favored relationships with royalty he was able to reach for the stars. An unbridled mind of inquiry - we sought to tell his story, where impossible dreams transcend space.

Methods

Information was obtained through original works, translated to English; as well as accounts of his personal life through German and Austrian historical works.

Results

Franz von Paula Gruithuisen was born March 19th, 1774 in Upper Bavaria. The son a falconer from Holland and a sculptor; it is no surprise that his life would be spent looking to the skies and marveled by stone. _x000D_ He took quickly to the study of medicine and treatment of the human body while living in Landsberg (modern Germany) serving as a Barber's Apprentice. At the age of 14 he volunteered for the Austrian Army to serve as an assistant of the Field Surgeon in the Austro-Turkish War. Upon completion of his service, Prince Karl Theodor took special interest in von Paula Gruituisen bringing him into his personal employment in 1792 and eventually sponsoring his scholarship at university. He received a magnitude of awards for his works. _x000D_ In March of 1813 he published his works, "Should one abandon the long-standing hope of one day being able to remove stones in the bladder by mechanical or chemical means?" thereby laying his foundation for the transurethral destruction and removal of bladder calculi. He had postulated that stone destruction could be achieved by a variety of methods: washing of the stone with water, mechanical crushing, chemical dissolving, and galvanic pulverization. He drew heavily from his works across the natural sciences. In 1813 he tested his method by passing a straight tube into the bladder for drilling. His illustrations and instruments would serve as the scaffolding for lithotists to follow._x000D_ In 1826 King Ludwig I of Bavaria nominated Dr. Gruithuisen as an Extraordinary Professor of Astronomy, leading to von Gruithuisen forgoing his medical endeavors in order to focus on his astrological research. Gruithuisen's Crater was named in honor of his dedication to the study the moon._x000D_

Conclusions

Franz von Paula Gruithuisen pioneering work in transurethral bladder stone destruction served as the ground work for generations of urologist who followed. With one foot on the earth and his eyes turned to the stars, he dreamed about what may lie beyond our world. His lifelong pursuit of investigation is one to be admired and emulated.

Funding

None

Introduction

The exquisite leadership and unmatched resolve of Sir Winston Churchill during the Second World War are known well beyond the borders of Britain. The adversities he overcame in the 1930’s and 1940’s have been extensively explored. However, one lesser known misfortune he faced earlier in life had a profound impact upon Mr. Churchill. The details surrounding this urologic traumatic event are herein examined, specifically with respect to the management his physicians selected. These medical decisions early in Mr. Churchill’s life were important for shaping the future of the Western World and the emergence of the ‘British Bulldog’.

Methods

A review of the literature was performed with Google Scholar to assess secondary sources pertinent to the early life of Sir Winston Churchill. Specifically, to further examine the urologic traumatic event that took place during Churchill’s late adolescence and how this clinical situation was managed.

Results

In the early winter of 1892, an 18 year old Winston Churchill was on holiday at the estate of his aunt in Bournemouth, England. While accompanied by his younger brother and a young cousin, the boys took up a game of chasing the older Churchill. Churchill found himself in the middle of a bridge straddling a ravine with a boy on either side. In the spirit of the game, he climbed over the railing of the bridge and pondered, “to plunge or not to plunge, that was the question!” He chose to plunge, and the slender firs he hoped would break his 29-foot fall did little to mitigate the traumatic results. It was 3 days before he regained consciousness and several weeks before he could climb from bed. He was diagnosed with a ‘kidney rupture’ as well as a concussion and right shoulder injury. The Churchill’s family physician, Dr. Robson Roose, as well as a London surgeon, Dr. John Rose, recommended 3 months of bed rest. Churchill’s recovery was prolonged and he stated, “for a year I looked at life round a corner.”

Conclusions

Kidneys are the 3rd most common solid organ to be damaged following blunt trauma, and renal lacerations are a common result of rapid deceleration. These injuries need operative intervention in less than 10% of cases, but those numbers are bolstered by 21st century imaging. In late 19th century Britain, without the use of modern imaging technology, these physicians selected the appropriate conservative treatment modality. If young Winston Churchill would have met an early demise, the fight against Nazi Germany may have ultimately had a different outcome.

Funding

none

Introduction

The Dornier HM3 Lithotripter is an extracorporeal shockwave lithotripsy (ESWL) machine that revolutionized treatment of urolithiasis. Over 10,000 patients have been treated by the HM3 at University of Virginia (UVA) from 1984-2016. Continued use of the HM3 is a testament to its efficacy in treating stones and the dedication of lithotripsy technicians maintaining the device. Due to exhaustion of spare parts, we can no longer maintain the machine, and it will be retired on 1 Jan 2017. To our knowledge, this is the last HM3 lithotripter at an academic center in the United States.

Methods

We conducted structured interviews of key personnel present during installation in 1984. Detailed records were available for the number of HM3 cases per year from 2007-2016. From 1984-2004, the number of cases were estimated based on the number of shocks administered. Shocks per case were estimated at 3,000. We reviewed literature comparing the HM3 to other lithotripters.

Results

Dr. Jay Y. Gillenwater acquired the HM3 for 1 million dollars in 1984. The HM3 was initially only available to a group of 4 urologists working with Dornier, although Dr. Gillenwater had contacted the company first. Despite strong resistance against UVA acquiring the lithotripter machine and funds to finance it, Dr. Gillenwater leveraged connections with congress to put pressure on the company to sell the machine. Installation was completed over a 6-month period finishing in July 1984. The first patients treated were Air Force One pilots rendered unable to fly due to stones. Initially, the HM3 had been used only on renal stones, but Gillenwater pioneered the safe and effective treatment of ureteral stones, changing FDA regulations to allow ureteral stone treatment. Case volume increased to a maximum of 19 patients per day as a result. Use of the lithotripter has declined with the advent of ureteroscopy (Figure). Randomized clinical trials and observational studies have established the HM3 as the most efficacious lithotripter ever used.

Conclusions

The HM3 at UVA successfully treated over 10,000 patients and continues to outperform later-generation lithotripters. It leaves a significant legacy and ends a storied period of stone treatment at UVA.

Funding

None

Introduction

To present some aspects of rare and unusual urogenital disorders, including congenital malformations and syndromes, sometimes occurring in eminent personalities or having been described by famous scientists.

Methods

The review of historical sources and biographies of famous sufferers and the study of modern medical literature about all these rare urogenital diseases.

Results

Penile deformities such as hypospadias (the most known representative was Henry II of France (1519-1559), suffering also from chordee) and epispadias (respectively the most known was the Byzantine Emperor Heraclius, (575-641)) were recorded mainly by historians because of the infertility consequences or the bizarre urination habits (Heraclius needed protective measures to avoid getting wet). Historians also were attracted by spectacular and dramatic urological emergencies, such as Fournier gangrene, known by the case of the prominent sufferer Herod 10 BC-44 AD). _x000D_ Referring to famous researchers, François Gigot de La Peyronie (1678-1747), founder of the Royal Academy of Surgery of France, described the homonymous disorder (1743), consisting of penile deformity due to induration of the corpora cavernosa of the penis, now also called Induratio Penis Plastica (IPP) is one of the extraordinary urogenital problems together with the strongly psychologically and non- physically induced syndromes Koro (Genital Retraction Syndrome) and Castration Anxiety (the latter described by Sigmund Freud(1856-1939)). Belief that genitals have disappear and fear of damage or loss of the penis characterize them both. Much of the research has been done on the two above topics, although still relevant today._x000D_

Conclusions

Rare and unusual urogenital disorders attract the attention as extraordinary events (called Mirabilia by historians), especially if occurring on famous or evil persons (as a divine punishment). Furthermore, publicity is given when the above abnormalities are described by eminent physicians.

Funding

NONE

Introduction

The Civil War marked a major turning point in American epidemiology and medicine. Regulations at the start of the Civil War required the senior medical officer of each hospital, post, regiment, or detachment, to make monthly reports to the Surgeon General of the sick and wounded, deaths, and discharges. Urologic infectious, benign and traumatic diagnoses were documented along with other diseases across geographic and racial divides. Using primary documents and epidemiologic data, we attempt to reconstruct the state of urologic disease among soldiers during the War. _x000D_

Methods

Primary documents from the UC Davis Blaisdell Civil War Medicine Collection including the epidemiological tables of sickness and mortality from the Medical and Surgical History of the War of the Rebellion by Surgeon General Joseph K. Barnes were analyzed. A non-systematic review of Pub Med was also conducted. _x000D_

Results

In addition to ushering in new paradigms for the military hospital system, trauma surgery, and anesthesia, the Civil War also brought about major improvements in the way diseases were categorized and recorded. Data from the Medical and Surgical History of the War of the Rebellion demonstrates a small but significant burden of genitourinary pathology in the troops across the Atlantic, Central and Pacific Regions. Among GU diagnoses, sexually transmitted infections including syphilis, gonorrhea and orchitis had the highest incidence, averaging 33, 43 and 6 annual cases per 1000 white troops. The incidence of GU pathology was similar between white and non-white troops, with the exception of venereal disease, which was reported more frequently in whites. Venereal disease had a higher incidence at the start and end of the war. Prostitution, which has been well documented, was a likely contributor to the spread of venereal disease. The incidence of stones, benign scrotal disease, testis tumors and urethral strictures was relatively low and stable over the course of the war; surprisingly, of all GU diagnoses, varicoceles were associated with the highest rates of discharge from service. In this pre-penicillin era, the most fatal diagnoses were syphilis and infectious nephritis and cystitis. As previously described by Herr, traumatic GU injuries were relatively uncommon, representing <1% of all battle wounds; however, about half of injuries to the bladder and kidney were fatal and these injuries were fraught with complications such as fistulae.

Conclusions

Urologic pathology played a small but significant role in the lives of soldiers during the Civil War._x000D_

Funding

none

Introduction

The men and women who invented the atomic bomb would be horrified at its worldwide proliferation. Foremost among those scientists was Leo Szilard (1898-1964), arguably the first physicist to conceptualize an uncontrolled nuclear chain reaction. Szilard possessed an uncanny ability to see what was coming, and in fact got out of Berlin in 1933, one day before the authorities there began restricting exit visas. Safely in London, he was puzzled by Lord Rutherford's pronouncement that the atom would never be harnessed as an energy source, and as an avid reader of science fiction, he wondered if an element could be found whose nuclei would each release 2 neutrons upon bombardment by a single neutron. Realizing the implications of this exponential reaction, he had the foresight to take out a patent on the idea, thus delaying nuclear research in Europe for years.

Methods

Newly arrived in the U.S., Szilard worked secretly with Enrico Fermi in Chicago to build the world's first nuclear reactor, and was instrumental in galvanizing both the American scientific community and the Roosevelt administration to mobilize hastily to produce a fission weapon before the Germans did, putting him into direct competition with his old mentor, Werner Heisenberg, who didn't like Hitler, but naturally wanted Germany to have the bomb.

Results

After the successful test of a plutonium implosion prototype in July 1945, Szilard reversed course 180 degrees, leading a group of renegade scientists opposed to the use of the bomb in warfare. With an Allied victory all but certain, he argued against using it on the Japanese, who did not have a nuclear weapons program. He feared the precedent of using the new technology, realizing this was a seminal moment for humanity. After the war, Szilard dedicated the rest of his life to seeking world peace and fostering better communication between nations, as well as embarking upon a second career in biophysics. The many "firsts" attributed to him also include the breeder reactor, a reactor cooling system (for which he collaborated with Albert Einstein), and the linear accelerator, which is essential in the modern delivery of radiation therapy.

Conclusions

Szilard's final challenge epitomized his outlook on life - diagnosed with bladder cancer at age 60 in Denver, where his wife was a professor, he got a second opinion in New York from Dr. Willet Whitmore, who recommended a radical cystectomy and ileal conduit. Always the maverick, Szilard declined Dr. Whitmore's advice and designed his own cobalt therapy, under the direction of Dr. James Nickson at Sloan-Kettering. He subsequently remained cancer-free for 4 years, until he died in his sleep from an MI.

Funding

None.

Introduction

Social media is a global phenomenon altering the way in which people interact. Its uses and reach have evolved beyond mere online networking to include and impact medicine. Reports show that 70-75% of US consumers look to the Internet for healthcare advice, of which 40% rely on responses from social sites. Social media allows for rapid communication, discussion, and dissemination of information to large groups of people. It also allows physicians to bring to the forefront important healthcare issues. Pediatric urology in particular is well suited to utilize social media as a unique way to touch base with younger patients, particularly in discussing sensitive topics such as testicular torsion. _x000D_ _x000D_ There is no reliable method to identify which patients may develop testicular torsion until the onset of symptoms. If the patient is unaware of the condition, there may be a delay in presentation and intervention. The TWIST (Testicular pain suddenly; Warning or take action for pain, swelling, or redness; Immediately tell an adult; See a doctor; Time is limited) campaign began in 2013 as a regional campaign in DE, PA, and FL to promote awareness of testicular torsion. When this topic was taught at school and discussed openly in the community, these patients were found to present earlier leading to a higher likelihood of testicular salvage. With the advent of social media, this campaign led to the first live tweet chat on testicular torsion._x000D_

Methods

A comprehensive literature review in PubMed was performed related to keywords "social media" and "urology". Additionally, informatics regarding the live tweet chat were also obtained.

Results

The first live chat on Twitter regarding testicular torsion took place on 6/15/2015. It was sponsored by Kids Health, Nemours, Urology Care Foundation, Young Men’s Health, and Men’s Health Network. Dr Rupal Gupta, medical editor at Kids Health, Dr Carlos Estrada from Boston Children’s Hospital, and Dr T. Ernesto Figueroa from Nemours/AI duPont Hospital for Children were the facilitators of the chat. The search tags included #khchat and #TesticularTorsion. It lasted one hour, and was joined by 90 people producing 660 tweets and 33,750,157 impressions on this subject. Throughout the chat, various questions were posed by Kids Health that were answered by the facilitators to provide information and generate discussion.

Conclusions

Social media provides an outlet to discuss significant healthcare topics and serves as a unique way to reach a younger audience. Tweet chats in particular are a successful way in pediatric urology to promote awareness of important topics.

Funding

None

Introduction

Urethral stricture is a prevalent and challenging urological condition. Management has evolved over the last century, specifically with the advent of oral mucosal grafts for urethroplasty. We review the history of urethral stricture treatment._x000D_

Methods

A literature search of medical texts, journal articles and historical texts was performed pertaining to history of urethral strictures. _x000D_

Results

Urethra originates from the Greek word ourein 'urinate'. Urethral stricture was first depicted in Hindoo scriptures (6th century BC). Susruta described in Ayurveda the treatment by means of graduated dilators of metal or wood. Ambrose Pare in his depictions of urethrotomy mentions 'A silver weir, sharp at the upper end, is to be passed in as far as the obstruction, then by oft thrusting it in and out, it may wear and make plain the resisting caruncles'. _x000D_ _x000D_ In 1894, Sapezho first used oral mucosa in urethroplasty. Humby revived the use in 1941. This landmark discovery revolutionized urethral surgery. Several modern innovations have since been described: staged repair (Johanson 1953), dorsal onlay (Barbagli 1996), ventral onlay (Morey, McAnnich 1996), dorsal inlay penile (Hayes and Malone1999), dorsal inlay bulbar (Asopa 2001), panurethral stricture management (Kulkarni 2000), nerve sparing and bulbospongiosus sparing bulbar reconstruction (Barbagli 2008), Enterourethroplasty (Mundy 2010), Non-transecting anastomotic urethroplasty (Mundy 2015). Over this period the perineal incision has evolved from a lamda to a midline incision._x000D_ _x000D_ Current advances include liquid mucosal grafts; tissue engineering and stem cells, which would halt the process of fibrosis and prevent stricture formation._x000D_ _x000D_ Posterior urethral injuries have traditionally been managed by anastomotic urethroplasty. Pierce 1962 performed total abdominal pubectomy. Paine & Coombs 1968 performed anastomotic urethroplasty after excision of scar by abdominal approach. 1973 Waterhouse developed abdominoperineal approach. 1976 Turner-Warwick used omental wrap for transpubic primary anastomosis. Webster & Goldwasser 1986 performed perineal anastomotic urethroplasty using inferior pubectomy. Kulkarni 2010 described etiology and management of posterior urethral injuries. _x000D_ _x000D_ Currently a progressive stepwise approach has been used for managing posterior urethral injuries. _x000D_

Conclusions

Management of urethral stricture patients has evolved over the last century. The use of oral mucosal grafts is still one the greatest advancements. As we continue to better understand urethral strictures, we hope to make even greater strides over the next decade._x000D_

Funding

none

Introduction

Acute ureteral stent encrustation (USE) is a commonly encountered problem that can increase stent morbidity and make stone treatment challenging. Previous research into USE has focused on the physical and biochemical properties of ureteral stents to decrease encrustation. To date, this research has proven generally unsuccessful. To our knowledge, no detailed data exists on individual patient characteristics of early stent encrusters. We sought to characterize this population in order to identify risk factors associated with acute USE.

Methods

An IRB approved prospective study was designed to identify patients with early USE, defined as a calcified stent identified within 3 months of stent placement. From June 2016 to October 2016 all patients with indwelling ureteral stents were screened. Patients with stent encrustation were identified. Demographic data, past medical history, indwelling time of stent, stent size, and stent manufacturer were collected. Additionally, at the time stent removal, urine analysis, urine culture, stent culture, stone culture, encrusted stent stone analysis, and ureteral stone analysis were obtained.

Results

Seventy-six consecutive patients undergoing ureteroscopy and stent placement were screened. 9.2% of cases demonstrated early USE. Average age of our cohort was 46 years old (STD 5.1) and 57% of patients were female. Urinary tract stones were found in the ureter (60%) and renal pelvis (40%). Average BMI was 26.2 (STD 6.3). No patient had identifiable metabolic stone disease. All patients had normal baseline renal function (GFR>60). The median indwelling stent time was 56 days (IQR 44-69 days). 57% of patients had a positive urine culture taken at time of stent removal. In 71% of patients, the major stone composition for USE and urinary tract stones was brushite (range 60-100%). Stone and calcified stent cultures were positive in 4 of 7 patients, but were never the same organism isolated in urine culture. Only 1 patient had an encrusted stent consistent with struvite. Furthermore, Streptococcus species were isolated in 50% of encrusted stent cultures. One patient had a positive stent culture with a negative concomitant urine culture.

Conclusions

In our series, the most common calcification associated with acute USE was brushite stones. Additionally, stone and calcified stent cultures were positive with organisms dissimilar from those isolated in the urine. Stone and calcified stent cultures should be obtained in this group of patients, principally if stent exchange or additional procedures are required.

Funding

None

Introduction

Medical expulsive therapy (MET) is frequently used for patients with ureteral stones who present to the emergency department (ED). Our goal was to develop and validate a nomogram to predict the probability stone passage on MET for ureteral stones.

Methods

We reviewed ED visits within our health system with an ICD-9 diagnosis of urolithiasis, an associated CT scan, and discharged on MET between 2010-2013. CT's were reviewed to confirm stone size, location, and associated hydronephrosis. The primary outcome was spontaneous stone passage within 90-days of initial ED visit. Patients with no documented follow up in our system were called to collect data on stone passage. A nomogram was developed using variables chosen for clinical and statistical significance and validated internally using a bootstrapping technique.

Results

1,424 ED visits met the inclusion criteria and of these, 1,146 (80.4%) had confirmed ureteral stones on CT. Patients lost to follow up and who were unreachable by phone were excluded, leaving 661 patients to build the final model. The median age was 50 years (IQR 38-59) with 419 (63.4%) males and a median stone size of 4.0 mm (IQR 3.0-5.2). A majority of patients, 422 (64%), spontaneously passed their stone while the remaining underwent a procedure. On univariable analysis, patients who passed stones tended to have smaller stones (3.6 mm vs 5.2 mm, p < 0.001), stones in the distal ureter (73% vs. 41%, p < 0.001), and significantly higher WBC counts (9.49 vs. 8.57, p < 0.001). There were no associations between age (49 vs. 50, p = 0.831) or gender (64% male vs. 62% male, p = 0.451) on stone passage. In the multivariable model, stone size (per 1 mm increase; OR 0.49, 95% CI 0.43-0.57, p < 0.001), stone location (p < 0.0001), a prior history of stone passage (OR 1.74, 95% CI 1.04 - 2.93, p = 0.036), and WBC count (per 1k/uL increase, OR 1.12, 95% CI 1.04-1.21, p = 0.001) were significantly associated with spontaneous stone passage. The model was validated internally (bootstrap-adjusted concordance index, 0.80) and demonstrated excellent calibration.

Conclusions

For patients presenting with ureteral stones in the ED amenable to observation, we have developed a model to predict the probability of stone passage. Early follow-up or intervention for patients with a low probability of stone passage could improve patient satisfaction and prevent costly ED returns.

Funding

None

Introduction

Patients generally prefer to avoid surgery for ureteral stones. The initial management decision is a leap of faith influenced by patient and physician experiences and preferences. We explore the impact of patient centered factors on initial decision making.

Methods

As an element of an ongoing quality improvement program, patients presenting to a subspecialty stone clinic after discharge from Emergency Department were identified. Inclusion criteria were unilateral ureteral stone <= 10mm on computed tomography and freedom from infection. Patients completed PROMIS pain intensity and pain interference symptom surveys (PROMIS score of 60 = 1 standard deviation above US population average). Patients participated in a shared decision making process between ureteroscopy and medical expulsive therapy (MET). Patients electing MET were followed for 90 days from initial clinic encounter in standardized fashion.

Results

Between 6/1/2014 and 5/31/2016, 686 patients met inclusion criteria consisting of 300 with proximal and 386 with distal ureteral stones. MET was elected by 483 (70.4%) patients including 164 (55%) proximal and 319 (82%) distal stone patients. Logistic regression demonstrates that patients with proximal stones, larger stone sizes, and higher PROMIS pain intensity were associated with choosing ureteroscopy (all p<0.001, Figure 1). Amongst patients electing MET, 61 (37.2%) proximal and 45 (14.1%) distal stone patients eventually had ureteroscopic stone clearance. Logistic regression demonstrates patients with proximal and larger stones were more likely to require surgery (all p<0.001, Figure 2).

Conclusions

As expected, patients with larger, more proximal stones were less likely to choose and be successful with stone passage. While of prognostic utility, these factors are beyond patient and physician control. However, outpatient symptom control after discharge from Emergency Department could be improved and may be an important opportunity to increase the number of patients attempting stone passage.

Funding

None

Introduction

We aimed to improve the care of patients who were discharged from our ED with ureteral stones by decreasing the time to definitive surgical treatment, reducing subsequent ED re-use, and minimizing the loss of follow-up after ED acute care, using a new model of care involving collaboration between the ED and Endourology Division.

Methods

Starting March 1, 2015, automated email notifications were sent from our ED about all patients who were discharged from the ED with a diagnosis of ureteral stones. Among them, we determined those eligible for early surgical intervention using prospectively determined criteria (stone size ? 5mm, persistent pain, signs of infection, or renal function deterioration) and an Endourology provider contacted eligible patient by phone to offer them early surgical intervention without an intervening clinic visit. We compared patients in the initial email intervention period with a control group who were discharged from the ED prior to initiation of the email program. We matched intervention and control patients 1:1 by stone size, location, and gender. We then fitted a Cox Regression model to examine for differences in time to surgery between two groups, which was our primary endpoint. In addition, we compared the groups in terms of the loss of follow-up and ED revisits. _x000D_

Results

We compiled a comparison group of total 72 patients who underwent the email intervention and standard care. The groups had comparable body mass index, previous stone history, and renal function (all p>0.20). The time to surgery was much shorter in the intervention compared to the control group (8 days vs. 29 days, respectively, p-value <0.001). The new intervention was also associated with decreased proportion of patients lost to follow up (8% vs. 42%, p-value =0.001) and returning to the ED (6% vs. 25%, p-value 0=0.02). After adjusting for baseline characteristics and surgeon, using the email intervention decreased the time to surgery by 5 times that of the control group (HR=4.9, p-value <0.0001)._x000D_ _x000D_

Conclusions

An automated email notification program following by a phone call to offer early surgical intervention improved the quality of care for patients with ureteral stones by decreasing the time from ED to surgery, reducing the patient care burden on the clinic, minimizing loss of follow-up, and reducing ED revisits.

Funding

none

Introduction

Follow-up imaging is recommended as follow up for patients who present to the emergency department with ureteral stones and colic, but it often omitted if patients report cessation of pain. The purpose of this study was to update a previous report of how often a patient’s ureteral colic will cease despite still having a stone obstructing the ureter.

Methods

Fifty-three patients evaluated in an emergency department for ureteral colic and diagnosed with an obstructing ureteral stone who subsequently had follow-up in the urology clinic were retrospective evaluated. Patients who described the cessation of pain 72 hours prior to their office visit and who had follow up imaging were included in the study.

Results

Fifty-three (53) patients were included in the study. Mean patient age was 49.7 years (SD 15.3), gender distribution was 36% female:64% male, and mean time between visits was 27.4 days (SD 37.5). All patients (100%) reported having no pain for at least 72 hours prior to follow-up appointment, while 12/53 patients (22.6%) still demonstrated an obstructing ureteral stone on follow up imaging. Mean stone axial diameter was not different for patients who had passed their stones versus those who had not (4.9 mm versus 5 mm, p=NS).

Conclusions

In this study of 53 patients,?22%?of patients with ureteral stones?whose?pain completely ceased still had obstructing stones lodged in the ureter?on follow up imaging. ?This demonstrates that in the short term, one cannot confidently assume that cessation of pain signifies stone passage.

Funding

none

Introduction

Classically, acute flank pain and renal colic in nephrolithiasis is attributed to the presence of hydronephrosis and distention of the renal capsule. Patients often present with stones and no collecting system dilation, however, creating a therapeutic dilemma for urologists. Given that the biophysical mechanisms of visceral flank pain are not well understood, we aimed to characterize predictors of renal colic among stone patients without hydronephrosis.

Methods

From October 2015 to May 2016, new stone patients at the University of California, San Francisco (UCSF) were prospectively enrolled into the Registry for Stones of the Kidneys and Ureter (ReSKU). This electronic medical record (EMR) based stone registry captures patient clinical and imaging data for research purposes. For this study, we identified all patients with imaging-confirmed upper tract urinary stones and absence of hydronephrosis based on ultrasound or cross-sectional computed tomography imaging. Data analysis was performed on STATA Version 14.1 to identify factors associated with flank pain.

Results

During the study period, 116 patients with nephrolithiasis and no hydronephrosis were identified. 62.7% (n=74) had no flank pain associated with an ipsilateral stone, while 35.6% (n=42) had flank pain with an ipsilateral stone. There were no statistically significant differences between patients with and without flank pain with respect to age (60.0±2.1 vs. 57.3±2.6 years old), gender (51 vs. 45% male), smoking history (28.2 vs. 32.4% smoker), drinking history (48.7 vs. 42.3% none), BMI (28.4±1.0 vs. 26.4±1.5), or stone burden (1.86±2.6 vs. 1.80±4.0 cm). For patients with flank pain, those with renal stones were more likely to have flank pain compared with patients with ureteral stones (78.7 vs. 21.4%, p=0.018, Pearson chi-squared test).

Conclusions

Stones in the renal pelvis or calyces are more likely to cause pain in patients without hydronephrosis when compared with ureteral stones. Alternate mechanisms for acute renal colic must exist beyond obstruction and renal capsule distension. Understanding these mechanisms is critical to developing effective treatments for a subgroup of difficult-to-treat patients and warrants additional study.

Funding

Funding support was provided by NIH R21-DK-109433 (TC) and NIH NIDDK K12-DK-07-006 (TC).

Introduction

The current gold standard for imaging evaluation of urinary stones is non-contrast CT (NCCT), although in recent years the concerns regarding repeated radiation doses has called into question the need for this modality in all cases. For this reason, plain abdominal radiography (KUB) is used by many urologists in a diagnostic and follow-up setting. Digital tomosynthesis (DT) is a novel imaging technique that produces a number of coronal images from a single tomographic sweep, creating high quality images with less radiation than low-dose NCCT. Our aim was to evaluate the added utility of DT to KUB for the identification of urinary stones.

Methods

Seven fresh cadavers with an intact genitourinary system and no history of nephrolithiasis were implanted with kidney and ureteral stones of known size and composition using endoscopic methods or a small ureterotomy. After stone implantation was completed, the cadavers were imaged with KUB and DT. Three blinded readers (2 urologists and 1 radiologist with experience in evaluating KUB/KUB-DT for stone disease) evaluated all sets of radiographs. Readers initially evaluated only KUB for the presence and location of calculi and recorded their responses. Readers then were instructed to add in tomogram images to their evaluation and re-record the presence and location of calculi to assess the possible value added by tomograms without changing their initial responses based on KUB only. Reference standard was established by consensus reading with a board-certified urologist and board-certified radiologist with 7 years of experience, neither of which served as a blinded reader on this study. Accuracy of stone detection and assessment of stone location was performed using an exact and nearest neighbor match to account for potential movement of stones after implantation as well as perception differences between readers as to nomenclature of stone location.

Results

A total of 59 stones were identified in the seven cadavers as part of the gold standard interpretation. Using KUB only with an exact and nearest neighbor match, Reader 1 accurately identified 45.7% (27/59 stones), Reader 2 identified 47.4% (28/59) stones, and Reader 3 identified 35.6% (21/59) stones. Using KUB-DT with an exact and nearest neighbor match, there was a statistically significant improvement in accuracy of stone detection (p <0.01 for all readers) as Reader 1 accurately identified 72.9% (43/59 stones), Reader 2 identified 62.7% (37/59) stones, and Reader 3 identified 66.1% (39/59) stones. Overall this was calculated as a 57% relative increase in stone detection. Of note, the number of false positives (suspected calculi based on reader assessment that were not present on gold standard reading) on KUB and KUB-DT was similar across both reading sessions (11 and 16 respectively, for all readers combined).

Conclusions

Addition of digital tomosynthesis to KUB leads to significant improvement in the detection of urinary calculi when compared to KUB alone without a concomitant significant increase in false positives. Further studies will determine the true cost and radiation savings associated with the use of this technology, but it appears to be a promising imaging modality for urinary stones and a possible alternative to NCCT in some settings.

Funding

General Electric

Introduction

Computed Tomography (CT) is a clinically established modality to evaluate suspected urinary stones. The maximum stone dimension in the axial reconstruction and stone location are often used to estimate the probability of spontaneous stone passage and potential likelihood of surgical intervention. However, the measured axial dimension of urinary stones can vary considerably owing to irregular shape, obliquity to the imaging plane, non-isotropic imaging voxels, interobserver variability, and volume averaging. This limits the reproducibility of axial stone measurements and the accuracy of predictions based upon maximum axial stone dimension. The present study compared the standard measures of stone size from axial images to those obtained using dedicated stone analysis software, which determined maximal stone dimensions in all planes.

Methods

Non-contrast-enhanced abdominal CT scans from 211 consecutive emergency department patients performed to evaluate flank were retrospectively evaluated. Radiological reports were reviewed for a diagnosis of urolithiasis, the maximum axial stone dimension, and stone location. Corresponding 1 mm thick images were analyzed using dedicated stone analysis software to compute the maximum linear dimension in any direction and stone volume. Descriptive outcomes are reported here (mean (SD)), comparing traditional maximum axial dimension and stone volume (assuming a spherical stone) to measurements made using dedicated software that performed 3D stone segmentation.

Results

A total of 228 stones were identified in 143 of the 211 patients. The mean maximum dimension in any direction computed by the software algorithm was 5.0 (3.2) mm, which was significantly higher than the mean maximum dimension of 3.9 (2.9) mm contained in the radiographic reports (p=0.0002). The actual stone volume computed by the algorithm based upon the true stone dimensions and shape was 52.8 (141.5) mm3, while the stone volume calculated assuming a spherical shape was 31.06 (102.16) mm3 (p=0.0628).

Conclusions

Using dedicated stone analysis software, maximal stone dimension in any plane and stone volume were significantly larger than traditional measurements made in the axial plane and the associated volume. Semi-automated 3D measurements of stone size hence may be more accurate and reproducible. Further studies are needed to determine if automated 3D stone size metrics offer improved and more reliable prediction of spontaneous stone passage.

Funding

Mayo Clinic Urolithiasis O'Brien Grant

Introduction

American Urological Association guidelines recommend a combination of ultrasound (US) and kidney, ureter, bladder film (KUB) for monitoring patients with known ureteral calculous disease. We implemented a protocol of KUB and US for patients with known renal and/or ureteral calculous disease to investigate the subsequent use of computed tomography (CT) imaging and 90-day outcomes.

Methods

We conducted a retrospective review of patients who presented in an outpatient setting with a known ICD-9 diagnosis of renal and/or ureteral calculous disease whose evaluation involved a request for CT imaging. Included patients presented between November 1, 2013 and May 31, 2014, were non-pregnant adults (>18 years old), and had no US or KUB within 60 days of CT imaging request. CT requests were sent to a specialty benefits management company (SBM), from which the data were obtained, and a third party payer. For CT imaging to be approved, the SBM required US or KUB within 60 days prior to CT imaging request. Two cohorts were evaluated: 1) approved initial CT (iCT) request and 2) redirected CT request to initial US or KUB (iUS/KUB). Requests for the iCT cohort were approved because providers attested to prior US or KUB within 60 days, while CT imaging requests for the iUS/KUB cohort were redirected because providers did not attest to prior US or KUB within 60 days. Subsequent 90-day outcomes were analyzed including need for further CT imaging, emergency department (ED) visits, and hospitalizations.

Results

A total of 1307 patients were evaluated. The iUS/KUB cohort (n=447) underwent a significantly lower percentage of CT scans compared to the iCT cohort (n=860) (43.8% vs. 52.1%, p<0.005). There were no significant differences between the iUS/KUB and iCT cohorts in subsequent ED visits (7.4% vs. 6.7%, p=0.67) or hospitalizations (13.6% vs. 15.0%, p=0.51).

Conclusions

The use of US or KUB for outpatients with known renal and/or ureteral calculous disease was associated with reduced utilization of CT imaging without significantly affecting 90-day ED visits or hospitalizations compared with patients undergoing CT alone. These results may contribute to reducing the effective dose of radiation delivered to patients and may optimize resource utilization while maintaining similar patient outcomes.

Funding

None

Introduction

Approximately half of 24-hour urine collections in prior studies have been found to be outside the accepted cutoffs with urinary creatinine to weight ratio. Our study objective was to evaluate the relationship between measured urinary creatinine and lean body mass calculated 24-hour creatinine excretion based to improve accuracy for the evaluation of 24-hour urine collection adequacy.

Methods

This was a retrospective evaluation of 24-hour urine collections for 1319 unique nephrolithiasis patients. An established formula (figure 1c) previously to estimate urinary creatinine based on lean body mass was applied all patients in our cohort (Yu et al). We divided our cohort into two equal partitions (training and validation datasets) using a random number generator. Linear regression was used to quantify the relationship between the calculated and measured urinary creatinine in our training dataset. We then applied this relationship to our validation dataset. Two standard deviations from the expected value was considered an &[Prime]abnormal&[Prime] 24-hour urine collection. This regression-based approach was then compared with the standard method of verifying 24-hour urine adequacy.

Results

As demonstrated in Figure 1 for the validation cohort, there was a strong relationship between expected 24-hour urine creatinine based on lean body mass and the measured urinary creatinine (r²=0.7, p<0.01), which was stronger than the relationship between measured urinary creatinine and weight (r²=0.5, p<0.01). Using the traditional metric of Cr/Kg, 38% of patients in our cohort were considered to have an inadequate 24-hour urine collection (Figure 1a), and there more dispersion among inadequate specimens. Using the regression model on the validation set (Figure 1b), 15% of specimens were considered inadequate, and the majority were due to under collection.

Conclusions

Urinary creatinine is more strongly correlated to an individuals muscle mass rather than body weight. Our regression model demonstrated the utility of a lean body mass based 24-hour creatinine estimator that improves the ability to determine the adequacy of a 24-hour urine collection.

Funding

Not applicable

Introduction

Prior studies have demonstrated links between uric acid stone risk and low urine pH, visceral fat area (VFA) and the ratio of visceral to subcutaneous adipose tissue (VFA%). Our objective was to assess the association of CT-based visceral obesity with 24-hour urine metabolic risk factors stone composition in kidney stone formers (KSF).

Methods

This is a retrospective analysis of 99 kidney stone formers who had CT imaging and 24-hour urine studies at our institution. For each patient, a single axial area measurement was obtained at L3-4 in females and L2-3 in males for visceral fat area (VFA) and subcutaneous fat area (SFA). Percentage of visceral fat was calculated with the formula VFA%=[VFA/(VFA+SFA)] X 100. From established data, a VFA > 186 cm² was considered elevated in terms of risk of nephrolithiasis. Patient demographics, serum chemistry, 24-hour urine parameters and stone composition were collected for each patient. Univariate analysis was performed to compare patients with normal and elevated VFA. Multivariate linear and logistic regression was performed to assess for variables associated with 24-hour urine parameters and stone composition. _x000D_ _x000D_

Results

Compared to patients with normal VFA, patients with high VFA were older (65 vs 51 yrs, p<0.0001), more obese (BMI 33.3 vs 28, p=0.02) and were male (70.7% vs 30%, p=0.001). They also had higher prevalence of HTN (81% vs 45%, p<0.0001), DM (31% vs 12.5%, p=0.003), CAD (32.8% vs 7.5%, p=0.003). Higher VFA was associated with higher urinary sodium (175 vs 157 mmol/d, p=0.036), lower urine pH (5.724 vs 6.478, p<0.0001), higher serum uric acid (6.6 vs 5.3, p=0.002), higher prevalence of uric acid stones (15.5% vs 2.5%, p=0.031), lower bone mineral density (146 vs 168 HU, p<0.0001) and larger stone volume (256 vs 67 mm³, p=0.009). Multivariate analysis revealed higher BMI (p=0.009), coronary artery disease (p=0.027) and lower 24-hour urine pH (p=0.001) correlated with elevated VFA. 24-hour urinary citrate (p=0.031) and higher VFA (p=0.048) correlated with uric acid stone formation. Linear regression demonstrated that a higher VFA% was associated with lower 24-hour urine pH (β-coefficient -0.574, p=<0.0001)

Conclusions

CT-based diagnosis of elevated visceral fat area is associated with lower 24-hour urinary pH and formation of uric acid calculi. Evaluation for visceral obesity may help identify patients best suited for alkalinization and dissolution therapy. _x000D_ _x000D_

Funding

none

Introduction

Greater body mass index (BMI) and type 2 diabetes mellitus are associated with kidney stone risk. Increased urinary excretion of oxalate (Uox) has been correlated to increasing BMI. Our objectives were to determine if this association is linked to hemoglobin A1C levels (A1C).

Methods

We retrospectively reviewed 1,428 twenty-four hour urine collections gathered from a single institution from 2004-2015 from two urologists. 665 unique non cystinuric adult stoneformers (SF) with complete data including BMI, age, gender, A1C levels, and Uox were then analyzed using ANOVA, Chi-squared, and linear regression analyses.

Results

Average age of SF was 49.9 years. 46% of SF were female. Average BMI was 29.2 (Underweight 1.4%, Normal weight 26.5%, Overweight 35.8%, Obese 27.7%, Morbidly Obese 8.6%). Greater BMI correlated with increased Uox (mg/d) (p≤0.0001, r=0.245) and remained significant for both males (p≤0.001, r=0.30) and females (p≤0.001, r=0.195). The positive correlation between BMI and Uox was also seen in both African American and Caucasian subjects (r=0.34, p=0.02 and r=0.20, p≤0.005). A significant positive correlation between A1C and Uox was demonstrated (r=0.24, p≤ 0.009).

Conclusions

Among SFs, there is a positive correlation between BMI and Uox as well as A1C and Uox. These relationships may explain associations between both obesity and diabetes and the development of kidney stones.

Funding

AUA Research Scholar

Introduction

Historically staghorn calculi have been thought of as infectious stones, made up primarily of magnesium ammonium phosphate or (struvite) stones. The American Urological Association (AUA) guidelines for management of staghorn calculi continue to state calcium oxalate or calcium phosphate stones as unlikely causes of staghorn calculi. We reviewed our institutions incidence of infectious and metabolic composition in large staghorn calculi

Methods

Medical records were retrospectively reviewed for patients who underwent percutaneous nephrolithotomy (PCNL) for complete staghorn calculus from 2010 to 2015. Stone analysis and charts were reviewed for demographics, surgical complications, preoperative urine results and outcomes compared to stone type. Primary outcome of the study was to identify stone composition in infectious and non-infectious cases

Results

217 PCNLs were completed at our institution between 2010-2015 for stones >2cm. 72 patients (75 kidneys) had large staghorn calculus that met our size criteria. 3 of these were excluded. Overall 28 (39%) of patients were found to have infection stones, either struvite or carbonate. 44(61%) stones were composed of metabolic based stones without any infectious composition. The primary compositions in the metabolic stone group were calcium phosphate (52%), Uric Acid (18%), calcium oxalate (18%), and cystine (12%). In patients with purely metabolic stones, 65% of patients with primarily calcium phosphate hydroxyapatite had positive pre-op urine cultures, while only 12.5% of patients with primary calcium oxalate stones had positive pre-op urine cultures. Preoperative urine cultures revealed Proteus present (4.5% vs 46.4%) for non-infectious and infectious stones. E. Coli was present in preoperative urine cultures (15.9% vs 3.5%) for non-infectious and infectious stones. Proteus was the most common bacteria in infectious stones, while E. Coli was most common with metabolic stones. Infectious stones were 3.2 times as likely to have at least a Clavien-Dindo Grade 1 complication as metabolic stones (p=0.017).

Conclusions

In our study more staghorn calculus were composed of metabolic stones than infectious stones. Calcium phosphate was the most common stone composition for staghorn calculi differing from historical reports of staghorn calculi being primarily infectious. Patients with calcium phosphate stones also had a high rate of positive urine cultures. More research is needed on the cause of this paradigm shift._x000D_ _x000D_

Funding

None

Introduction

Metabolic abnormalities are associated with an increased risk for renal calculi. However, no studies to date have investigated whether metabolic factors affect the formation or recurrence of adults with bladder calculi. We aim to characterize patients with primary bladder stones, with and without kidney stones, based on their clinical factors, 24-hour urine, and stone composition.

Methods

We reviewed the medical records of patients with primary bladder stones and classified them based on their history of kidney stones, metabolic factors, clinical characteristics, and stone composition. We used descriptive statistics, multivariate analysis, and one-way ANOVA to look at associations between these parameters.

Results

Final analysis included 50 men with mean age 64 years (range: 21 to 92). 90% of these patients had a history of concurrent kidney stones. Bladder stone only formers (N=10) were older, and had greater total stone burden, higher stone recurrence rates (40% versus 25%), more metabolic abnormalities, and significantly lower urine pH (p = 0.03) compared to the concomitant kidney stone formers (N=40). Bladder stone only formers had a higher incidence of uric acid (UA) composition compared to their counterparts (62.5% versus 31.5%). Further, UA stones in the bladder demonstrated lower pH (p = 0.02) while renal UA stones were associated with lower Cit24 (p = 0.03). Stone concordance in the concomitant kidney stone group was 55.6%.

Conclusions

Primary bladder stone formers had surprisingly high rates of kidney stone formation and higher incidence of recurrence than has been previously reported. Duly, bladder stone formation may pose a risk for recurrence of bladder and/or kidney stones. The metabolic profiles of both groups, regardless of whether they made only bladder stones or both bladder and kidney stones, were similar. Aggressive treatment for outlet obstruction and metabolic abnormalities may be warranted in patients who are bladder stone only or concomitant kidney stone formers. _x000D_ _x000D_

Funding

None

Introduction

Understanding patients&[prime] knowledge of risk factors for nephrolithiasis may aid in developing prevention programs. We assessed patients&[prime] perceptions of dietary risk factors affecting kidney stone formation, and determined independent predictors of patient awareness of factors promoting stone disease.

Methods

A 24-question survey assessing dietary knowledge of nephrolithiasis risk factors and demographic data was administered prospectively to 1,018 urology patients. Responses were summarized with frequency and percent. Statistical comparisons were made using chi-square tests. Multiple logistic regression was used to detect significant predictors of knowledge of stone disease risk.

Results

The study cohort was comprised of 70% (n=711) male patients; overall, only 25% (n=259) of participants responded that diet had an effect on kidney stone development. A total of 28% (n=284) reported a prior history of stone disease; of those respondents, 43% (n=122) believed that diet does effect kidney stone formation. The majority of respondents (58.9%, n=598) reported a willingness to make lifestyle changes aimed at lowering their stone risk. Participants who reported previous nephrolithiasis education were 35 times more likely to indicate that diet affects the risk of kidney stone formation. (Odds ratio [OR] =35.15, 95% confidence interval [CI] = 5.58, 221.25, p <0.01) (Table 1). Respondents who had received prior education were 6.25 times more likely to have been counseled by a urologist than by a primary care physician (OR = 6.25, 95%, CI = 1.1, 33.3, p <0.04).

Conclusions

Knowledge of dietary risk factors promoting nephrolithiasis was limited among our study population. However, the majority of patients expressed a willingness to make appropriate nutritional modifications. Respondents who received prior education on stone development appeared to be aware that diet affects the risk of kidney stone formation. Patients indicated that urologists typically deliver kidney stone related education. These results suggest a need for comprehensive teaching strategies for patients regarding the modifiable risk factors for nephrolithiasis.

Funding

none

Introduction

Recent epidemiologic studies have shown an increased prevalence of kidney stones in patients with metabolic syndrome (MetS). We have reported that the clustering of MetS traits is associated with greater severity of kidney stone disease (Am J Kidney Dis 61: 923-929, 2013). The aim of the present study is to clarify which stone composition is associated with MetS.

Methods

We retrospectively analyzed detailed clinical data from 30,448 patients with urolithiasis enrolled in the 6th Nationwide Survey on Urolithiasis in Japan conducted in 2005. Patients with lower urinary tract stones, struvite stones, cystine stones, other types of rare stone composition, unknown stone composition, or hyperparathyroidism and those younger than 15 years were excluded. According to the types of stone composition, the severity of kidney stone disease, assessed by the number of existing stones (single/multiple) and number of stone episodes (first time/recurrent), and abnormalities in urine constituents were examined by the number of MetS traits (obesity, hypertension, dyslipidemia, and diabetes).

Results

A total of 4,440 patients included in the final analyses were classified into four groups: calcium oxalate (CaOx) (n=3213), CaOx + calcium phosphate (CaP) (n=881), CaP (n=115), uric acid (UA) (n=191). The proportions of patients with recurrent and/or multiple stones significantly increased with the number of MetS traits only in patients with CaOx stone (P < 0.01, table 1). However, similar associations were not observed in patients with other stone compositions. In patients with CaOx stone, there was a significant and stepwise increase in the odds of recurrent and/or multiple stones after adjustment for age and sex. In patients with 3 or 4 MetS traits, the odds was 1.8-fold greater compared with patients with 0 traits (OR, 1.78; 95% CI, 1.29-2.42). In addition, the presence of MetS traits was associated with significantly increased odds of having hypercalciuria in patients with CaOx stone after adjustment for age and sex.

Conclusions

In patients with CaOx stone, MetS trait clustering is associated with greater severity of the disease and increased urinary calcium excretion. These results suggest that CaOx stone disease should be regarded as a systemic disorder linked to MetS.

Funding

none

Introduction

Prior studies have demonstrated that high daily temperatures increase the risk of kidney stone presentation, men produce more sweat than women, and people with public insurance have greater exposure to ambient temperatures than those with private insurance. The objective of this study was to determine differences in the temperature dependence of kidney stone presentation by sex, age, race, climate, and insurance type.

Methods

We performed a time series study of 132,597 patients who presented with kidney stones to Emergency Departments in South Carolina from 1996-2015. Conditional Poisson regression and distributed lag non-linear models were used to assess the association and lagged response between daily temperature and kidney stone presentation stratified by sex, age, insurance type, race, and climate zone.

Results

The relative risk for a daily temperature at the 99th percentile versus 10°C was 1.72 (95% CI 1.55, 1.91) for men and 1.15 (95% CI 1.01, 1.31) for women. This difference was greatest among patients 20-65 years old. The risk of kidney stone presentation following moderately high daily temperatures was less among patients living in warmer climates. The temperature-dependence of stone presentation did not differ by race or insurance type.

Conclusions

The risk of kidney stone presentation following high daily temperatures was substantially greater among men than women and similar between patients with public and private insurance, which suggests that the higher risk among men is due to the sexually dimorphic effect of heat on evaporative water loss rather than greater exposure to ambient temperature. The lower risk among patients living in warmer climates suggests that prolonged heat exposure may lead to adaptive responses that mitigate the effect of high temperatures on kidney stone presentation. These differences should be considered in secondary prevention strategies to increase fluid intake and projections of the effect of climate change on nephrolithiasis prevalence.

Funding

NIH K23DK106428

Introduction

It is commonly accepted that increased temperatures are associated with increased prevalence of kidney stone disease. When examining stone mapping studies of the United States, while some regions with high annual temperatures (the southeast) have higher kidney stone prevalence, other warm regions such as the southwest do not. One major climate difference between these two regions is annual precipitation and humidity. We sought to explore the associations among, temperature, precipitation and urinary stone disease.

Methods

We identified all patients who underwent ureteroscopy, percutaneous nephrolithotomy, or shock wave lithotripsy using data from the Office of Statewide Health Planning and Development (OSHPD) for the state of California (2010-2012). We calculated the rate of operative stone disease for each county based on the patient’s home zipcode. We obtained climate data for each county in California from the National Oceanic and Atmospheric Administration. We compared the rate of urinary stone surgeries, adjusted for county population, mean annual temperature, total number of days over 90 degrees, and the total annual precipitation.

Results

A total of 63,994 unique patients underwent stone procedures in California between 2010-2012. The mean county stone surgery rate was 1.77 cases per 1000 persons (range 0.05-3.16). In the lowest quartile of rainfall (less than 21 inches per year), the average stone surgery rate was 1.5 per 1000 persons. This was significantly less than 2.2 per 1000 persons in the regions with the highest quartile of rainfall (44 inches per year) (p<0.01). In fully-adjusted models, precipitation (0.019 increase in surgeries per 1000 persons per inch, p<0.01) and higher mean temperature (0.029 increase in surgeries per 1000 persons per degree, p<0.01) were associated with an increased rate of stone surgery (Figure 1). The effect of temperature was not significant unless precipitation was controlled for.

Conclusions

In the state of California, temperature alone is not associated with the county-level rate of stone surgery until precipitation is included in models. Our results appear to agree with the larger trends seen through the United States where the areas of highest stone prevalence have warm humid climates, and not warm arid, climates.

Funding

none

Introduction

Metabolic factors underlying the recent increase in stone prevalence are unknown. Herein, we evaluate metabolic risk factors in stone patients from two different decades, comparing changes in metabolic profiles of stone formers over time.

Methods

A retrospective review was performed of patients who underwent metabolic evaluation of urolithiasis with 24-hour urine collections at a single institution. There were 309 stone patients evaluated from 1988-1994 (group 1), and 229 patients from 2007-2010 (group 2). A comparison between both groups was performed to assess changes in demographics and metabolic profiles.

Results

Comparing group 1 to group 2, the male: female ratio decreased from 1.3:1 to 0.8:1, obese patients (BMI ≥ 30) increased from 22% to 35%, and patients ≥ 50 y increased from 29% to 47% (all p < .005). A greater percentage of patients had hypocitraturia in the recent cohort (46% to 60%, p = .001), with hypocitraturia significantly more frequent in obese patients (p = .005). Hyperoxaluria was also increased in group 2 compared to group 1 (23% to 30% p = .07), a finding that was significant in males (32% to 53%, p = .001).

Conclusions

Urolithiasis has increased in females, obese, and older patients, consistent with population based studies. We report a rising incidence of hypocitraturia and hyperoxaluria in the contemporary cohort, particularly in obese patients and in males, respectively. Further studies are needed to better characterize the metabolic changes corresponding to the increase in stone disease.

Funding

None

Introduction

Urolithiasis is a global health problem with a lifetime risk of up to 15 % in white men and 6 % in women and a recurrence rate of about 50 % in these patients. Over the last three decades (and since the introduction of shock wave lithotripsy [SWL]) there was a change in stone composition observable with an increasing prevalence of calcium phosphate stones. Calcium phosphate crystallization is driven by urinary calcium phosphate supersaturation which rises with elevated urine pH. A recent animal study revealed an increase in urine pH of SWL treated porcine kidneys. We therefore evaluated the effect of SWL on urine pH in the Swiss Kidney Stone Cohort (SKSC), a nationwide, multicenter, prospective register of kidney stone patients.

Methods

Of the first 350 patients enrolled in the SKSC register, 170 patients were eligible; 180 patients had to be excluded because of a short follow-up of <6 months, uric acid stone composition and/or incomplete data on previous stone treatment. The patients were grouped into 3 different groups according to their previous treatment: group A: SWL (n=49), group B: endourological treatment (n=67), group C: spontaneous stone passage (control group; n=54). The paired t-test and one-way ANOVA was used to compare the change of urine pH over time within and between the 3 different groups.

Results

44/170 (26%) patients were female. Median patient age was 47 years (range: 20-86). Stone composition was available in 57% of patients and did not significantly differ between the three groups (p=0.8). The median urine pH at first visit (≥ 4 weeks post stone passage or intervention) was slightly higher in group A after SWL as compared to the other two groups: pH 5.7 (IQR: 5.1-6.0) in group A; pH 5.5 (IQR: 5.0 -5.9) in group B; pH 5.5 (IQR: 5.1-6.0) in group C; p=0.4. There was a significant rise in urine pH at follow-up visit (3-6 months after initial visit) in group A after SWL treatment whereas no significant change was seen in the non-SWL groups B and C (median pH difference in groups A, B and C: +0.25, -0.19 and -0.005, respectively; p<0.001).

Conclusions

There was an increase in urine pH in patients who had undergone SWL while this was not seen in urinary stone patients who were treated endourologically or conservatively. This suggests that SWL may cause tubule cell injury that leads to functional disturbances such as changes of urine pH. Whether this has an impact on the rate of recurrences or future stone composition (increase in calcium phosphate content) will be explored in the further follow-up of these patients.

Funding

none

Introduction

Laser therapy has gained increasing acceptance as a relatively less invasive treatment for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE). The potassium-titanyl-phosphate (KTP) laser, as well known as GreenLight laser (PVP) has been recently tested in a numbers of clinical studies. However, clinical outcomes have been different and not always the same. Recently, it has been tested the BPH6 score as a reliable patient reported outcome (PROM) for the evaluation of patients who underwent BPE surgery. _x000D_ In this study we aimed to compare PVP vs. TURP regarding BPH6 outcomes at 12 months of follow-up in a matched pair analysis. _x000D_

Methods

From January 2014 to January 2016, we conducted a matched pair analysis on 220 patients to compare the efficacy and safety of PVP laser and bipolar TURP in terms of the composite BHP6 endpoint at 12 mo. A propensity score matching was performed to adjust for preoperative prostate volume, peak flow and international prostate symptoms score (IPSS). _x000D_ Patients with LUTS secondary to BPE and refractory to medical therapy underwent TURP of 180 W PVP. The BPH6 primary study endpoint is a composite of six elements that assess overall outcome including LUTS relief, recovery experience, erectile function, ejaculatory function, continence and safety. The final BPH6 responder endpoint is achieved if a participant meets all six of the criteria defined as follow: LUTS relief: reduction of >=30% in IPSS at 12 mo compared to baseline, Recovery experience: QoR VAS >=70 by 1 mo, reduction of <6 points for SHIM (Sexual Health Inventory For Men) compared to baseline during 12-mo follow-up, response to MSHQ-EjD (Male Sexual Health Questionnaire Short Form for assessing ejaculatory dysfunction) question 3 indicating emission of semen during 12-mo follow-up, ISI (Incontinence score index) of ?4 points at all follow-up intervals, no treatment-related adverse event greater than grade I on the Clavien-Dindo classification system at any time during the procedure or follow up. _x000D_ All data presented are given as mean ± standard deviation (SD). Statistical analysis was performed using the SPSS 19.0 statistical software package (SPSS Inc., Chicago, IL, USA). _x000D_

Results

After the matched paired-analysis, a total of 123 (55 TURP and 68 PVP) were analyzed. Participants were well matched between the study arms, with no statistically significant differences of prostate volume, peak flow and IPSS. When comparing both groups, the proportion of patients achieving the BPH6 recovery endpoint by 12 mo was 45.6% in the PVP group, which was significantly better than the rate in the TURP group (18.2%) (p=0.001). In particular, PVP group showed better BPH6 outcomes vs. regarding TURP regarding recovery (82.4% vs. 58.2%; p<0.05), ejaculatory function (58.8% vs. 34.5; p<0.05) and safety (94.1% vs. 78.2%; p<0.05). The TURP group showed greater catheterization time (4.67 vs. 1.25; p<0.01) while PVP showed greater recovery experience (77.35 vs. 68.73; <0.01). Postoperative Ejaculatory dysfunctions were observed in both groups, 58.8% in TURP and 34.5% in PVP group. _x000D_ No difference regarding LUTS reduction, erectile function and continence. In both groups surgery did not cause any adverse events that required surgical intervention or revision and reintervention for failure to cure did not occurred in 12mo follow up. The multivariate logistic regression analysis, adjusted for pre-operative variables, showed that PVP was independently associated with BPH6 recovery endpoint (odds ratio= 3.77 [95%CI 1.64-8.70]; p<0.01). _x000D_

Conclusions

This study sheds some light in support of PVP technology. The results prove that PVP of the prostate represents an effective and safe technique, combining minimal morbidity and significant advantages compared to TURP regarding BPH6 outcomes. In fact, this is the first study comparing those two techniques in terms of the composite BHP6 endpoint, a reliable tool that can easily applied to compare BPE surgery procedures.

Funding

None

Introduction

Pure bipolar plasma vaporization (BPV) has been established as low-morbidity alternative to conventional transurethral resection of the prostate (TURP). Low intra- and postoperative morbidity as well as excellent functional short-term results have been reported. However, long-term outcome is still lacking. The extent of prostate tissue removal, which impacts the durability of postoperative functional improvements, is also unknown after BPV. The aim of the present study was to investigate the long-term functional outcome and associated prostate volume changes following pure BPV of the prostate.

Methods

A consecutive series of 75 patients treated by pure BPV in a tertiary care academic center was prospectively investigated. Prostate volume was assessed using planimetric volumetry following transrectal 3D-ultrasound of the prostate. Prostate volume and clinical parameters were recorded preoperatively and regularly after BPV (after catheter removal, 6W, 6M, 1, 3 and 5Y).

Results

Median (interquartile range; IQR) preoperative prostate volume was 41 ml (26.8ml), IPSS 16 (10), QoL 4 (2), Qmax 10.1ml/s (8ml/s), PVR 91ml (140ml) and PSA 2.57ng/ml (3.5ng/ml). A significant relative prostate volume reduction (RVR) of 33.3% (IQR: 22.3%; p<0.001) was already detectable at the time of catheter removal. Relative volume reduction increased significantly up to 12M (6W: 45.9% (17.4%; p<0.001), 6M: 50.5% (16.1%; p<0.001) and 12M 52.2% (17.4%; p=0.014). After 12M the RVR remained stable with 50.6% (14.3%; p=0.58) after 3Y and 52.6% (14.1%; p=0.59) after 5Y. Postoperatively, all investigated clinical parameters improved significantly and remained stable during the 5Y follow-up [5Y results (IQR): IPSS: 3 (8), QoL: 1 (1), Qmax: 16.3ml/s (13.7ml/s), PVR 20ml (46.5ml)]. Median PSA reduction after 5Y was 55% (36.2%). During the observation period 9 urethral strictures (12%) were detected of which 7 were de novo strictures. Bladder neck incisions for postoperative bladder neck stenosis were performed in 6 patients (8%). Median prostate volume in these patients was 30.6ml (18.2ml). Re-resections for re-grown adenoma were not necessary.

Conclusions

Low intra- and postoperative morbidity in combination with excellent functional outcome and durable prostate volume reduction confirm the role of contemporary BPV as a minimally invasive alternative to conventional TURP. However, postoperative bladder neck stenoses appeared rather frequent after BPV and might be a procedure-specific drawback.

Funding

none

Introduction

To evaluate for the first time long-term outcomes after Photovaporization of the prostate (PVP) with the XPS Greenlight® laser (GL-XPS) in patients with symptomatic benign prostatic hyperplasia (BPH).

Methods

A prospective study was performed of all patients with symptomatic BPH who underwent GL-XPS vaporization at our institution between September 2010 and September 2012. Functional outcomes with at least 48 months of follow-up were evaluated by questionnaire. Long term rate of complications and /or reoperation were assessed. Prostate Specific Antigen(PSA) level was measured at 3, 12 and 48 months of follow up.

Results

The response rate of the long terms questionnaire was high, 82 %. 84 patients with full data were included. Mean follow-up was 57,4±6,8 months. Mean International Prostate Symptoms Score (IPSS) decreased significantly from 19,9±6,4 preoperatively to 8,2±5,7, 6,16±5,6, and 3,94±3,4 at 1, 3 and 12 months respectively. Mean IPPS remained stable at 5,9±5,8 after 48 months. The mean PSA level has reduced significantly, from 4,5±4,31ng/mL preoperatively. to 2,00±2,13ng/mL, 2,08±2,08ng/mL and 2,66±2,27ng/mL respectively at 3, 12 and 48 months. Urinary parameters were significantly improved. Mean Qmax increased from 9,6±3,8 mL/s preoperatively to 21,8±11,3 mL/s, 23,9±11,5mL/s at 1 and 3 months respectively and remained stable at 12 months at 25,2±9,2mL/s. The satisfaction rate was high, 88% after a mean follow-up of 57,4 months. Two patients required reoperation due to recurrent BPO and two others for bladder neck contracture.

Conclusions

PVP with the GL-XPS is a safe and effective laser technique at improving durably IPSS in patients with symptomatic BPH.

Funding

none

Introduction

The use of pre-operative transrectal ultrasound (TRUS) volume to size prostates prior to holmium laser enucleation of the prostate (HoLEP) surgery supports case selection during the steep learning curve. We have previously reported the use of TRUS volume as a predictive tool for enucleation and operating room (OR) times. For the established surgeon TRUS volumes can optimize theatre utilization. We represent our predicted versus actual enucleation and OR times to generate validated charts to use as an accurate predictive tool to enhance theatre utilization.

Methods

393 HoLEPs were undertaken with a 50 Watt (W) holmium laser (Auriga XL, Boston Scientific Inc., Richard Wolf Piranha Morcellator) by two HoLEP naive surgeons during their learning curve and subsequently. All patients underwent a TRUS volume pre-operatively (B-K Hawk 2102). Accurate enucleation time and total operating room (OR) time for a given TRUS volume were plotted to use as a predictive tool to enhance operating list scheduling. Using the predicted enucleation times from a original cohort of 253 cases linear regression modelling was undertaken to validate predictive enucleation & OR times with the actual enucleation times for our last 100 cases.

Results

Enucleation time and TRUS volume were plotted graphically for the 393 cases (blue shaded region) and compared to similar data previously plotted for our first 253 cases (red line). There was a clear improvement in enucleation and total operating room times indicating further improvement and accuracy in the predictive times for a given TRUS size as surgeon experience increases. This allows for the enhanced prediction of theatre time improving theatre utilization._x000D_

Conclusions

Validation of predictive TRUS volume graphs for enucleation time during HoLEP surgery can be used as a tool to enhance theatre utilization by individual surgeons. We recommend the use of this simple tool for units setting up a HoLEP service._x000D_

Funding

None

Introduction

Laser enucleation with morcellation (LEM) has gradually increased in popularity and is increasingly being performed in the United States. This database study compares early operative and post-operative outcomes following laser enucleation and laser photovaporization (LP).

Methods

All patients (2011-2014) that underwent LEM (CPT code 52649) or LP (CPT code 52648) were identified from the National Surgical Quality Improvement (NSQIP) Database. The two groups were compared for demographics, operative times, post-operative complications, readmission and re-operative rates. Data are represented as mean ± standard deviation (SD) or median (interquartile range). Logistic regression analysis was performed to account for confounders and a p value of <0.05 was considered significant.

Results

A total of 8,171 patients were identified. 14.5% (n=1187) had LEM and 84.5% (n=6984) had LP. The respective mean age group was 69.3±8.7 and 71.4±9.2 years in the LEM and LP groups. Race distribution (LEM/LP) was white (1007/5096), Black (71/338) and others (109/1150). The ASA distribution (1/2/3/4) was 47/646/466/28 in LEM and 228/3099/3356/298 in LP groups. The mean BMI was similar for the LEM and LP groups at 28.4 and 27.87, respectively. The number of cases performed during the years 2011, 2012, 2013, and 2014 were 135/291/372/389 in the LEM group and 1045/1562/2056/2321 in the LP group. A higher proportion of patients required general anesthesia ( 93.6% vs 84.3%) and were performed in an inpatient setting( 38.5% vs 17.4%) in LEM vs LP. The mean operative time was significantly longer in the LEM (106.7 vs 54.8 minutes, p=0.001) versus the LP groups. The mean length of stay after surgery was also longer (1.24 vs 0.67 days, p=0.0001) in the LEM group. The differences in the transfusion rates, urinary tract infections, re-operative and readmission rates are shown in Table 1.

Conclusions

Regarding patients undergoing LEM versus LP, a higher proportion of patients require inpatient admission and the operative time is significantly longer in the LEM group compared to the LP group. The transfusion rate is higher for LEM compared to LP, but readmission and re-operative rates are similar. LEM is a feasible and comparatively safe operation to LP.

Funding

None

Introduction

Studies comparing learning curves and outcomes after HoLEP compared to other endoscopic enucleation techniques are lacking. None have assessed the learning curve of Greelight Laser enucleation of the prostate (GreenLEP). The aim of this study was to compare the learning curves and the perioperative and early functional outcomes of GreenLEP to those of HoLEP

Methods

Data from the first 100 consecutive cases treated by GreenLEP and HoLEP by two surgeons were prospectively collected from dedicated databases and analysed retrospectively. En-bloc GreenLEP and two-lobar HoLEP enucleations were conducted using the GreenLight HPS™ 2090 laser and Lumenis™ Holmium laser. Patients’ characteristics, perioperative outcomes and functional outcomes after 1, 3 and 6 months were compared between groups.

Results

Total energy delivered and operative times were significantly shorter for GreenLEP (58 vs 110 kJ, p<0.0001; 60 vs 90 min, p<0.0001). Operative time reached a plateau after 30 procedures in each group. Length of catheterization and hospital stay were significantly shorter in the HoLEP group (2 vs 1 day, p<0.0001; 2 vs 1 day, p<0.0001). Postoperative complications were comparable between GreenLEP and HoLEP (19% vs 25%; p=0.13). There was a greater increase of Qmax at 3 months and a greater IPSS decrease at 1 month for GreenLEP, whereas decreases in IPSS and IPSS-Q8 at 6 months were greater for HoLEP. Transient stress urinary incontinence was comparable between both groups (6% vs 9% at 3 months; p=0.42). Pentafecta was achieved in four consecutive patients after the 18th and the 40th procedure in the Greenlep and HoLEP group respectively. Learning curves ranged from 14–30 cases for GreenLEP and 22–40 cases for HoLEP.

Conclusions

Learning curves of GreenLEP and HoLEP provided roughly similar peri-operative and short-term functional outcomes.

Funding

none

Introduction

The optimal management option for BPH/LUTS for prostates >80g is unclear. Theoretical advantages of GLEP include improved hemostasis due to the absorption spectrum of 532nm laser, better tissue handling due to the side-firing laser fiber, better visualization of the prostate capsule, and more versatility with concomitant vaporization. We study the safety and feasibility of en-bloc GLEP with prostate morcellation using a side-firing laser as a new technique for definitive management of symptomatic LUTS in patients with prostates >80g.

Methods

We performed a retrospective analysis of 82 consecutive patients who underwent GLEP from 9/2014 to 8/2016. Primary outcomes were AUA symptom score, maximum flow rate, and post-void residual volume. Secondary outcomes were quality of life score, IIEF-5 score, and PSA._x000D_ _x000D_ Technique: Using 26 Fr Wolf resectoscope and side-firing 2090 GreenLight laser fiber, we incise the apical mucosa, separating the prostate from the external sphincter. Using the laser energy and blunt dissection, prostate lobes are enucleated on either side of the verumontanum. Dissection is carried out circumferentially until the bladder neck is reached. Hemostasis is achieved with laser coagulation. Once the enucleated adenoma is pushed into the bladder, morcellation is completed using the Wolf Piranha morcellator._x000D_

Results

Mean age was 71 years, with 47.6% of patients on anticoagulation and/or antiplatelet therapy. Mean procedure time was 140 min ±55. The mean preoperative prostate size was 145ml ±86.46, with a mean size morcellated volume of 66mL ± 54. 75% of patients were discharged home on postoperative day (POD) 1 and 75% of patients had catheters removed by POD2. Primary and secondary outcomes can be found in Table 1, with statistically significant improvement in all parameters (p<0.05) except IIEF-5, which demonstrated no change. Complication rates included 1.2% blood transfusion, 6.1% clot retention, 4.9% urinary tract infection, and 13.4% stress urinary incontinence. The majority of patients regained continence at later follow-up. There was no incidence of urethral stricture, capsular perforation, bladder or ureteral injury.

Conclusions

In experienced hands, GLEP is a safe and feasible option for management of large prostates.

Funding

None

Introduction

When a man with surveillance-appropriate low risk prostate cancer (PCa) has significantly bothersome BPH in a large gland, this typically tips the scales towards either radical prostatectomy or radiation therapy. However this presumes the PCa is the more threatening of his coexisting conditions. Incidentally discovered (T1a/b) PCa following Holmium Laser Enucleation of the Prostate (HoLEP) is a well known phenomenon. However, performing HoLEP in the setting of a PCa harboring gland has been underexplored. Herein, we describe outcomes of HoLEP in a select cohort of patients with significant LUTS, and known low risk PCa._x000D_

Methods

Data were collected retrospectively on patients undergoing HoLEP by a single surgeon. A select group of well informed patients with large symptomatic glands and low risk cancer were carefully counseled that HoLEP was an option to address the obstructive BPH, would unpredictably remove the cancer (all, part, or none), emphasizing they were not undergoing a cancer operation, and that HoLEP would be followed by continued surveillance. Pre- and post-operative clinical factors, and operative and hospital stay data were collected.

Results

In total, 7 men were included. All men had Gleason 3+3 cancer in at most 20% of at most 3 cores on biopsy. Other preop characteristics are described in Table 1. Mean tissue removed was 48.8g. No patients required transfusion or reoperation. Median length of hospital stay was 24.5 hours; median length of catheterization was 19 hours. On final pathology, 3 of 7 of patients had cancer in the specimen, all of which were Gleason 3+3. At f/u, all flow rates improved, PVR improved or remained low, and PSA significantly decreased in all patients (Table 1). No patient have developed stricture, bladder neck contracture, incontinence, or required reoperation. Median f/u time was 4 months (range 4-24 months). Notably, 2 patients had prostate MRI within 2 years of HoLEP, neither of which showed suspicion for PCa.

Conclusions

We have offered HoLEP judiciously to select patients on surveillance for low risk PCa and significant symptomatic BPH, a complex and increasingly common scenario, with acceptable short term outcomes. Further investigations into long-term cancer-specific outcomes, as well as strategies for continued surveillance, will be crucial in order to further evaluate and refine this new approach.

Funding

None

Introduction

To evaluate the safety and short-term outcomes of photoselective vaporization of the prostate using GreenLight XPS in treatment of high medical risk men. _x000D_

Methods

A multicenter retrospective analysis of 941 men who underwent photoselective vaporization of the prostate between August 2010 and August 2014 was performed. Patients were considered high medical risk if they had an American Society of Anesthesiologists physical status score >= 3. Postoperative adverse events, unexpected postoperative medical provider visits after intervention, and functional urinary outcomes were examined. _x000D_

Results

High medical risk men (n=273) were older (mean age 72.3 +/- 8.1 vs. 67.1 +/- 9 years, p < 0.01), had larger prostate volume (82.8 +/- 48.2 vs. 73.7 +/- 49.4 g, p < 0.01), and were more likely to be on anticoagulant and antiplatelet medications (all p < 0.01). Moreover, overall operative time (65 +/- 35.1 vs. 53.9 +/- 24.9 min), energy delivered (313.4 +/- 207 vs. 258 +/- 164 KJ), and energy density used (4.2 +/- 3.8 vs. 3.8 +/- 3 KJ/g) were greater in the high medical risk group (all p < 0.05). Although high medical risk men were more often treated in a hospital setting (p < 0.01), there were no differences in intraoperative adverse events. Both groups had sustained improvements from baseline for all urinary functional outcomes at six months. Regarding safety, the two groups had comparable 90-day Clavien-Dindo complication rates, number of urgent care visits, and number of outpatient consultations. High medical risk men, however, had more hospital readmissions within 90-day post-surgery (3.7% vs. 1.3% [p = 0.04])._x000D_

Conclusions

Despite older age, comorbidities, and higher use of anticoagulants, HMR men (ASA-PS 3/4) who undergo GL-XPS experience postoperative complications similar to healthier men (ASA-PS 1/2) in short term follow-up in addition to symptom improvement. GL-XPS produces safe and effective short-term outcomes in patients with multiple comorbidities. _x000D_

Funding

Boston Scientific Corporation

Introduction

HoLEP (Holmium Laser Enucleation of the Prostate) is a safe and effective procedure for BPO treatment. Six years ago we modified the traditional 3-lobe technique into the so-called en-bloc no-touch approach, characterized by the enucleation of the adenoma in one single horshoe-like piece (en-bloc), largely exploiting the vaporizing plasma bubble generated around the tip of the laser fiber at a short distance from the tissue (no-touch). After more than 250 procedures with the 100-120W holmium laser device, in 2015 we chose to apply a low-power approach to deliver less energy to the capsular plane, and possibly minimize postoperative dysuria. The aim of the present work was to assess the feasibility of the low-power approach, and to compare its outcomes in terms of safety and efficacy with those of the traditional high-power HoLEP.

Methods

316 patients suffering from BPO (any prostate volume, normal PSA, Qmax <15 ml/sec, IPSS>10, PVR <300 cc) underwent en-bloc no-touch HoLEP in our Department. From January 2012 to May 2015 214 consecutive patients underwent high-power HoLEP (group 1) with the 100-120W Versapulse holmium laser (Lumenis), 2J energy setting, 50 Hz, 100W power. From June 2015 to June 2016 102 consecutive patients underwent low-power HoLEP (group 2) with the 120W Versapulse holmium laser (Lumenis) for the first 20 patients, then the 50W Auriga XL holmium laser device (Boston Scientific), both 2.2J energy setting, 18 Hz frequency, long pulse length, almost 40W power. Patients demographics and clinical data were prospectively registered. Data were correlated using the Pearson correlation test.

Results

Mean age (69.4 years +/- 7.5 d.s. vs. 67.7 years +/- 8 d.s.) and adenoma weight (55 g +/- 39 d.s. vs. 46 +/- 36 d.s.) were similar in both groups. Energy used in Group 2 (53 kJ +/- 23 d.s.) was 1/3 less than in Group 1 (83.5 kJ +/- 32 d.s.). Enucleation time (31 min +/- 13 vs. 27.5 +/- 15), efficiency (1.64 g/min +/- 0.8 vs. 1.7 +/- 1) and morcellation time (9 min +/- 7.6 vs. 7.7 +/- 7.1) were equivalent. Pre- and postoperative IPSS (pre: 22 +/- 2.4 d.s. vs. 22 +/- 7 d.s.; post: 6.5 +/- 5 d.s. vs. 7.8 +/- 5 d.s.), incidence of postoperative bleeding (no blood transfusions)(4.2% vs. 3%) and recatheterizations (4.2% vs. 3%) were similar. Long-lasting incontinences of variable entity (mainly mild) were similar (1.4% vs. 1.6%), as well as the incidence of postoperative dysuria (10%) at 3-month follow up.

Conclusions

Low-power en-bloc no-touch HoLEP is feasible, safe and effective as the high-power approach, in the hands of experienced operators, being energy consumption reduced by nearly one third.

Funding

None

Introduction

HoLEP (Holmium Laser Enucleation of the Prostate) is a safe and effective procedure for BPO treatment. Six years ago we modified the traditional 3-lobe technique into the so-called en-bloc no-touch approach, characterized by the enucleation of the adenoma in one single horshoe-like piece, exploiting the vaporizing effects of the plasma bubble generated around the tip of the laser fiber at a short distance from the tissue. Transient storage symptoms, mostly resolving spontaneously or with medical therapies within 1-3 months, are described among the early complications in 9-59% of patients who underwent HoLEP, and have been correlated also with energy consumption. The aim of the present study was to determine whether postoperative dysuria is somehow influenced by the use of a low-power approach rather than of a high-power one.

Methods

316 patients suffering from BPO (any prostate volume, normal PSA, Qmax <15 ml/sec, IPSS>10, PVR <300 cc) underwent en-bloc no-touch HoLEP in our Department. From January 2012 to May 2015 214 consecutive patients underwent high-power HoLEP (group 1) with the 100-120W Versapulse holmium laser (Lumenis), 2J energy setting, 50 Hz, 100W power. From June 2015 to June 2016 102 consecutive patients underwent low-power HoLEP (group 2) for the first 20 cases with the Versapulse holmium laser (Lumenis), then the 50W Auriga XL holmium laser device (Boston Scientific), both 2.2J energy setting, 18 Hz frequency, long pulse length, almost 40W power. Patients demographics and clinical data were prospectively registered. IPSS questionnaires were self-administered before surgery and at 3-month follow up, VAS evaluation 1 month after surgery.

Results

Age (range 51-87 years) and adenoma weight (range 10-200 grams) were similar in the two groups. Mean energy employed for enucleation was 83.5 kJ +/- 32 d.s. for group 1, 53.4 kJ +/- 23 d.s. for group 2 (p<0.01), with a kJ/g ratio 2 +/- 1 vs. 1.5 +/- 0.8. Mean enucleation time was equivalent (31 min +/- 13 d.s. vs. 27.5 min +/- 11 d.s.), mean enucleation efficiency too (1.64 g/min +/- 0.8 d.s. vs. 1.7 g/min +/- 1 d.s.). Pre- and postoperative IPSS were similar (pre: 22 +/- 2.4 d.s. vs. 22 +/- 7 d.s.; post: 6.5 +/- 5 d.s. vs. 7.8 +/- 5 d.s.). Postoperative dysuria had the same incidence (10%), but in group 2 mean VAS evaluation at 1-month follow up was significantly better (6.2 +/- 1.5 d.s. in group 1, 2.4 +/- 3 d.s. in group 2).

Conclusions

Low-power en-bloc no-touch HoLEP uses less energy than the high-power approach, with reduced kJ/g ratio and similar postoperative dysuria (10%), being intensity and duration of the storage symptoms reduced.

Funding

None

Introduction

Intravesical prostatic protrusion (IPP) has been known as a predictor of efficacy not only for medical treatment such as alpha 1 blocker and dutasteride, but also for holmium laser enucleation of the prostate (HoLEP). However, the IPP is considered not the same in its shape because middle lobe and/or lateral lobes can protrude into bladder. Here, we evaluated the shape of IPP by cystoscopy and analyzed the outcome.

Methods

We reviewed charts of patients who had undergone HoLEP in Kyoto University Hospital from January 2006 to June 2016. Among 222 cases, 157 cases were evaluable for IPSS, uroflowmetry, IPP and its shape by preoperative flexible cystoscopy in outpatient clinic. IPP was classified into 5 groups: A, no protrusion; B, middle lobe only; C, lateral lobe only; D, bilateral lobe; E, B+C or B+D. Paired match analysis with similar IPP and other parameters was performed between the group with middle lobe protrusion (B+E, n=33) and the one without it (C+D, n=33).

Results

Table 1 shows the number of patients, age, score of total IPSS, QOL score, Qmax and IPP in the five groups. The group A (no protrusion) had a significantly higher Qmax than other groups. Groups with middle lobe protrusion (B or E) had a better tendency in changes in total IPSS score and Qmax. Paired match analysis shown in Table 2 demonstrated that the group with middle lobe protrusion had a significantly greater improvement of total IPSS score than the one without it (-16.6 vs. -10.8. p<0.01). Among them with less than 16 mm of IPP, all of patients with middle lobe protrusion improved IPSS, while only 76.5% (13/ 16) of patients without it were improved.

Conclusions

Patients with middle lobe protrusion had a greater improvement of IPSS in HoLEP than those having similar length of IPP without middle lobe protrusion. IPP should be clinically divided into two groups at least.

Funding

none

Introduction

Techniques of Prostatic Adenoma Enucleation by variety of energy sources are commonly practiced for surgical treatment of Obstructive BPH. We compare our short term results of Holmium Laser Enucleation ( HoLEP ) and Bipolar Enucleation ( PKEP/TUEB) in a prospective Randomized trial.

Methods

Between August’15 and April’16, a total of 98 patients with Obtructive BPH were treated and prospectively analysed at our center. A computerized randomization schedule was used. HolEP was done in 52 and Bipolar Enucleation was done in 46 patients. All Patients were evaluated by IPSS, Maximum Flow Rates ( Qmax), Transrectal Ultrasound Guided Prostate Volume(PV), Post Void Residue(PVR) and PSA. 100 W Holmium Laser and Plasmakinetic Bipolar energy by Spatula/Button Electrode was used for enucleation by single surgeon. Primary end points were IPSS and Qmax, secondary being reduction in PVR and PSA. Intraoperative and Immediate postoperative data like OR Time, Blood Loss, Irrigation Volume, Catherization/hospitalization time were compared between two groups.

Results

Pre-operative Demographics in both groups were comparable including Prostate Volume, HolEP ( 58± 8.2gms) versus Bipolar Enucleation _x000D_ ( 56.5±6.8 gms) p value being >0.05. Primary and secondary end points were comparable for both groups (p>.001). Blood loss in HolEP was marginally superior to Bipolar Enucleation ( 36±8.5 ml versus 68.5±7ml respectively, p=0.123). There was no significant difference in other parameters in both groups. OR time (34.5 versus 37 minutes) Catheterisation time ( 2.8 versus 3.1 days), Irrigation Volume (16.9 L versus 17.6 L), Hospital Stay ( 3.4 versus 3.9 days). One patient had prolonged hematuria, without requiring any intervention in bipolar group and two patients in each group had SUI lasting 3-4 weeks. There was no statistically significant difference in Primary and secondary end points in both groups at 1, 3 and 6 month follow-up.

Conclusions

Endoscopic Enucleation is effective irrespective of Energy source. Mean Prostate volume in our study was suggestive of Medium size Obstructive BPH, where, Bipolar Enucleation of Prostate was found to be equally efficacious compared with HoLEP in Short term follow-up. However, long term follow-up results in larger Prostate Volume remains to be seen.

Funding

None.

Introduction

Transient urinary incontinence may occur in up to 44% of patients after holmium laser enucleation of the prostate (HoLEP). However, there are few published data concerning the factors associated with de novo urinary incontinence (UI). The aim of this study was to investigate the associated factors of de novo UI after HoLEP.

Methods

Our study included 141 patients who underwent HoLEP. Enrolled patients were divided into two groups according to the presence of UI. Independent t test was used to compare between two groups. Logistic regression was performed to analyze a correlation between de novo UI and other factors such as age, prostate volume, retrieved tissue weight, operative time, and the first post-void residual (PVR) urine volume immediately after removing postoperative urethral catheter. Urethral catheter was removed after bladder instillation with a 200 ml normal saline via urethral catheter, and PVR urine volume was estimated immediately after the first postoperative self-voiding. All definitions of UI corresponded to recommendations of the International Continence Society.

Results

After HoLEP, 44 patients (31.2%) had de novo UI, most of which resolved within 1-6 months; 34 had stress UI, 6 had urgency UI, and 4 had mixed UI. Age and PVR urine volume were significantly higher in UI group than non-UI group (75.09 ± 6.82 vs 72.01 ± 8.04 years; P = 0.029, 81.88 ± 67.13 vs 30.15 ± 23.56 ml, P < 0.001). In a logistic linear regression analysis, only PVR urine volume was an independent predictor of de novo UI after HoLEP. The most optimal cut-off value of PVR urine volume for predicting de novo UI was defined as 39.5 ml in the receiver operating characteristics curve analysis (sensitivity, 75.0%; specificity, 74.2%; AUC, 0.815; P < 0.001).

Conclusions

About one-third of patients might undergo de novo UI following HoLEP, and most of them might have been resolved within 1-6 months. High PVR urine volume after removal of postoperative urethral catheter is associated with de novo UI after HoLEP, and could be used as a practical tool to predict postoperative de novo UI.

Funding

none

Introduction

To assess the long-term results of thulium vapoenucleation of the prostate (ThuVEP) for the treatment of symptomatic benign prostatic obstruction (BPO) retrospectively.

Methods

500 patients with symptomatic BPO were treated with ThuVEP and consecutive mechanical morcellation between January 2007 and January 2010 at our institution. Patients were reassessed 1 and 5 years after ThuVEP with International Prostate Symptom Score (IPSS), Quality of Life (QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), PSA, and prostate volume measured by transrectal ultrasound. To assess treatment effects, patients were divided into two groups according to the prostate volume: group A (<60ml) and group B (>60ml). Patient data is presented as median (interquartile range).

Results

131 patients completed the 5-year follow-up and were included in the final analysis. IPSS, QoL, Qmax, and PVR improved significantly and continued to do so during 5-year follow-up (p≤0.001). At 1-year follow-up, the median prostate volume (50 ml vs. 13 ml, p<0.001) decreased significantly with a median prostate volume reduction of 80.8% (64.3-88%). Median PSA was significantly reduced at 1-year (0.83 μl/l) and 5-year (0.72 μg/l) follow-up as compared to median preoperative PSA (3.39 μg/l) (p≤0.001). The median PSA-reduction was 77.1% (51.5-89.3%) at 5-year follow-up and significantly different between group A (70.2% (42.7-87.3)%) and group B (83.5% (70.2-91.5%)) (p≤0.006). IPSS was significantly lower at 5-year follow-up in group B compared to group A (2.5 vs. 6, p<0.001), while Qmax, QoL, PVR showed no differences at 5-year follow-up between the groups. Bladder-neck contractures (n=4) and urethral strictures (n=4) developed 3.1% of the patients each. Three patients (2.3%) were re-treated during follow-up for recurrent prostatic tissue.

Conclusions

ThuVEP is a durable procedure for the treatment of symptomatic BPO with regard to micturition improvement and prostate volume reduction. The reintervention rate of the ThuVEP procedure at long-term follow-up was low.

Funding

None.

Introduction

Objective of the study was to investigate whether the effectiveness of GreenLight XPS (GL-XPS) laser Photoselective Vaporization Prostatectomy is different in patients with or without chronic 5-Alpha-Reductase Inhibitors (5ARI) therapy._x000D_

Methods

We retrospectively evaluated prospectively collected 12 months data from the multicenter GOLIATH study regarding the 136 patients with benign prostatic hyperplasia (BPH) treated by PVP with the GL-XPS Laser System. A total of 36 patients were on chronic 5ARI therapy while 100 were not. The two groups were compared with respect to lasing density defined as kilojoules of energy applied per gram of prostate volume, prostate volume and Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement._x000D_

Results

The two groups were largely similar at baseline. Mean prostate volume was 51.7 and 47.5 g in the group taking 5ARI and the group not, respectively. Lasing time and energy used were also greater in that group (50.5±22.4 min vs 42.4±20.4 min; 269.2±138.9 kJ vs 219.2±124 kJ). Energy delivered per prostate volume was greater in the group taking 5ARIs but the difference was not statistically significant (5.5±3.1 kJ/g vs 4.8±2.3 kJ/g, p = 0.185). No statistically significant differences were observed postoperatively in the two groups regarding prostate volume reduction, PSA decrease, improvement in symptom score and uroflowmetry parameters (Table 1)._x000D_

Conclusions

Twelve-month efficacy outcomes and lasing efficiency were not statistically significantly different between the group taking 5ARI and the group not taking pharmaceuticals. 5ARI do not reduce the ability to treat patients with the GreenLight XPS laser system._x000D_

Funding

none

Introduction

Benign prostatic obstruction (BPO) is the main cause of lower urinary tract symptoms (LUTS) in men over 50 years of age. This condition is highly prevalent and many men will undergo medical or surgical treatment leading to ejaculatory dysfunction with a potential negative impact on quality of life (QoL). Through urological generations, patients were warned of the almost inevitable risk of ejaculatory dysfunction as consequence of the treatment without asking their opinion on this issue. Our objective was to evaluate with a survey the patient’s wishes on ejaculatory function after surgical treatment for BPO.

Methods

All consecutive patients with LUTS and sexually active scheduled for BPO relief surgery in a tertiary reference center were included in this prospective evaluation. All patients were offered a surgical treatment with preservation of the ejaculatory function and were informed of the risk of failure and early recurrence of LUTS with the need of medication or surgery. Once information given, patients were asked their wish about the preservation of ejaculatory function.

Results

A total of 489 patients were included with a mean age of 68.3 years [43.2 - 93.8]. Among them, 175 (36%) preferred to undergo a surgery with attempt to preserve the ejaculatory function. The mean age of this group (group 1) was 61.8 [43.2 - 81.2] compared to 71.9 [52.8 - 93.8] for the group preferring a complete BPO relief surgery (group 2), p<0.001. At the preoperative evaluation, the mean IPSS symptom score was significantly lower in group 1 compared to group 2 (18.3 [1 - 35] versus 21 [3 - 35], p=0.02). Regarding the IPSS QoL score, there was no difference between the two groups, 5.7 [0 - 6] in group 1 versus 4.45 [1 - 5] in group 2, p=0.2. No difference in Qmax was observed: 9.3 mL/s [1 - 31] in group 1 versus 7.77 mL/s [2 - 26] in group 2, p=0.45. There was also no difference in prostate volume performed with transrectal ultrasound, 57.5 mL [17 - 220] in group 1 versus 62.3 mL [15 - 164] in group 2, p=0.13. About medication, 41% were under alpha-blockers in group 1 versus 51% in group 2 (p=0.06), and 9% were under 5-ARI in group 1 versus 24% in group 2, p<0.001.

Conclusions

This survey showed that more than one third of patients with indication of surgical treatment for BPO would like to preserve antegrade ejaculation despite of the risk of failure and early recurrence of LUTS. These patients were slightly younger than the others. This issue should be taken into consideration in the decision of the urologists which may change their surgical approach to preserve this function.

Funding

None

Introduction

Guidelines for the management of very large prostates among men with symptomatic benign prostatic enlargement suggest simple prostatectomy (SP) or enucleation for those over 80g. Minimally invasive (MI) approaches to SP have been pursued to decrease procedural morbidity, with robot-assisted SP (RASP) gaining in favor. The broad effect of the advent of robotics on the frequency of SP has not been assessed. We aimed to examine trends in the use of SP in the United States in the era of growing enucleation popularity.

Methods

Using the Premier Healthcare Database, we identified men who underwent SP (ICD-9 codes 60.3, 60.4) with a concurrent diagnosis of BPH (ICD-9: 600.x), excluding those diagnosed with prostate cancer. Using a combination of ICD-9 codes and a detailed review of the billing codes, we identified procedures as as robotic (ICD-9: 17.4x), or laparoscopic (ICD-9: 54.21). We evaluated trends across the study period (2003 to 2015) in the use of SP by surgical approach (open, laparoscopic, robotic), in addition to predictors in the use of robotic and MI (laparoscopic and robotic) SP using multivariable logistic regression models. We adjusted for potential confounders and accounted for clustering by hospitals and survey weighting to ensure nationally representative estimates.

Results

A total of 43,731 SPs (40,995 open, 1,348 laparoscopic, 1,388 robotic) were performed at 414 hospitals from 2003 to 2015. Figure 1 shows the decreasing trend in number and proportion of open SP and a gradual rise in robotic SP being performed (p<0.001). Predictors of robotic SP use include lower age (OR 0.97, p<0.01), white (vs. non-white, OR 1.88, p=0.01), larger hospital bedsize (OR 3.61, p<0.01), teaching hospital status (OR 4.54,p<0.001), Northeast region (vs. Midwest, OR 5.52, p=0.01) and higher annual surgeon volume (OR 1.28, p=0.001). Predictors of MI SP include white (OR 1.53, p=0.02), higher surgeon volume (OR 1.15, p=0.08) and lower hospital volume (OR 0.93, p<0.01).

Conclusions

Though RASP is increasing as a percentage of SPs performed, it's growth in use has not lead to an increase in SP frequency, likely owing to its morbidity profile and the growing popularity of enucleation. The increasing use of MI, particularly robotic, SP is secondary to a variety of patient, hospital and surgical characteristics.

Funding

None

Introduction

Outcomes following prosthetic urethral lift implants (UroLift) (PUL) have been reported in a number of clinical trials. This investigation follows the mid term results in patients of five German centers who were treated in a normal clinical setting outside of study limitations. Previously reported studies rigorously selected subjects with mild to moderate obstruction. We report the prospective outcomes of patients treated by PUL in lieu of TURP after education concerning the less invasive therapy.

Methods

In a multicenter prospective observational study in 212 patients from five German centers were included during the period of 10/2012 through 06/2014. All candidates, submitted for transurethral resection of the prostate (TURP), received information on PUL and were given the choice of procedures. The only exclusion criterion was a prominent median lobe. No patients were excluded because of high post void residual (PVR), prostate volume (PV), history of retention, or oral LUTS therapy. Maximum urinary flow (Qmax), PVR, and the International Prostate Symptom Score (IPSS) with the Quality of Life questionnaire were assessed at baseline and 3, 6, 12, 18 and 24 months after surgery.

Results

Of the 212 candidates submitted for TURP, 85 (patient age was 38-85y) chose PUL. A total of 3.8 (2-7) implants were delivered over 57 (35-90 min) under general or local anesthesia. 38% of our more severely obstructed patients would have been denied PUL utilizing previously reported study criteria. _x000D_ 96% reported immediate symptom relief within the first month; mean Qmax, PVR, IPSS, and QoL significantly improved (p<0.001) and was maintained or further improved within the time of follow-up. Sexual function including ejaculation was unchanged or even improved of those who reported sexual activity prior to surgery. _x000D_ Eleven patients (13%) without severe obstruction but related to their high PVR underwent retreatment: two had successful additional PUL and 9 (with PVR values of 90-280ml) underwent TURP, four of which did not significantly improve further and one remained with a suprapubic catheter.

Conclusions

PUL is a new and promising surgical technique which may alleviate symptomatic BPH, even in severely obstructed patients. It is an easy surgical technique and has been efficacious in candidates who would have undergone, until now, TURP or another equivalent therapy. Within the follow-up, these patients demonstrated a similar outcome to those in published studies. _x000D_

Funding

None.

Introduction

Surgical smoke, which is produced during surgical procedures by electronic devices, contains harmful gases. Although these gases are also produced during transurethral resection (TUR), the dangers of surgical smoke in urological procedures are not widely known. The present study analyzed the gas composition of surgical smoke during TUR of the prostate (TURP), and investigated a technique to protect against the effects of harmful gases.

Methods

A total of 54 TURP (in saline) cases were enrolled and divided into two groups according to the irrigation evacuation methods: (1) spontaneous irrigation with outlets opened by natural pressure (open irrigation group) or (2) continuous irrigation with closed suction to outlets by continuous evacuation (closed irrigation group). The clinical parameters were analyzed in both groups. The conditions in the operating room during TURP were evaluated by the surgical staff with face scale questionnaires. The composition of the surgical smoke produced by TURP was collected into charcoal tubes, and analyzed by gas chromatography.

Results

The two groups did not differ in operation time or postoperative hemoglobin values, whereas resection efficiency was better in the closed irrigation group (0.45 gram/min) than in the open irrigation group (0.38 gram/min) (p=0.002). The conditions in the operating room improved significantly by a decrease in the unpleasant smell in the closed irrigation group (3.6, by face scale) compared to that in the open irrigation group (1.1, by face scale) (p<.0001). The closed irrigation system was able to expel the gases remaining in the dome of the bladder during TURP. The surgical smoke produced during TURP contained several gases including benzene and ethylbenzene, which are known carcinogens.

Conclusions

The surgical smoke produced by TURP contained carcinogenic gases. The application of the closed irrigation system during TURP would significantly improve conditions in the operating room and reduce exposure of the staff to the harmful effects of the gases by clearing this occupational hazard

Funding

none

Introduction

The introduction of three kinds of magnetic resonance imaging-guided biopsies (MRI-GB) has changed the paradigm regarding prostate biopsies. Since whether to use MRI-GB and which technique should be preferred are still matters of controversy, we aimed to compare and rank prostate biopsy strategies.

Methods

We did a network meta-analysis to incorporate both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, Scopus, Embase and the reference lists of relevant articles for randomised controlled trials published up to Sep 1, 2016, of different prostate biopsy strategies. The primary outcome was overall prostate cancer (PCa) detection rate. The secondary outcomes were clinically significant PCa (csPCa), clinically insignificant PCa (ciPCa) and positive core rate. We did pairwise meta-analyses by random effects model and network meta-analysis by Bayesian random effects model. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015026114.

Results

From a total of 3616 citations, 24 randomised trials with a total of 6 497 participants were included in this network meta-analysis. 11 prostate biopsy strategies published between 2000 and 2016 were considered. The quality of evidence was rated as low in most comparisons. Only for MRI-cognitive GB (Relative risk [RR] 2.66, 95% credible interval [CrI] 1.44-4.72) enough evidence existed to support superiority when compared with transrectal ultrasound(TRUS) (10-12)-GB. csPCa and ciPCa detection rate suggested no significant difference between any pair of groups for biopsy technique. In terms of positive core rate, MRI-cognitive was significantly effective than TRUS(10-12) (RR 4.32, 95% CrI 1.45-13.30), TPUS(10-12) (RR 4.55, 95% CrI 1.34-15.98) and TRUS(>12) PB (RR 4.80, 95% CrI 1.34-17.58). In the subgroup of patients ≥ 65 yr and PSA < 10 ng/ml, MRI/TRUS was significantly effective than TRUS(10-12) (RR 2.47, 95% CrI 1.30-4.75; RR 2.45, 95% CrI 1.20-5.09).

Conclusions

MRI-cognitive GB had better overall PCa detection rates compared with TRUS(10-12)-GB, but similar rates of csPCa and ciPCa.Nevertheless, doctors need to consider our results together with all known safety and economy information when selecting the strategy for individual patients. Head-to-head comparisons of MRI-GB techniques are limited and are needed to confirm our findings.

Funding

None

Introduction

Multiparametric MRI (mpMRI) is gaining widespread acceptance in prostate cancer (PC) diagnosis and improves significant PC (sPC) detection (Gleason-score >= 3+4). Decision making based on European Randomised study of Screening for PC (ERSPC) risk-calculator (RC) parameters may overcome PSA-screening limitations. We added pre-biopsy mpMRI to ERSPC-RC parameters and developed a risk model (RM) to predict individual sPC-risk on biopsy. _x000D_

Methods

We retrospectively analyzed clinical parameters of 755 men (biopsy-naive or after previous biopsy) who underwent mpMRI prior to MRI/TRUS-fusion-biopsy between 2012 and 2014 as training sample. The RM was validated in 404 consecutive patients in 2015. A stepwise multivariate regression analysis was used to determine significant sPC-predictors in the training set and to develop the RM. The accuracy was compared to ERSPC-RC3 (for biopsy-naive men) and 4 (for patients after previous biopsy) and PI-RADSv1.0 scoring using receiver operating characteristics (ROC). Discrimination and calibration of the RM, as well as net decision and reduction curve analyses were evaluated in validation set. _x000D_

Results

PSA, prostate volume, digital-rectal examination and PI-RADS were significant sPC-predictors and included in the RM (Figure a). ROC area under the curve (AUC) for the RM was significantly larger (0.82 each), compared to ERSPC-RC3 (0.79, p=0.004), RC4 (0.68, p<0.001) and PI-RADS (0.74-76, p=0.015 and p=0.006)(Figure b-e). Similarly, in the validation cohort, RM`s discrimination was higher for biopsy-naive and post-biopsy men (0.84 and 0.76), compared to PI-RADS (0.76 and 0.69, p=0.002 and p=0.006) and ERSPC-RC3/4 (0.79/0.74, p=0.003/p=0.146). The calibration plot demonstrated an excellent slope (1.03)(Figure f). The RM`s benefit exceeded that of ERSPC-RCs and PI-RADS in the decision which patient to biopsy and enabled the highest reduction rate of unnecessary biopsies. _x000D_

Conclusions

The novel RM, incorporating ERSPC-RC parameters and PI-RADS, performed significantly better compared to the tools alone and provides measurable benefit in making the decision to biopsy men at suspicion of PC. _x000D_

Funding

None

Introduction

To determine the effect of learning curves and changes in fusion platform during 9 years of NCI experience with multiparametric MRI (mpMRI)/TRUS fusion biopsy.

Methods

A review was performed of a prospectively maintained database of patients undergoing mpMRI followed by fusion biopsy (Fbx) and systematic biopsy (Sbx) from 2007 to 2016. The patients were stratified based on the timing of first biopsy in 3 groups. Cohort 1 included patients biopsied between 7/2007 to 12/2010, accounting for learning curve at our institution. Cohort 2 included patients biopsied from 1/2011 up to the debut of UroNav (Invivo) platform in 5/2013. Cohort 3 included patients biopsied after 5/2013. Clinically significant (CS) disease was defined as Gleason 7 (3+4) or higher. Cancer detection rates (CDR) between Sbx and Fbx during different time periods were compared using McNemar test. Age and PSA standardized CDRs were calculated for comparison between 3 cohorts.

Results

1528 patients were included in the study with 219, 549 and 761 patients included in 3 respective cohorts. Mean age, PSA and race distribution were similar across 3 cohorts. In cohort 1 there was no significant difference between CDR of CS disease by Fbx (24.7%) vs Sbx (21.5%), p=0.377. Fbx was significantly better than Sbx in detection of CS disease in cohort 2 and cohort 3 (31.5% vs 25.3%, p=0.001; 36.5% vs 30.2%, p<0.001, respectively). There was significant decline in the detection of low risk disease by Fbx when compared to Sbx in the same period (cohort 2: 14.2% vs 20.9%, p<0.001; cohort 3: 12.5% vs 19.5%, p<0.001). Age and PSA standardized CDR of CS cancer by Fbx increased significantly between each successive cohort (cohort 1 and 2: 5.2%, 95% CI [2.1-8.5]), 2 and 3 (5.2%, 95% CI [1.8-8.6]). While CS CDR in patients with a prior negative biopsy was not significantly different between Fbx and Sbx in cohort 1, it was significantly different in cohorts 2 and 3 (p=0.388, p>0.001, p=0.036, respectively).

Conclusions

Our results show that after an early learning period using Fbx, CS prostate cancer was detected at significantly higher rates with Fbx than with Sbx, and low risk disease was detected at lower rates. Advances in software allowed for even greater detection of CS disease in the last cohort. This study shows that accuracy of Fbx is dependent on multiple factors; surgeon/radiologist experience and software improvements together produce improved accuracy.

Funding

This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org.

Introduction

Although prostate biopsies targeted only to MRI detected lesions allow for the detection of clinically significant diseases, they would not result into a complete sampling of the entire prostate. Therefore, lower grade tumors (i.e., non-index lesions) in other areas would not be detected. We hypothesized that the presence of non-index lesions might impact on the risk of adverse outcomes at radical prostatectomy (RP)

Methods

761 PCa patients treated with RP between 2012 and 2016 were identified. All biopsy specimens were re-reviewed by two high-volume dedicated uro-pathologists. The index lesion was defined as the highest-grade core at biopsy. When multiple positive cores were present, the index lesion was defined as higher-grade disease or higher number of positive cores with higher-grade disease from the same location. Non-index lesions were defined as lower grade or lower number of positive cores in other areas. Multivariable logistic regression (MVA) analyses tested the impact of the non-index lesions and of the number of positive non-index lesion cores on the risk of extracapsular extension (ECE), seminal vesicle involvement (SVI), and positive surgical margins (PSM). AUC of the models without information on the presence of non-index lesions were compared with full models using the DeLong method.

Results

Overall, 284 (37.5%), 83 (10.9%), and 145 (19.1%) patients had ECE, SVI, and PSM at final pathology. At MVA, the presence of non-index lesions was a predictor of ECE (Odds ratio [OR]: 2.12; P=0.001), SVI (OR: 2.75; P=0.02), and PSM (OR: 2.16; P=0.01). Similarly, the number of positive cores in the non-index lesion was associated with the risk of ECE (OR: 1.09; P=0.02), SVI (OR: 1.13; P<0.001), and PSM (OR: 1.07; P=0.01). The inclusion of information on non-index lesions improved the accuracy of the model predicting PSM (AUC: 67.0 vs. 69.4%; P=0.04). No differences in the AUCs of the base model and of the model including the presence of non-index lesions were observed for ECE (78.8 vs. 78.6%; P=0.7) and SVI (81.5 vs. 82.1%; P=0.3).

Conclusions

The presence of non-index lesions and the number of positive cores in the non-index lesion represent predictors of ECE, SVI, and PSM. The inclusion of these parameters improves our ability to identify patients at higher risk of PSM. A systematic sample of the prostate provides useful preoperative information on the risk of adverse pathologic outcomes and should be always considered in association with targeted biopsies.

Funding

none

Introduction

The aim of this study was to compare the detection rate of clinically significant prostate cancer (csPCa) of different mpMRI targeted approaches and to assess the role of operator expertise on the detection of csPCa

Methods

244 patients underwent mpMRI targeted biopsy (cognitive-CB or fusion-FB) between 2013 and 2016 at a single tertiary referral centre. A 1.5 T mpMRI study using an endorectal coil was performed in all men. All procedures were performed by four operators. csPCa was defined as Gleason Score at biopsy ≥7. Operator expertise was coded as progressive number of targeted biopsies performed by each physician. Multivariable logistic regression analyses (MVA) were used to assess the association between type of targeted biopsy technique (FB vs. CB) and operator expertise (modelled by natural log function) with the detection of csPCa. Covariates consisted of PSA, prostate volume, PIRADS v.2 (3 vs. >3), number of targeted cores per MRI lesion, digital rectal examination (negative vs. positive). The same analyses were performed only in patients undergoing FB, after accounting also for type of FB approach (trans-rectal vs. trans-perineal). Lowess smoother weighted function was used to graphical assess the effect of operator expertise on the probability to detect csPCa in FB group, after accounting for all confounders

Results

Overall, 157 (64.3%) patients underwent FB and 87 (35.7%) underwent CB. Overall csPCa detection rate was 57.9 vs. 44.8% for FB and CB, respectively (p=0.07). A significantly higher csPCa detection rate of targeted samples alone was also observed for FB as compared to CB (56.7 vs. 35.6%; p=0.002). At MVA, FB and operator expertise were significantly associated with higher probability of csPCa detection in targeted samples (OR: 2.4 and 1.7, respectively; all p≤0.03). When the same analyses were repeated in those patients undergoing FB, operator expertise remained an independent predictor of csPCa (OR: 1.9; p=0.004). A progressive increase of the probability to detect csPCa with the increasing number of performed procedures was observed (Fig. 1)

Conclusions

We provided evidence that FB had higher detection rate of csPCa relative to CB. Moreover, operator expertise was significantly related to the detection of csPCa

Funding

none

Introduction

The fusion of multiparametric (Mp) magnetic resonance imaging (MRI) with real time 3D ultrasound during prostate biopsy is gaining popularity. The aim of this study was to evaluate the diagnostic performance of Mp-MRI using a per-core analysis of patients who underwent prostate “fusion” biopsy

Methods

Baseline, clinical and pathological data of 498 consecutive patients who underwent Mp-MRI/ultrasound “fusion” biopsy of prostate were prospectively collected in three centres between October 2013 and October 2016. The UroStation™ (Koelis, France) and ultrasound system with an end-fire 3D TRUS transducer were used for the imaging fusion process. _x000D_ Diagnostic accuracy of Mp-MRI was evaluated in the whole cohort and in those patients with Gleason score >6, separately. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Ac) of Mp-MRI were assessed on the base of a per core analysis of histologic findings._x000D_

Results

Demographic data are reported into Table 1._x000D_ Out of 498 patients, 286 had a PCa diagnosis (57.4%); 162 of them (32.5%) were Gleason score ?7. Overall, 9360 cores were taken: Se, Sp, PPV, NPV and Ac of Mp-MRI in the whole cohort were 46.5%, 81.7%, 36.6%, 87% and 75.2%, respectively. When restricting the analysis to Gleason scores >6, Se, Sp, PPV, NPV and Ac were 45.9%, 79.8%, 25.1%, 90.9% and 75.4%, respectively. In a per patient analysis, the detection rate of PI-RADS scores 3,4 and 5 were 24%, 68% and 93.6%, respectively, while for Gleason score PCa>6 the detection rate of PIRADS 3, 4 and 5 were 6%, 35.2% and 73.4%, respectively.(Table 1). In a per core analysis, the PPV of PI-RADS scores 3,4 and 5 were 8.5%, 37.8% and 73.2%, respectively, while the PPV of PI-RADS scores for Gleason score PCa>6 were 5.1%, 21.2% and 62.2%, respectively. (Table 2)_x000D_

Conclusions

This study confirmed high PCa detection rates with Mp-MRI-ultrasound fusion biopsy. A meticulous analysis of 9360 biopsy cores taken showed a poor sensitivity and PPV of Mp-MRI, especially for Gleason score >6 PCa. Despite the poor discrimination of PI-RADS scores of 3 and 4, PIRADS scores 5 correctly identified PCa lesions with Gleason scores >6.

Funding

none

Introduction

Multiparametric MRI (mpMRI) improves the detection of significant prostate cancer (PC) and extraprostatic extension (EPE). We combined pre-biopsy mpMRI data and clinical parameters to develop a risk model (RM) to predict individual side-specific risk of EPE on radical prostatectomy (RP).

Methods

MRI and clinical parameters of 132 men who underwent mpMRI fusion-biopsy and RP were analysed as training set. The RM was validated prospectively in 132 consecutive patients. Multivariate regression analysis was used to determine EPE predictors for RM development. The calibration of the RM was analysed using a calibration plot. The accuracy was compared to digital rectal examination (DRE), ESUR MRI criteria for EPE alone and the nomogram for side-specific EPE prediction of Steuber et al., using receiver operating characteristics (ROC) in training and validation set. Differences between the ROC curves were analysed using Likelihood ratio tests.

Results

Primary Gleason pattern on biopsy on specific side, ESUR MRI criteria of side-specific lesion, PSA-density, clinical T-stage, lesion volume in milliliter and capsule contact length in millimeter on MRI were significant EPE-predictors and were included in the RM (Figure a). The calibration plot of the RM showed that predicted and actual probabilities were close (slope 1.12)(Figure b). ROC area under the curve (AUC) for the RM was significantly larger in both sets (0.88 and 0.84), compared to DRE (0.69, p=0.004, 0.66, p<0.001) and the risk model of Steuber et al. (0.77, p=0.009, 0.71, p=0.006). Compared to ESUR criteria (AUC 0.87 and 0.80), the AUC was only significant larger in the validation set (p=0.03) (Figure c/d).

Conclusions

The RM, incorporating clinical and standardized MRI parameters performed significantly better compared to a renowned risk model, ESUR MRI criteria and clinical parameters alone. Thus, it provides accurate individual risk stratification of side-specific EPE of prostate cancers prior to RP.

Funding

None

Introduction

Dynamic contrast-enhanced imaging (DCE) is recommended by Prostate Imaging - Reporting And Data System (PI-RADS) guidelines in addition to the combination of T2-weighted imaging (T2W) and diffusion-weighted imaging (DWI) for prostate cancer (PCa) detection, but its usefulness is not well-established. We compared the performance of biparametric (T2W+DWI) and triparametric (T2W+DWI+DCE) MRI, in the diagnosis of the index lesion.

Methods

Fifty-seven patients (who underwent preoperative mpMRI and radical prostatectomy) and 23 controls (examined by mpMRI, with at least a 2-year follow-up excluding PCa) were retrospectively analysed. Biparametric MRI and triparametric MRI (the latter according to PI-RADSv2) were reviewed by 5 independent radiology residents, allowing a 4-week interval between the two sessions. Each reader had an 8 months dedicated MRI experience and was blinded to clinical and pathological data. A senior consultant uro-pathologist reviewed whole-mount sections (according to 2014 ISUP protocol), providing the reference standard for comparing diagnostic accuracy. The index lesion was defined as the largest PCa focus identified at the final pathology.

Results

No statistically significant difference in index lesion detection was observed among bi- and triparametric MRI, in a pooled analysis of the 5 readers. Sensitivity was 72% and 81% respectively (p=0.08); specificity was 78% and 79% (p=0.92); accuracy was 74% and 81% (p=0.12; Figure 1). The larger lesion had also the higher Gleason score in 53/57 patients (92,9%). Bi- triparametric MRI did not differ significantly in measuring lesion diameter (p=0.54), although histologic value was significantly higher than measures of both imaging protocols (+54% on average, p=0.01).

Conclusions

No significant difference in detecting and measuring prostate cancer index lesion was observed by adding DCE sequences to T2W and DWI, among MRI readers with intermediate experience. The sole use of biparametric prostate MRI can provide a good diagnostic accuracy on index lesions.

Funding

None

Introduction

Identifying clinically significant prostate cancers is the main objective of prostate cancer diagnosis. The aim of this study was to develop, to internally validate and to calibrate a nomogram to predict the probability of detecting a clinically significant prostate cancer.

Methods

Prospectively collected data from 3 tertiary referral center series of 478 consecutive patients who underwent MRI-US fusion biopsy using the UroStation (Koelis, France) were used to build the nomogram. A logistic regression model is created to identify predictors of PCa diagnosis with MRI-US fusion biopsy. Predictive accuracy was quantified using the concordance index (CI). Internal validation with 200 bootstrap resampling and calibration plot were performed.

Results

Mean age was 66.3 yrs (± 7.98) and mean PSA levels were 9.8 ng/mL (± 7.98). The overall PCa detection rate was 57.4%. _x000D_ Age, PSA serum levels, PIRADS score at MRI report, number of targeted and number of systematic cores taken were included in the model (Figure 1). Predictive accuracy was 0.81. On internal validation the CI was 0.81 and predicted probability was well calibrated (Figure 2). _x000D_ Limitations include the lack of external validation and the absence of patients with races different by Caucasian in the development cohort._x000D_

Conclusions

Predicting the risk of a clinically significant PCa is the goal of physicians. This nomogram provides a high accuracy in predicting the probability of diagnosing a clinically significant PCa with MRI-US fusion biopsy. The ease to use makes this nomogram a clinical tool for both patients and physicians.

Funding

none

Introduction

In the setting of active surveillance and focal therapy for prostate cancer (PCa), precise localization of the index lesion is crucial to ensure good oncological outcomes. Our objective was to assess the accuracy of multiparametric MRI (mp-MRI) for index lesion localization. _x000D_

Methods

We conducted a retrospective bi-centric study including 405 patients operated by radical prostatectomy from 2010 to 2015 and having been assessed preoperatively by mp-MRI in two national referral centres for PCa management._x000D_ Pre-operative mp-MRI sequences included T2-weighted, diffusion weighted, and dynamic contrast enhanced and were acquired from 1,5 (n=344) or 3 Tesla (n=61) with external phased array coils. The MRI index lesion was defined as the lesion with the highest PI-RADS score. The pathological index lesion was defined as the lesion with the greatest Gleason score. If there were multiple lesions with the same PI-RADS or Gleason score, the largest one was considered as the index lesion. A neighbouring method, dividing the prostate in 12 sectors, was applied to determine the concordance between mp-MRI findings and pathology reports for index lesion localization.

Results

Out of the 405 patients, 385 (95%) had an index lesion identified on the mp-MRI and 20 (5%) had a normal mp-MRI. On pathology reports, the Gleason score was 6 in 113 (28%), 7 in 252 (62%) and ≥ 8 in 40 (10%) of the patients. The index lesion diameter was greater than 10mm in 336 (83%) patients. For index lesion detection, mp-MRI had a sensitivity of 63%, a specificity of 67% and a positive predictive value of 66%. Increased sensitivity was obtained for larger tumors on mp-MRI (>10mm, 194/275; 71%) and greater biopsy Gleason score tumors (≥7, 147/202; 73%). _x000D_ In multivariate analysis, the detection of the index lesion by mp-MRI was significantly improved when the biopsy Gleason score was ≥ 7 (4+3) (p=0.001), the index lesion mp-MRI size was > 10mm (p<0.001) and the prostate weight was ≤ 50g (p=0.017).

Conclusions

In this contemporary assessment, mp-MRI failed to localize the index lesion in up to 40% of cases. Larger tumor sizes on mp-MRI and higher Gleason scores on biopsy cores were associated with significantly higher sensitivity of mp-MRI for index lesion localization.

Funding

none

Introduction

MR/US fusion biopsy (FB) is a promising modality for detection of clinically significant prostate cancer (csPCa), defined as Gleason >=7 in patients who have had a prior negative biopsy. The purpose of this study is to assess the learning curve with adoption of FB using PI-RADS Version 2 (v2) for detecting csPCa and to identify patient and technical factors that predict success.

Methods

A total of 113 consecutive patients with at least one prior negative biopsy and a multiparametric MRI (mpMRI) exam of the prostate with a PIRADS 3 or greater index lesion underwent FB at a single academic center previously naive to FB technology. Outcomes are detection rates for Gleason 6 cancer, csPCa, and any cancer. The following 22 covariates were analyzed: age, body mass index (BMI), PSA, prostate volume (MRI-estimated), prostate volume (US-estimated), PSAD (MRI-estimated), PSAD (US-estimated), time interval since the last negative SB, number of prior negative systematic biopsies, number of targeted biopsy cores of the index lesion, size of index lesion, PI-RADS v2 score, number of suspicious lesions on mpMRI, institution experience, surgeon, obesity, digital rectal exam (DRE), atypical small acinar proliferation (ASAP) on prior biopsy, high-grade prostatic intraepithelial neoplasia (HGPIN) on prior biopsy, and location of index lesion (zone, region, and sector). Multiple logistic regression with model selection was used to select covariates having significant effects on the outcome._x000D_

Results

Prostate cancers were identified in 52% of cases. Among patients diagnosed with prostate cancer, 80% were clinically significant. The detection rates of csPCa using FB when a PIRADS 3, 4, or 5 index lesion was present on mpMRI were 6%, 46%, and 66%, respectively. PI-RADS v2 score had a predictive accuracy (AUC) of 0.79 for csPCa detection. Institutional experience over time, MRI-estimated prostate volume, and PI-RADS v2 score were independent predictors of success at detecting csPCa.

Conclusions

Since FB is a highly technical and experience-driven process, development of internal quality measures to assess the institutional learning curve and the quality of PI-RADS v2 scoring is critical with adoption of this technology.

Funding

none

Introduction

To evaluate mpMRI-based assessments of neurovascular bundle (NVB) infiltration and to determine the value of PI-RADS V2 scores for the prediction of NVB-infiltration before prostatectomy.

Methods

Our institutional review board approved the study. 198 patients underwent standardized mpMRI at 3T prior to surgery, including high resolution T2w-TSE-imaging in 3 planes, T1-w-TSE, DWI with ADC map, PD-TSE and Gd-DCE with post-processing of images. Assessment for NVB-infiltration was made for each side of each prostate (n=396). Maximum PI-RADS-V2 scores were determined for the posterolateral areas adjacent to the NVB (n=396). MRI-findings were correlated to pathologic analysis as reference standard, where NVB-infiltration was defined as tumor invasion into the NVB or extraprostatic expansion (EPE) in the posterolateral area adjacent to the NVB.

Results

Overall T-staging accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI were 78.3%, 644 %, 892 %, 82.4% and 76.2%, respectively. In 396 cases infiltration of the NVB was predicted with 89.4%, 75.2%, 94.0%, 80.2% and 92.1% overall accuracy, sensitivity, specificity, PPV and NPV, respectively. By correlating 365 maximum PIRADS-V2 scores to the pathology of adjacent NVBs, infiltration was demonstrated in 13 NVBs despite low likelihood of cancer presence (PI-RADS 1 or 2 scores), amounting to 14% false negative predictions.

Conclusions

mpMRI-based assessment of NVB-infiltration should be acknowledged when nerve sparing surgery is considered. However, areas without tumor suspicion (PI-RADS 1 or 2) might demonstrate NVB-infiltration in pathology causing false negative predictions.

Funding

none

Introduction

There is growing interest on the using of prostate mpMRI for performing targeted biopsies. However, lack of consensus exists whether it is mandatory to perform concomitant systematic biopsies. The aim of this study was to assess the predictors of clinical significant prostate cancer (csPCa) outside the mpMRI detected index lesion (IL) and to assess whether MRI parameters may predict csPCa outside IL

Methods

244 patients underwent mpMRI of the prostate with subsequent biopsy between 2013 and 2016 at a single tertiary referral centre. A 1.5 T mpMRI study using an endorectal coil was performed in all patients. Lesions suggesting of significant PCa visualized on mpMRI, defined as PI-RADS v.2 ≥3, were targeted with cognitive or fusion approach. Furthermore each patient was submitted to standard random biopsy during the same session. csPCa was defined as Gleason Score ≥7. Multivariable logistic regression analysis (MVA) was performed to assess the predictors of csPCa outside the IL. Covariates consisted of age at biopsy, PSA, prostate volume, digital rectal examination (negative vs. positive), PI-RADS (3 vs. >3), IL volume, number of ILs, number of random cores and previous biopsy (biopsy naive vs. previous negative biopsy vs. previous positive biopsy)

Results

Overall, 46 and 54% of patients were previous biopsied and biopsy naive, respectively. Median PSA, prostate volume, number of random cores, number of ILs, IL volume were 7 ng/ml, 47 cc, 12, 1, 0.70 cc, respectively. The overall detection rate of csPCa outside the IL was 34%. When patients were stratified according to the targeted biopsy results, the detection rate of csPCa outside the IL was 10 and 30% in men with a negative and positive targeted biopsy, respectively. At MVA age (OR: 1.07; p=0.01), PSA (OR: 1.12; p=0.01), prostate volume (OR: 0.98; p=0.02), positive digital rectal examination (OR 3.7; p<0.01) and previous negative biopsy (OR 0.31; p=0.01) were independent predictors of the presence of overall csPCa outside the IL (AUC: 65%). Conversely, PI-RADS, IL volume, number of ILs detected at mpMRI were not associated with overall detection of csPCa outside the IL (all p≥0.1)

Conclusions

mpMRI missed csPCa outside the IL in approximately a third of men. Despite the presence of clinical predictors, neither patient characteristics nor mpMRI data are able to reliably select patients candidate for targeted biopsy alone (AUC: 65%). Therefore, based on our data, systematic biopsies should be always performed in conjunction with targeted biopsy in men with suspected csPCa at mpMRI

Funding

none

Introduction

Focal therapy of prostate cancer might be an alternative to radical prostatectomy (RP) in treating patients with low- or intermediate-risk disease. Since MRI alone might not be sufficient in tumor location, template perineal biopsy is performed. To investigate the accuracy of locating a tumor focus we compared the results of multiparametric (mp)MRI and perineal stereotactic MRI-based TRUS-guided fusion biopsy (SFB) with the histopathology of the radical prostatectomy specimen.

Methods

All patients who underwent a SFB in our hospital with positive findings of tumor that lead to a RP from 08/2012 to 07/2016 were included. MRI of the prostate was performed multiparametric and evaluated according to PI-RADS-classification. Lesions were marked 3-dimensionally by the radiologist. The SFB was performed using the BiopSee ©-platform. Lesion-targeted and random biopsies were taken. The cores’ positions in the prostate were recorded. Cores were embedded separately, the basal tips got marked with dye. In the histopathological report the location of tumor in the core in terms of apical, mid or base location was mentioned. Thereby tumor-foci location could be projected on the prostate in 3 dimensions. In the prostatectomy-specimen (whole mount step section) the tumor’s location was reported by the pathologist. A single investigator determined the conformity of all three results visually: good (all 3 results matching), intermediate (MRI or biopsy matching with prostatectomy’s result), and poor conformity (no match at all).

Results

128 patients could be included. 103 patients (79.8 %) showed good, 17 (13.2 %) intermediate, and 8 (6.2 %) poor conformity of the tumor’s location. According to oncological criteria (PSA< 15 ng/ml, Gleason max. 7a, cT1-2a, unilateral disease) 67 patients (52%) would have been suitable for focal therapy. From these 50 (75%)would have been in good conformity, 12 (18%)in intermediate and 5(7,%) in poor conformity to the prostatectomy result.

Conclusions

These results show a high accuracy in locating the tumor by SFB. This could give a good base for a precise focal therapy that is not only sufficient in terms of treating all tumor cells but also in sparing surrounding structures by avoiding over-estimation of the extensions of he foci.

Funding

None

Introduction

To evaluate the cancer detection rate in negative multiparametric magnetic resonance imaging (mp-MRI) patients who accept the first time prostate biopsy. To analyze the potential influential factors of prostate cancer diagnosis.

Methods

The records of men undergoing prostate biopsy were retrospectively collected between July 2011 and June 2016. The PI-RADS score was used to evaluate the prostate imaging according to the European Society of Urological Radiology (ESUR) guideline and PI-RADS 1~2 was defined as negative. Finally, 196 patients were MRI negative. All the patients accepted T1, T2 and DWI image. Part of them had DCE image.The mean diagnosis age is 66.6±9.0yrs, and the median PSA is 7.44ng/ml.All patients accepted the transrectal ultrasound guided systematic 12-coreprostate biopsy._x000D_ Statistical analysis was carried out with the SPSS 19.0 computer package. A P value<0.05 was considered statistically significant._x000D_

Results

There were 196 patients enrolled, with the mean diagnosis age 66.6±9.0yrs, and the median PSA 7.44ng/ml. Of the 196 patients, there were 42(21.4%) diagnosed with prostate cancer, of which, 30 were clinically significant.The negative predictive value (NPV) was 78.6% for prostate cancer, and 84.7% for clinically significant prostate cancer.(a_image, b_image)_x000D_ Age and serum PSA were related with positive diagnosis. Patients over 70yrs was associated with a 2.4-fold higher risk for prostate cancer, which was 1.47 when patients were divided according to the PSA level of ≤4ng/ml, 4~10ng/ml, 10~20ng/ml and >20ng/ml.(c_image)

Conclusions

Clinical significant prostate cancer may exist in negative MRI patients in first time biopsy. The age and PSA level relate to the cancer detection rate.

Funding

none

Introduction

Prostate cancer (PCa) remains the only solid organ tumor that is diagnosed by a non-targeted sampling method. Recently, multi-parametric MRI (MP-MRI) in conjunction with an MRI- ultrasound (US) fusion guided biopsy (bx) has demonstrated improved PCa detection. Unfortunately, this technology has been limited to tertiary care centers. Therefore, we sought to compare cognitive versus targeted software to assess the ability of cognitive registration to disseminate more readily into the community.

Methods

Consecutive patients underwent an MRI-US fusion prostate bx for elevated PSA, abnormal DRE, active surveillance or prior negative bx with a persistently elevated PSA. All subjects underwent pre-bx MP-MRI and lesions visible on MRI were graded using the PI-RADS version 2 classification system. The UroNav bx tracking system was used to fuse the stored MR images with real-time US generating a 3D model, which was then used to sequentially perform cognitive, targeted, and standard 12 core systematic biopsies in an office setting under local anesthesia. Descriptive statistics included patient characteristics and univariate analysis was done using logistic regression analysis to detect the associations between presence of cancer, clinically significant cancer, demographic variables, and bx method. Signed rank test was used for paired comparisons amongst bx method.

Results

44 patients (median age 66 yrs, median PSA 6.4) underwent an MRI-US fusion bx between July 2014 and October 2015 with an overall CDR of 59%. Cognitive CDR was 40.9% with 25% being clinical significant disease. The targeted CDR was 27.3% with 22.7% being clinically significant disease. Overall, the cognitive approach had a sensitivity of 69.2% (95% CI: 50%, 88%) whereas the targeted approach had sensitivity of 46.2% (95% CI: 26%, 67%). Furthermore, the targeted approach missed 8 cancers when compared to the cognitive approach, whereas, the cognitive approach missed 2 cancer when compared to the targeted approach. The difference in sensitivity is most pronounced when comparing standard and targeted methods (p=0.02) and approaches significance when comparing cognitive and targeted methods (p=0.11).

Conclusions

MRI-US fusion targeted software when compared to the cognitive platform, was not found to have higher cancer detection rate nor sensitivity. We believe this highlights the importance of the MRI itself, rather than the platform used.

Funding

None

Introduction

The wide diffusion of multiparametric magnetic resonance imaging (MRI) has dramatically modified the scenario of prostate cancer (PCa) diagnosis. The detection rate of MRI-ultrasound (US) fusion biopsy increased as well as the need for an extended prostate biopsy sampling with saturation biopsy decreased. The aim of this study was to develop, internally validate and calibrate a nomogram to predict the probability of detecting a prostate cancer.

Methods

Prospectively collected data from 3 tertiary referral center series of 475 consecutive patients who underwent MRI-US fusion biopsy using the Koelis system were used to build the nomogram. A logistic regression model is created to identify predictors of PCa diagnosis with MRI-US fusion biopsy. Predictive accuracy was quantified using the concordance index (CI). Internal validation with 200 bootstrap resampling and calibration plot were performed.

Results

Mean age was 66.3 yrs (±7.98) and mean PSA levels were 9.8 ng/mL(±7.98). The overall PCa detection rate was 57.4%._x000D_ Age, PSA serum levels, PIRADS score at MRI report, number of targeted and number of systematic cores taken were included in the model (Figure 1).Predictive accuracy was 0.82. On internal validation the CI was 0.81 and predicted probability was well calibrated (Figure 2)._x000D_ Limitations include the lack of external validation and the absence of patients with races different by Caucasian in the development cohort._x000D_

Conclusions

This nomogram provides a high accuracy in predicting the probability of PCa diagnosis with MRI-US fusion biopsy. This is an easy to use clinical tool that physicians may use for patients counselling purposes.

Funding

none

Introduction

To evaluate the impact of urologist learning curve (LC) for mpMRI-TRUS fusion biopsy on clinically significant PCa (sPCa) detection rate. _x000D_

Methods

Data from 291 patients who underwent mpMRI-TRUS transperineal/transrectal targeted (TB) and systematic transrectal biopsy (SB) for suspicion of PCa were prospectly collected at a single institution. For mpMRI-TRUS fusion-guided prostate biopsy, the BioJet fusion system (D&K Technologies, Germany) was used; biopsies were performed in a transrectal or transperineal setting according to the location of the primary lesion on the mpMRI. All the procedures were performed by two urologists who had already experience with TRUS guided random prostate biopsies. mpMRI studies were reported by different experienced radiologists. The cohort was divided into six groups representing consecutive times during the study period. Overall PCa detection rate (CDR) and csPCa detection rate (csCDR), defined with Epstein criteria, were reported and stratified according to progression groups. Sensitivity, specificity, negative predictive value and accuracy of MRI-TRUS TB were calculated. Linear regression analyses were performed to evaluate the learning curve of the procedure.

Results

Overall PCa detection rate was 42.6% (n=124) and csPCa detection rate was 28% (n=81). CDR at target biopsy was 38% (n=111). Considering CDR stratified according to PIRADS, we reported 16.7% (n=1), 21% (n=22), 50.7% (n=74) and 75% (n=27) for PIRADS 2, 3, 4 and 5 respectively(p<0.01)._x000D_ Cancer detection rate increased from 38.8% to 42.6% from group A to group F (R2=0.06). csCDR and target biopsy CDR increased from 22% to 42% (R2=0.002) and from 38.8% to 39.5% (R2=0.7) respectively. Sensitivity, specificity, NPV and accuracy of TB in detecting PCa was 79% (CI: 0.68-0.89), 73% (CI: 0.66-0.78), 93 % (0.89-0.96) and 74% (0.68-0.79) respectively. Sensitivity, specificity, NPV and overall accuracy of TB in detecting csPCa was 93% (CI: 0.86-0.98), 83% (CI :0.77-0.87), 96% (CI:0.94-0.99) and 85% (CI: 0.81-0.89) respectively. When the LC impact was assessed, overall diagnostic accuracy on PCa and csPCa of TB did not show a significant increasing trend (R2=0.5 and R2=0.09).

Conclusions

We failed to demonstrate a statistically significant impact of LC for PCa and csPCa detection. mpMRI-TRUS-TB seems to be an easy, reliable and feasible procedure in the hands of experienced urologists. Our findings represent a starting point for faster widespread of the technique in the urological practice.

Funding

none

Introduction

The aim of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) scoring system for prostate cancer detection in the peripheral zone (PZ) and the transition zone (TZ) using MRI/trans-rectal ultrasonography (US) fusion targeted biopsy as a reference standard.

Methods

We retrospectively reviewed 762 patients who underwent 3-Tesla multi-parametric (mp)-MRI and the following MRI/US fusion targeted biopsy, all of which were performed by experienced urologists (10/2012-8/2015). We excluded patients in whom MRI did not identify any suspicious lesions and radiologists who reported in less than 50 cases. Finally, 648 patients with 1255 suspicious lesions were included in this study. The mp-MRIs were reported on a 5-point Likert scale of suspicion. The UroStation^® (Koelis, France) was used for the image fusion. Clinically significant cancer was defined as biopsy Gleason score ≥7.

Results

Median age was 64 years, pre-biopsy prostate-specific antigen (PSA) level was 6.93 ng/ml and estimated prostate volume was 52.1 ml. _x000D_ Of 1255 suspicious lesions on MRI, 62.4% (n=783) were located in the PZ and 19.5% (n=245) in the TZ. _x000D_ There was no significant difference in the proportion of 5-point suspicious grades between the PZ and the TZ (p=0.077)._x000D_ In comparison between the PZ and the TZ, there was no significant difference in overall cancer detection rate in grade 1-2 lesions (11.8% vs 15.1%, p=0.362), grade 3 lesions (26.9% vs 19.8%, p=0.163) and grade 4-5 lesions (55.4% vs 50.0%, p=0.551)._x000D_ Regarding clinically significant cancer detection rate, there was no significant difference in grade 1-2 lesions between the PZ and the TZ (3.1% vs 6.6%, p=0.087). In contrast, statistical differences were noted in grade 3 lesions (15.1% vs 5.9%, p=0.019) and grade 4-5 lesions (45.9% vs 23.7%, p=0.013) between the PZ and the TZ. _x000D_

Conclusions

The diagnostic reliability of mp-MRI for detecting clinically significant cancer in the TZ was less than that in the PZ. Although grade 3 lesions in the TZ showed similar overall cancer detection rate compared to that in the PZ, clinically significant cancer detection rate of grade 3 lesions in the TZ was quite lower than that in the PZ. Improvement of radiologist's interpretation, grading system itself, or targeting technique for grade 3 lesions in the TZ should be re-considered.

Funding

none

Introduction

Apparent diffusion coefficient (ADC) grade is increasingly reported in prostate magnetic resonance imaging (MRI). We evaluated the usefulness and limitations of ADC grade for peripheral zone (PZ) and transitional zone (TZ).

Methods

We reviewed the data of 455 consecutive men who underwent 3.0 Tesla diffusion-weighted MRI before radical prostatectomy from January 2015 to May 2016. The level of suspicion from the ADC map was graded using the 5-grade Likert scale. Patients with a Likert grade ≥ 3 were included in the final analysis. The MRI index lesion was defined as the lesion with highest grade or the largest lesion when multiple lesions had an identical grade. After radical prostatectomy, topographic analyses were performed on the intraprostatic location of tumor foci at each specimen. The pathologic index tumor was defined as the tumor with the highest Gleason score or largest tumor when multiple foci had an identical GS. We matched the location between MRI index lesions and pathologic index tumors. The concordance rate was compared between the PZ and TZ using chi-square tests.

Results

In 455 patients with prostate cancer, 350 (77%) had suspicious MRI index lesions (ADC grade ≥ 3). Of the 350 lesions, 58% were seen in the PZ and 42% in the TZ. The overall concordance rate was gradually increased from ADC grade 3 to 5 (52%, 72%, and 86%) and biopsy Gleason score 6 to ≥ 8 (68%, 77%, and 80%). The overall concordance rate in the PZ was significantly higher than in the TZ (82% vs. 67% p < 0.01). The concordance rate in the PZ was higher than in the TZ among the subgroup of patients with ADC grade 5 (91% vs. 76%, p = 0.007). However, the rate was similar among the subgroup of patients with ADC grade 3 (50% vs. 54%, p = 0.78).

Conclusions

ADC grade from diffusion-weighted MRI is more useful in men with PZ tumor than in those with TZ tumor. Especially, ADC grade 5 in the PZ showed higher accuracy for the detection of index tumor.

Funding

None

Introduction

Bladder cancer is the sixth most common cancer in the United States, but the most expensive from diagnosis to death. Costly surveillance and treatment can lead to financial toxicity (FT), an adverse financial condition as a consequence of the treatment of a disease. The purpose of this study is to define the prevalence of FT among patients with bladder cancer and identify causes for delay in care.

Methods

Bladder cancer patients were identified from the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC), which includes patient-reported data on FT. FT was defined at agreement with the following statement “you have to pay more for medical care than you can afford.� Demographic characteristics and factors leading to delayed care were compared using Fisher’s exact tests.

Results

144 bladder cancer patients were enrolled in HR/CSC, of which 138 completed the baseline questionnaire. Median age was 66.9 years. 75% were male, 89% were white, and 66% had less than a college degree. Half of patients had a stage of cT2 or higher. Thirty-three participants overall (24%) endorsed FT. Participants with FT were more likely to be younger, black, and have less than a college degree (p<0.01). Patients with non-invasive disease were more likely to report FT than those with invasive bladder cancer (15% vs. 30%; p=0.04). Patients who endorsed FT were more likely to report delaying care (19.8% vs. 35.1%) although this did not reach statistical significance (p=0.07). Patients reporting FT were more likely to delay care due to inability to take time off work (p=0.04) and inability to afford general expenses (p=0.04).

Conclusions

FT is a major concern among bladder cancer patients, with nearly 25% reporting that healthcare costs are more than they could afford. Younger patients were more likely to experience FT, which may be related to Medicare eligibility at age 65, which increases affordability of care. Higher rates of FT among non-invasive disease may reflect long-term, costly surveillance.

Funding

none

Introduction

Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario.

Methods

We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality.

Results

Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Figure). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE.

Conclusions

Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE.

Funding

Ajmera Family Chair in Urologic Oncology

Introduction

The effect of non-muscle invasive bladder cancer (NMIBC) on health-related quality of life (HRQOL) is poorly understood. We evaluated changes in HRQOL in patients with a new diagnosis of NMIBC compared with the general population using the Surveillance Epidemiology and End Results (SEER) Medicare Health Outcomes Survey (MHOS) database.

Methods

We identified 325 Medicare beneficiaries diagnosed with NMIBC between initial and 2-year follow-up using SEER-MHOS data (1998-2013). NMIBC patients who underwent cystoscopy with biopsy or transurethral resection of bladder tumor(s) for bladder cancer were propensity matched 1:5 to non-cancer controls (n=1685). Changes from baseline in the physical component score (PCS) and mental component score (MCS), which are normalized to between 0-100, where 50 represents the US population mean, were compared between NMIBC patients and non-cancer controls with χ² testing and multivariate linear regression analysis. We secondarily assessed differences in urinary symptoms on post-diagnosis surveys with univariate and multivariate models.

Results

Pre-diagnosis, mean PCS (39.94 vs 39.54, p = 0.71) and mean MCS (52.03 vs 52.17, p = 0.82) scores were similar between NMIBC patients and matched non-cancer controls. Post-diagnosis, NMIBC patients had a significantly greater decrease in PCS compared with controls (-2.87 (95% CI -3.87, -1.86) vs. -1.47 (95% CI -1.93, -1.02), p = 0.02). Conversely, mean MCS change did not vary between groups (-1.79 (95% CI -2.76, -0.81) vs. -0.72 (95% CI -1.21, -0.23), p = 0.09). With respect to urinary function, NMIBC pts were more likely to have worsening of urinary leakage (38.0 % vs 18.7 %, p= < 0.01), require physician intervention for urinary symptoms (33.9 % vs 13.7 %, p= <0.01 ), and receive treatment for urine leakage (31.6 % vs 12.0 %, p= <0.01 ) compared with non-cancer controls (p = <0.01).

Conclusions

The diagnosis of NMIBC is associated with a significant decrease in physical HRQOL, including a significant impact on urinary symptoms and leakage. Further efforts to prospectively evaluate HRQOL in patients with NMIBC should be pursued to inform and improve patient counseling.

Funding

none

Introduction

Radical Cystectomy (RC) is subject to substantial morbidity and patients face complication rates as high as 64% at 90-days. Understanding the costs of complications after RC is essential to improving care. We studied the financial costs of different categories of complications after RC in order to identify drivers of expenditures.

Methods

Using the Premier Hospital Database we identified adult patients who underwent RC for bladder cancer from over 600 hospitals across the United States between 2003-2013. Ninety-day complications were captured using ICD9 codes. Complications were categorized according to Agency for Healthcare Research and Quality Clinical Classification Software. The primary outcome was cost of complication and secondary outcomes were mortality, length of stay (LOS), and discharge disposition. A generalized liner model conforming to a gamma distribution was used to evaluate cost data. Analyses were survey weighted, and all models were adjusted for patient (age, race, obesity, marital status, payer), hospital (bed size, teaching affiliation, rural, region), and surgery characteristics (lymphadenectomy, continent diversion, robotic, operative time, transfusion, surgeon volume, hospital volume) and clustered by hospital.

Results

We identified 9,137 RC patients, representing a weighting population of 57,553 patients. The top four most costly complications were venous thromboembolism (VTE $17547), soft tissue ($13523), gastrointestinal (GI $8663), and infectious (non-wound, i.e. sepsis, $7930) (p<0.001 for each). Pharmacy related costs were the primary driver of VTE costs. LOS was increased in each complication by 1.7 days for infectious, 4.5 days for soft tissue, 3.5 days for GI, and 3 days for VTE (p<0.001 for each). Being married, having fewer comorbidities, larger hospitals, teaching hospitals, shorter operations, lack of transfusions, high volume hospitals, and high volume surgeons were associated with statistically significantly lower costs of complications after cystectomy.

Conclusions

VTE, soft tissue, and GI complications are the most expensive complications after cystectomy, and thereby highlight potential candidates for future quality improvement initiatives.

Funding

None

Introduction

Radical cystectomy with urinary diversion is a standard treatment for high-risk non-invasive and muscle-invasive bladder cancer. Continent diversions (CD) may allow better quality of life and body image perceptions over ileal conduits (IC) in selected patients. Our aim is to study contemporary trends in the utilization of ICs and CDs in patients undergoing radical cystectomy.

Methods

Using ICD-9 codes, we identified in the National Inpatient Sample (NIS) from 2001-2012 all patients with the principal diagnosis of malignant neoplasm of bladder (188.x, 233.7) who underwent radical cystectomy (57.71) followed by either ileal conduit (56.61) or orthotopic neobladder/continent diversion (57.87). Patient sociodemographics, comorbidities and in-hospital complications, mortality, length of stay (LOS), and total cost after radical cystectomy with IC vs CD were compared. Chi square test and multivariable logistic regression were used to analyze patient and hospital characteristics. Student’s t-test and Wilcoxon rank sum test were used to evaluate continuous variables.

Results

Between 2001-2012, an estimated 69,049 ICs and 6,991 CDs were performed. The total number of CDs increased from 2001 to 2012 (p < 0.0001), but peaked in 2008 and subsequently declined every year thereafter. Patients of all ages received ICs at a higher rate than CDs (Table 1), including younger age groups (40-59 and 60-69). Males and Caucasians were more likely to have CD compared to females (p<0.001) and African Americans (p<0.0001), respectively. The rate of CDs was highest in the West (12.1%, p<0.001), at urban teaching centers (10.85%, p<0.001), and in large hospitals (9.71%, p<0.001). On logistic regression analysis, when accounting for age, gender, comorbidities, and hospital characteristics, ICs were associated with higher rates of overall (OR 1.06, p=0.0185) and infectious (OR 1.13, p=0.002) complications and in-hospital mortality (OR 1.87, p<0.0001). There was no difference in LOS between the two groups.

Conclusions

The number of CDs performed has declined since 2008. Patients of all ages, including young patients, are more likely to receive IC than CD. Gender, socioeconomic factors, and geographic location may influence diversion type. CDs are associated with comparable rates of complications and in-hospital mortality. Potential causes for declining incidence of continent diversions may include physician reimbursement, length of surgical time, and higher incidence of robotic surgery. These factors should be the subject for further study.

Funding

None

Introduction

To create a user-friendly, personalized decision support tool that can display the likelihood of readmission after radical cystectomy, as well as recommendations for optimal follow-up based on published data.

Methods

We developed the "REACT: Readmission Elimination App for Cystectomy Treatment" using Apple's Xcode. This tool uses delay-time analysis models to determine the optimal timing of office visits and phone calls in order to maximize the probability of detecting radical cystectomy patients susceptible to readmission. We calibrated and validated the tool using radical cystectomy patient data from the 2009-2010 Healthcare Cost and Utilization Project State Inpatient Databases, and our institution's bladder cancer database from 2007 to 2011, as published in J Urol. 2016 May;195(5):1362-7.

Results

Our decision support tool generates a forecasted probability of readmission as well as suggested follow-up frequencies. Sample screenshots from the tool are presented in the Figure. After inputting the date of hospital discharge and other patient characteristics, the app tracks the status of the patient, suggests an optimal follow-up strategy, provides patients with the ability to contact their provider by phone, and tracks future appointments.

Conclusions

We integrated a delay-time analysis methodology into a software tool that can run on personal computers, iPads and iPhones to improve follow-up of patients after radical cystectomy. This software generates real-time predictions of the likelihood of readmission and indicates when future follow-up should be performed, so as to identify clinical deterioration in a timely manner. Through further customization and pilot testing, this decision support tool will enable personalized follow-up to help prevent hospital readmission after radical cystectomy.

Funding

none

Introduction

Recent genomic studies suggest that urothelial carcinoma (UC) can be grouped into luminal and basal subtypes. Basal bladder cancers are enriched with squamous features and are associated with worse prognosis. Previously, we reported that Desmocollin2 (DSC2) is an immunohistochemical (IHC) marker of squamous differentiation (SD) in UC, that correlates significantly with advanced tumor stage and poor prognosis. Here, we examined the subtype classification of bladder cancer based on Uroplakin III (UPK3) and Cytokeratin 5/6 (CK5/6) expression.

Methods

Expression of UPK3, CK5/6 and DSC2 was measured by IHC in 57 cases of bladder cancer treated with cystectomy (data set-1:previously reported in IHC of DSC2), which included 39 cases of pure UC and 18 cases of UC with SD. Next, we confirmed the result in the other data set of 77 cases of muscle invasive bladder cancer treated with cystectomy from 2006 to 2015 (data set-2).

Results

In dataset-1, the positivity of UPK3, CK5/6 and DSC2 in pure UC was 46%, 21% and 0%, while the positivity in UC with SD was 0%, 83% and 100%, respectively. CK5/6 expression correlated with DSC2 expression, and UPK3 expression was mutually exclusive of both CK5/6 and DSC2 expression. In addition, the positivity of UPK3 and CK5/6 in papillary tumors was 43% and 14%, respectively, and in flat and non-papillary tumors was 28% and 49%, respectively. In normal urothelium, UPK3 expression was observed only in umbrella cells, while CK5/6 expression was detected only in the basal layer. The intermediate layer showed no staining with either marker. UPK3 positive cases had the most favorable cancer specific survival (CSS at 5 years; 83%), while CK5/6 positive cases had the worst prognosis (55%), and cases negative for both markers had an intermediate prognosis (68%)._x000D_ In dataset-2, the expression of UPK3 and CK5/6 in papillary UC was 57% and 4%, respectively, while expression in flat and non-papillary UC was 11% and 39%, respectively. CSS at 5 years was 95% in UPK3 positive, 49% in CK5/6 positive and 59% in marker-negative cases. _x000D_

Conclusions

While genomic subtyping of UC requires clustering of large datasets derived from an entire cohort of patients, our simple IHC with two markers of luminal and basal differentiation is capable of stratifying prognosis on an individual patient basis. IHC classification of UC lends itself to easy adoption in routine clinical practice.

Funding

none

Introduction

The 2015 UK NICE guidance (NG12) for &[prime]urgent suspected cancer&[prime] (USC) referrals suggested that asymptomatic microhematuria (AMH) need not be seen as USC._x000D_ _x000D_ We hypothesized that declining referrals for AMH was safe, and would help to address our unacceptably long wait for the one-stop hematuria clinic (OSHC). We present the outcome of rejecting referrals for AMH entirely for one year, the first study of its kind to adopt this innovative approach.

Methods

Hematuria referrals to a UK cancer center (catchment population >600K) were analyzed retrospectively prior to NG12 publication from July 14 to July 15 (cohort 1) and compared to prospective data following NG12 from July 15 to July 16 (cohort 2). After NG12, referrals for AMH were declined in writing. Bladder cancer was categorized as per the European Organisation for Research and Treatment of Cancer risk stratification.

Results

Over the study period, 1963 patients were seen in a OSHC; 1105 prior to NG12 (cohort 1), and 858 after (cohort 2). In cohort 1, 686 had gross hematuria (GH), 159 had symptomatic microhematuria (SMH), and 260 had AMH. Cancers were diagnosed in 132 cohort 1 patients; 83% (110 patients) had urothelial malignancies, of which 107 (97%) presented with GH or SMH, and only 3 with AMH. Twenty-six patients (23%) were diagnosed with high-risk non-muscle invasive bladder cancer (HRNMIBC), 21 patients (19%) with muscle invasive bladder cancer (MIBC), and 4 (4%) with upper tract TCC (UTTCC)._x000D_ _x000D_ In cohort 2, 137 cancers were diagnosed, of which 114 (83%) were urothelial malignancies. These included 26 HRNMIBCs (23%), 24 MIBCs (21%), 3 metastatic bladder cancers (3%), and 7 UTTCCs (6%). One-hundred and fifty-three referrals for AMH were rejected in writing during cohort 2._x000D_ _x000D_ By excluding patients with AMH from cohort 1, only 3 low-risk non-muscle invasive bladder cancers would have remained undetected after implementing NG12 (in addition to 2 small renal tumors). Furthermore, after NG12, the average time from referral to first appointment fell from 35 days in July 15, to 17 days in July 16 (up to 50% reduction)._x000D_

Conclusions

Prior to NICE guideline NG12 implementation, no significant cancers were detected in patients referred with AMH in our study. After NG12, and rejecting referrals with AMH entirely, patients with bladder cancer were seen and treated earlier._x000D_ _x000D_ While such a novel approach to AMH may attract criticism, this study outlines for the first time, that declining to accept such referrals in a state-funded healthcare system is an effective approach for rationalization of resources.

Funding

None

Introduction

Bladder cancer (BCa) is one of the top ten most common cancers in the world. However, very few studies have reported on health disparities involving advanced BCa. The objective of this study was to identify disparities in treatment and survival for patients with metastatic bladder cancer.

Methods

Patients with metastatic BCa diagnosed between 1991 and 2014 were identified through the California Cancer Registry. Included in the analysis were age at diagnosis, sex, race/ethnicity, area-based socioeconomic status (SES), first course of treatment, and survival time. Predictors of treatment were identified using logistic regression, and cause-specific survival was analyzed using Cox regression.

Results

A total of 3,073 cases of metastatic BCa were identified. Among these cases, 67.39% were male, and 32.61% were female. The race distribution was 74.78% non-Hispanic (NH) white, 6.25% NH black, 12.46% Hispanic and 5.96% NH Asian/Pacific Islander (Asian/PI). Among all patients presenting with metastatic bladder cancer, 45.6% received chemotherapy. Of those receiving chemotherapy, 42% underwent additional local treatment (radical cystectomy or radiotherapy). Patients over age 65, female patients and those residing in all but the wealthiest census tracts were less likely to receive chemotherapy with or without local treatment. NH black patients also were slightly less likely to be treated. Patients diagnosed between 2003 and 2014 were 32% more likely to receive chemotherapy than those diagnosed between 1991 and 2002 (p<.001). Overall and cause-specific survival for the entire cohort was 11.1% and 14.5%, respectively. A smaller proportion of NH black patients survived two years after diagnosis (6.5% versus 14.4% NH white, 18.3% Hispanic, and 15.4% Asian/PI). After adjustment for other factors, patients aged 80 and older were more likely to die from bladder cancer (HR=1.2, 95% CI=1.0-1.3) as were black patients (HR=1.2, 95% CI=1.0-1.5). Patients residing in poorer census tracts were slightly more likely to die of bladder cancer although results were not statistically significant. Patients who received no chemotherapy had more than twice the risk of death. There was no evidence that overall survival improved in the most recent time period.

Conclusions

Non-Hispanic blacks and patients who were not treated with chemotherapy experienced poorer survival than other groups. There had been no improvement in this heath disparity or in overall survival over the last two decades.

Funding

None

Introduction

Bladder Cancer (Bca) is significantly associated with aging. However, the correct management of BCa in the elderly remains controversial. The aim of the study is to analyse predictive factors of early death in a group of patients >70y, with Bca, at 100 days after a geriatric comprehensive assessment (CGA), in order to help in therapeutic decision making.

Methods

112 patients with Bca were enrolled. This is a multicentric and prospective cohort study approved by an ethics committee. A standardized comprehensive geriatric assessment (CGA) was done before the treatment decision and different geriatric data were collected: MMSE, MNA, BMI, Grip hand grip strength, ADL, IADL, GIRSg, Gait speed, QLQC30, Charlson, G8 and Balducci classification. Characteristics of cancer, social and demographic data were also collected. During a 100-days follow up, the rate of death, treatments made and geriatric interventions were collected.

Results

A total of 112 patients were enrolled, including 25,9 % of women and a mean age of 82y [70-96]. 26,8% (n=30) of patients died within the 100-days follow up. 34,8%(n=39) of patients had metastatic cancers. The most common proposed treatments, by the surgeron or the oncologist, were surgery (radical cystectomy) (44,6%) and chemotherapy (41,6%). In 35,7% of cases, CGA has modified the therapeutic decision, in favor to palliative care in 57,5%._x000D_ In univariate analyzes, metastatic cancers (HR= 2,7 [ 1,3-5,5],p=0,008), cognitive deficit (MMSE<24) (HR=3;2[1,5-7],p=0,003), confusion (HR=2,2 [1,1-4,5],p=0,032), under nutrition (MNA<17) (HR=6,9 [2,1-22],p<0,001), lower gait speed (HR=5,6 [2,4-12,9],p<0,001), social isolation (HR=4,5 [2,1-9,6], p<0,001), and loss of autonomy in ADL (HR=2,7 [1,1-6,2],p=0,023) and IADL (HR=2,7 [1,1-6,5],p=0,032) had significantly more risk of dying. The predictive factors of early death, in multivariate analyzes, were the metastatic cancers (HR=3,5 [1,6-7,5], p=0,002), the lower gait speed (HR=3,1 [1,2-7,7], p=0,015), social isolation (HR= 2,6 [1,2-5,9], p=0,02)and loss of autonomy in ADL (HR=3,3 [1,2-9,2],p=0,022)._x000D_ _x000D_

Conclusions

This study confirms that some geriatric data could be predictive of worse outcome. These results can help the geriatrician, the surgeon and the oncologist in decision making. But these data also encourage to propose targeted geriatric interventions to improve the patients’s prognosis, especially customize their perioperative care.

Funding

none

Introduction

Ureteroenteric anastomotic strictures (UAS) are a known long-term complication of radical cystectomy with urinary diversion (RCUD). Often a silent process, UAS can be associated with progressive renal function decline, and often require additional procedures. We assessed our series of RCUD to determine predictors of UAS.

Methods

We completed a retrospective review of consecutive patients who underwent RCUD between 2005-2015 by a single surgeon. All ureteroenteric anastomoses were performed in a freely-refluxing end-to-side fashion over an 8Fr feeding tube. Kaplan-Meier time-to-event analysis was performed to estimate the cumulative incidence of UAS, with patients censored at last follow-up or death. Univariable and multivariable logistic regression were performed to identify predictors of UAS. The final multivariable model was selected using Akaike Information Criterion to optimize model parsimony and fit. _x000D_

Results

RCUD was performed in 286 bladder cancer patients, with a median age of 69.9 years (IQR 62.8-76.2) and median follow-up of 21.4 months (IQR 8.9-42.3). Urinary diversions included ileal conduit (164, 57.3%), orthotopic ileal neobladder (114, 39.9%), and continent cutaneous reservoir (8, 2.8%). _x000D_ UAS developed in 29 patients (10.1%), at a median of 6.4 months (IQR 4.4-8.8) postoperatively. The cumulative incidence of UAS was 12.5% (95% CI 8.7-17.7) at 24 months. UAS patients had higher rates of obesity (72.4% vs 28.0%, p<0.001), were younger (66.4 vs 70.3 years, p=0.003), and had a longer median follow-up (34.0 vs 20.2 months, p=0.04). There was no difference in preoperative radiation in the UAS group (3.5% vs 10.3%, p=0.2). _x000D_ On time-to-event analysis, obese (BMI ≥30) patients had a higher cumulative incidence of stricture than non-obese (25.2% vs 5.9%, p<0.001) at 24 months (Figure). On multivariate analysis, only obesity was an independent predictor of UAS (OR 6.4, 95%CI 2.6-156; p<0.001)._x000D_

Conclusions

Ureteroenteric anastomotic strictures are often a silent event arising within the first year of radical cystectomy with urinary diversion. Obese patients are at a significantly increased risk of stricture development, regardless of urinary diversion type or oncologic characteristics.

Funding

None

Introduction

Nested variant (NV) urothelial cell carcinoma (UCC) is a rare histological subtype of UCC with benign features. There is limited data on the outcomes and characteristics of patients with this histology (largest study with 52 patients); however, it has traditionally been viewed as a more aggressive subtype of UCC and neoadjuvant chemotherapy is not recommended. Our primary interest was to assess whether there is a difference in overall survival (OS) after radical cystectomy (RC) between patients with NV features compared to patients with pure UCC.

Methods

We identified 1949 patients who underwent RC between January 1995 and December 2015 and had pure UCC or NV. We utilized a univariate and multivariable Cox proportional hazards model, adjusting for gender, positive lymph node invasion status, neoadjuvant chemotherapy, age and tumor stage at cystectomy to assess whether there was a difference in OS between UCC and NV patients. To determine whether there were differences in demographics and tumor characteristics between patients with NV and those without, group comparisons were made using Fisher’s exact test for categorical variables and Wilcoxon rank?sum test for continuous variables. Lastly we utilized the Cochran?Mantel?Haenszel method stratified on histology and applied the Breslow?Day test for homogeneity to evaluate whether there were differences in response to neoadjuvant chemotherapy based on histology.

Results

We identified 1807 (93%) pure UC patients and 142 (7.3%) patients with nested features. Among our 1949 patients, 919 with pure UCC and 77 with NV, died from any cause. The median follow up time for survivors was 4.6 years from RC. A larger proportion of NV patients at time of RC had lymph node invasion (p=0.007) and worse pathological tumor stage (p < 0.001) than pure UCC. On univariate analysis NV was associated with poorer OS (HR 1.26; 95% C.I. 1.00, 1.60; p = 0.049); however, on multivariable analysis, the association between histology and OS is no longer significant (HR 0.96; 95% CI 0.75, 1.22; p=0.7). We did not find a significant difference in response to neoadjuvant chemotherapy between the two histological groups (p = 0.6).

Conclusions

NV carcinoma presents at a higher stage than pure UCC at time of RC, but does not necessarily represent a more aggressive variant. It perhaps represents a delay in diagnosis due to NV benign features.

Funding

None

Introduction

Current guidelines for surveillance after radical cystectomy (RC) are based on pathologic stage and do not take into account other patient specific factors. We previously reported Weibull models determining duration of cancer surveillance. We now present a novel surveillance protocol outlining the frequency and duration of follow-up based on stage specific recurrence risk and competing risks of non-cancer mortality.

Methods

We identified 2205 patients who underwent RC for urothelial carcinoma (UC) at the Mayo Clinic from 1980 to 2010. The risks of abdomen/pelvis and chest recurrence were estimated using accelerated failure-time (AFT) models, stratified by pathologic stage (pT0, pTa/Cis/1, pT2, pT3/4, pTanyN+). Similarly, the risks of non-cancer death according to age (<60, 60-69, 70-79, >80) and Charlson comorbidity index (CCI <1 versus ≥1) were also calculated. Surveillance intervals were calculated for each conditional 1%, 3%, and 5% recurrence risk increase up to 10 years follow-up. Specific surveillance recommendations balance estimated risk of non-cancer death with recurrence risk where allowable recurrence risk is up to the risk of non-cancer death.

Results

At a median follow-up of 4.7 years (IQR 1.1, 10.3), disease recurrence was diagnosed in 852 (38.6%) patients. Using AFT models for recurrence, surveillance intervals for all stage, age, and comorbidity risk groups were generated. The surveillance strategy (e.g. 1%, 3%, or 5%) for an individual patient is selected based on probability of non-cancer specific mortality as determined by age and CCI (Tables 1 and 2). For example, a patient less than 60 with CCI ≤ 1 would follow a 1% recurrence risk schedule for the full 10 years. Conversely, a patient age 60-69 with a CCI > 1 would follow a 5% schedule for the full 10 years.

Conclusions

Using AFT modeling we have developed a risk-adapted protocol for surveillance frequency and duration after RC taking into account both the risk of recurrence and the risk of non-cancer mortality.

Funding

None

Introduction

To provide a population-based assessment regarding utilization and timing of radical cystectomy (RC) according to gender.

Methods

A total of 49,974 patients aged 66 years or older diagnosed with clinical stage TI-IV N0M0 bladder cancer from January 1, 2001 to December 31, 2011 from SEER-Medicare data were analyzed. We used multivariable regression analyses to identify factors predicting the use and delay of radical cystectomy. Cox proportional hazards models were used to analyze survival outcomes.

Results

Of the 49,974 patients diagnosed with bladder cancer 13,015 (26.0%) were female. Women were significantly more likely to undergo RC across all stages compared to their male counterparts (Stage I: Relative Risk (RR) 1.53, 95% Confidence Interval (CI) = 1.27-1.84, p < 0.001; Stage II: RR 1.52, 95% CI = 1.37-1.70, p < 0.001; Stage III: RR 1.26, 95% CI = 1.15-1.39, p < 0.001; Stage IV: RR 1.37, 95% CI = 1.17-1.47, p < .001). Moreover, there was no significant difference in delay to RC except women with Stage IV disease were less likely to have delay to RC than men (RR 0.67, 95% CI = 0.62-0.95, p=0.017). Using propensity score matching, women had improved overall (Hazard Ratio (HR) 0.85, CI 0.82-0.88, p < 0.001), but worse cancer-specific survival (HR 1.08, CI 1.02-1.15, p = 0.008) than men, respectively.

Conclusions

Gender differences persist with women significantly more likely to undergo RC independent of clinical stage. However, women have significantly worse cancer?specific survival than men. Delay from diagnosis to surgery did not account for this decreased survival among women.

Funding

This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a by a Clinical and Translational Science Award Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health, Comparative Effectiveness Research on Cancer in Texas (CERCIT) (RP140020) and the National Cancer Institute (NCI) (K05 CA134923) (SBW) and in part by the fellowship from University of Texas MD Anderson Cancer Center's Halliburton Employees Foundation (JH).

Introduction

Perioperative morbidity is common amongst patients undergoing radical cystectomy. Frailty (decreased functional reserve) measurement has been proposed to identify at-risk patients, but there has been limited comparative prospective analysis of different frailty measures.

Methods

98 cystectomy patients at our institution from January 2015 to September 2016 were prospectively evaluated preoperatively, using the protocols for the four frailty indices: Duke Activity Status Index (DASI), Edmonton Frailty Index (EFI), Fried Frailty Index (FFI) and Schonberg Mortality Index (SMI) by a urology resident. Consensus Statement malnutrition assessment was performed by a dietitian. We examined the relationship between frailty, patient characteristics (age, neoadjuvant chemotherapy, malnutrition), and outcomes (length of stay 30-day readmission, 30-day Clavien grade > 2) were examined.

Results

Median DASI was 39.4 (IQR: 26.9, 58.2), median EFI was 3 (IQR: 2, 4.2), median FFI was 2 (IQR: 1, 3), and median SMI was 12 (IQR: 9.7, 15). The median age of cystectomy patients was 71 years (IQR: 62, 77). 66 of 98 (67.3%) patients underwent neoadjuvant chemotherapy while preoperative malnutrition was present in 32 of 98 (32.6%) patients. With respect to outcomes: median length of stay was 7 days (IQR: 5, 8), 30-day readmission rate was 25.8%, and the 30-day complication rate was 41.8%. The associations of variables with the four frailty indices are displayed in Table 1. Increased age was significantly associated with all four indices. Neoadjuvant chemotherapy was only associated with the FFI (p=0.04). The presence of malnutrition was associated with the EFI (p=0.02), FFI (p<0.01), and SMI (p=0.04). The SMI was only index related to postoperative outcomes, as increased SMI was associated with both 30-day complications (p=0.04) and 30-day readmission (p<0.01).

Conclusions

Different frailty indices appear to measure different aspects of functional status. In this prospective evaluation, frailty was associated with age, malnutrition, and complications to varying degrees. The SMI was the strongest predictor of readmission and postoperative complications in patients undergoing cystectomy. Evaluation of patients preoperatively can be used to better counsel patients about postoperative complication risk._x000D_

Funding

American Cancer Society Seed Grant.

Introduction

End stage renal disease patients on hemodialysis (HD) have in increased risk of developing bladder cancer, which is more likely to present in an advanced stage. These patients also have significant risk of non-cancer related morbidity and mortality, especially from cardiovascular disease. Radical cystectomy (RC) is the standard of care for non-metastatic muscle invasive bladder cancer, but is associated with significant morbidity. Despite this high risk scenario, very little is known regarding outcomes in HD patients following RC._x000D_

Methods

The US Renal Disease System database was used for this study, which is a prospective database which includes every HD patient in the United States. A retrospective review of all HD dependent patients who underwent radical RC for bladder cancer between 1989-2013 was performed. Competing risks analysis was used to estimate overall and disease specific survival. Cox regression was used to identify predictors of death.

Results

During the 25-year study period, a total of 1594 patients were identified for analysis, of whom 76.1% were male. The mean age was 70.4 ± 9.8 years. Mean length of stay was 16.2 ± 14.8. Concurrent nephrectomy was undertaken in 33.1% of patients. The 30-day mortality rate was 5.9%. Overall 1, 3, and 5-year survival was 58.4%, 31.4%, and 19.6% respectively. Bladder cancer specific survival at 1, 3, and 5 years was 89.3%, 82.3%, and 80.0% respectively. Predictors of overall mortality were age (HR, 1.03; 95%CI, 1.02-1.03), history of congestive heart failure (CHF) (HR, 1.19; 95%CI, 1.03-1.38), history of diabetes (HR, 1.22; 95%CI, 1.04-1.42), concurrent nephrectomy (HR, 1.09; 95%CI, 1.03-1.14), and female sex (HR, 1.15; 95%CI, 1.01-1.33). Amount of time on HD prior to RC was not predictive of mortality. _x000D_

Conclusions

This represents the largest study to date evaluating outcomes following RC in HD patients. RC is associated with significant morbidity and less than 20% of patients survive 5 years. Older patients, female patients, and those with a history of CHF or diabetes are at an increased risk of mortality._x000D_

Funding

none

Introduction

Our group has previously demonstrated that blood-based tumor markers can be useful clinical outcome predictors for non-muscle invasive urothelial carcinoma of the bladder (UCB) Our aim in this study is to further evaluate the predictive value of CEA, CA 19-9 and CA 125 on disease recurrence and progression. _x000D_

Methods

We prospectively included 328 consecutive patients between February 2008 and August 2014 to measure preoperative serum levels of CEA, CA 19-9 and CA 125 before first transurethral resection of the bladder (TUR). Institutional Ethical Committee approval was obtained prior to this study. Patients diagnosed with pT2 UBC were excluded (42), leaving 286 patients for analysis of recurrence or progression. After first TUR, patients were followed with routine cystoscopy, cytology and ultrasound every 6 months. All patients with non-muscle invasive (NMI) bladder cancer with high-grade disease, previous recurrence, carcinoma in situ (CIS) or T1 received induction and maintenance intravesical BCG.

Results

We found that CEA and CA 19-9 levels were significantly higher in patients who had either tumor recurrence and/or progression compared to those who had no UBC recurrence during follow-up (p=0.02; p=0.03). As we had found previously, however, CA 125 levels did not differ between the two groups (p=0.42). Overall, mean CEA level was 2.1 (0.2-12.8), CA 19-9 was 17.1 (0.4-189.9) and CA 125 was 12.5 (1.2-103.9). In patients who presented tumor recurrence and/or progression, mean CEA was 5.5, mean CA 19-9 was 21.0 and CA 125 was 13.8, while in the non-recurring group, mean CEA was 3.1, mean CA 19-9 was 11.1 and CA 125 was 11.3. Mean follow-up was 4.9 years. Patients were 70.3% males (201); 63.3% (181) of patients had pTa at first TUR. Concomitant carcinoma in situ was present in 25 cases (8.7%).

Conclusions

Biomarkers utilized in routine follow-up of other malignancies, such as CEA and CA 19-9, can also be included in UCB management, since it proved able to distinguish a higher risk group of patients that could be managed accordingly. Future studies may add these blood-based tumor markers to a predictive model and validated in a larger cohort. Although CA 125 was not significantly associated with oncologic outcome, further studies are required before excluding this potential biomarker in UBC.

Funding

none

Introduction

There is limited information regarding the association between smoking intensity and survival trends among patients with bladder cancer (BC). We examined demographic and survival trends for patients diagnosed with BC stratified by smoking intensity._x000D_

Methods

The Florida Cancer Data System (FCDS) linked with US census data was used to identify all smoking adult patients ?18 years residing in Florida diagnosed with BC between 1981 and 2009. Median and 5-year overall survival rates were compared between patients that smoked <1, 1-2, and >2 packs of cigarettes per day (PPD). A multivariable Cox regression model was used to determine the adjusted hazard ratio (AHR) along with 95% confidence interval (95% CI) for mortality after adjustment for age at diagnosis, sex, race, ethnicity, socioeconomic status (SES), marital status, regional lymph node positvity, treatment, grade, and stage of BC. _x000D_

Results

Of the 14,077 smoking BC patients, 25%, 63%, and 12% smoked <1, 1-2, and >2 PPD, respectively. The majority of patients were males (74%), Whites (96%), living in an urban area (94%), and with a middle-high/highest SES (53%). The majority of them had localized BC (73%). Median overall survival and 5-year survival rates for the entire cohort were 4.0 years and 43.7% (95%CI: 42.7-44.7), respectively. Median overall survival for patients smoking <1, 1-2, and >2 PPD was 4.2 years, 3.9 years, and 4.1 years, respectively. The 5-year survival rates for patients smoking <1, 1-2, and >2 PPD were 45.1% (43.1-47.1), 43.1% (41.8-44.3), and 43.6% (40.9-46.3), respectively. Patients smoking 1-2 PPD ([HR] 1.11; 95% CI 1.06-1.16, p<0.001) and >2 PPD ([1.08] 1.00-1.16, p=0.042] were significantly more likely to have a higher risk of mortality compared to patients that smoked <1 PPD on multivariate analysis._x000D_

Conclusions

Higher smoking intensity is associated with an increased risk of mortality among patients with BC. These data highlight the importance of smoking cessation for BC patients and underscore the need for patient education regarding the dangers of smoking. Smoking cessation efforts should be targeted to this population since even a small reduction in the amount of smoking may still have potential survival benefit.

Funding

None

Introduction

No serum prognosticator has been established in patients with potentially lethal bladder cancer. The aim of this study is to evaluate the prognostic impact of serum CYFRA 21-1 (CYFRA) in these patients compared with classic tumor markers.

Methods

Serum levels of CYFRA and other classic tumor markers: CA19-9, SCC, and C-reactive protein (CRP) were measured in 66 patients with T1G3 (n = 20) or muscle invasive bladder cancer (n = 46) without metastasis between Jan 2011 and Aug 2015. Cut-off values of the tumor markers were determined by receiver operating characteristic analyses. Prognostic values of age, gender, T stage, hydronephrosis, albumin, hemoglobin, CA19-9, SCC, CRP, and CYFRA were evaluated using multivariate analysis with a Cox proportional hazards model.

Results

The median (range) value of CYFRA was 2.6 (1.1-34) ng/mL. The median follow-up period was 24.3 (1.1-58.1) months. Prognostic values of age (< 73 vs. ≥ 73), T stage (< T2 vs. ≥ T2), hydronephrosis (absence vs. presence), albumin (cut-off 4.0 g/dL, median), hemoglobin (cut-off 12.7 g/dL, median), CA19-9 (cut-off 21 U/mL), SCC (cut-off 1.5 ng/mL), CRP (cut-off 0.1 mg/dL), and CYFRA (cut-off 3.5 ng/mL) were evaluated dichotomously. Multivariate analyses revealed that CYFRA (p = 0.017) was the only significant and independent predictor of cancer-specific survival. Risk of cancer-specific mortality was 4.48-fold (95% CI, 1.37-18.27; p = 0.012) higher in CYFRA-high patients than in CYFRA-low/either classic tumor marker-high patients._x000D_ _x000D_ Figure. Cancer-specific survival curves according to CYFRA and classic tumor markers status

Conclusions

The current results indicated that cancer-specific mortality of non-metastatic bladder cancer could be better predicted by CYFRA than other previously reported tumor markers. Further prospective analyses will be needed to confirm our results.

Funding

none

Introduction

Muscle-invasive bladder cancer (MIBC) and its treatment are associated with high morbidity and mortality. The concentration of care in tertiary centers is believed to improve patient outcomes but the potential negative impact of travel distance on quality of care and survival is unclear in MIBC as it may be associated with delay in diagnosis, decreased access to multimodal care and difficulty in managing the complications associated with care. Using data from the National Cancer Data Base (NCDB), we evaluated the association between distance to treating facility and overall mortality in patients with MIBC.

Methods

Data were obtained from NCDB 2004-13. We evaluated all cause mortality for patients with MIBC (T2-T4a, N0, M0), stratified by travel distance to treatment facility in 3 categories: <12.5, 12.5-49, 50-250 miles. Cox proportional hazard models were fit in the overall population, then in subgroups according to treatment facility type. A secondary analysis was done examining the interaction between distance and facility type.

Results

34,729 patients with MIBC identified. The three groups included 20,234 (58.3%), 10,400 (29.9%), 4,095 (11.9%) patients living <12.5, 12.5-49, 50-250 miles from their treatment facility, respectively. Kaplan -Meier curve constructed for overall survival separated by distance (Figure 1). HRs for distance and mortality are reported in table 1. There was a trend towards decreased probability of mortality as distance to facility increased; this relationship was significant when traveling a long distance for care at an academic facility .

Conclusions

Lengthy travel distance to treating facility was not associated with decreased survival in patients with MIBC. In contrast, travel distance was associated with improved overall survival if the treatment facility was an academic center.

Funding

None

Introduction

Positive surgical margins (PSM) after RP are a known factor associated with BCR. Radiation therapy (RT) currently represents an established option for metastasis-free patients. However, the timing of administration is not univocal._x000D_ The aim of this study is to identify factors related to the indication to adjuvant radiation therapy (aRT) vs salvage (sRT), taking a picture of the contemporary management and prognosis of patients with PSM after radical prostatectomy (RP) at an academic tertiary institution.

Methods

We retrospectively reviewed our perspectively-maintained database. RP has been performed with an open retropubic approach until 2010, then with a robotic transperitoneal one._x000D_ All the cases with PSM and adverse pathological features (stage ≥pT3, GS ≥8) were submitted to a multidisciplinary discussion. The indication to sRT was given if biochemical recurrence (BCR, PSA 0.2 ng/ml), preferably before PSA >0.5 ng/ml._x000D_ Logistic regression models were used to determine the factors associated with RT indication and BCR in univariate and multivariate analysis. The BCR-free survival was calculated using Kaplan-Meier method.

Results

Out of 789 patients, 197 had PSM (overall prevalence 25,2%), with monofocal involvement in 121 (60.8%) and multifocal in 78 (39.2%). _x000D_ An aRT was indicated in 40 patients (20.3%). Findings are summarized in table 1. Factors independently related to aRT indication were: pathological stage, number of sites of PSM and post-operative PSA. The median follow-up time was 51.1 months (IQR 30.9-69.3). Among the 157 patients for whom aRT was not indicated, 39 experienced a relapse of PSA (prevalence of BCR 24.8%, p not significant). 26 were then treated by sRT, 8 by androgen deprivation therapy, 5 underwent surveillance. Overall, a BCR was found in 46 patients (23.4%) after a median time of 24.0 months (IQR 18.0-36.0)._x000D_ At the last available control 176 patients (89.3%) had a PSA < 0.2 ng/ml (median value 0.02). Only pathological stage was significantly related to the risk of BCR.

Conclusions

In a real-life scenario, the indication to aRT is more restrictive than what recommended by guidelines and is driven by the amount of PSM and a detectable post-operative PSA. No differences in BCR free survival are evident in patients with PSM submitted to aRT vs sRT.

Funding

none

Introduction

Level one evidence and current NCCN guidelines recommend adjuvant radiotherapy (ART) for patients with adverse pathologic features following radical prostatectomy. Salvage radiotherapy (SRT) administered upon detection of biochemical recurrence may be an appropriate alternative limiting overutilization of radiotherapy in the majority and cost?effective. We sought to describe our outcomes using salvage radiotherapy.

Methods

A total of 1,269 consecutive patients diagnosed with localized prostate cancer who underwent robot?assisted radical prostatectomy (RARP) from 2002 to 2013 were included. Biochemical recurrence was defined as 0.2 ng/mL or greater on 2 consecutive visits following surgery. Primary outcomes included BCR, prostate cancer specific mortality (PCSM), and overall mortality (OM). Cost estimates for radiotherapy administered were calculated based on 2016 Medicare reimbursement rates.

Results

Of the 1,269 men who underwent RARP at median follow?up of 5.0 years, 227 (17.9%) men had BCR. According to NCCN guidelines, ART was recommended to 436 (34.4%). Of these eligible patients, 273 (62.6%) had no ART with no subsequent BCR; 84% had follow?up exceeding 2 years. The remaining 163 (37.4%) men did have BCR of which 32 (2.5%) received ART concurrent with androgen deprivation therapy. The remaining had salvage therapy including 27 (2.1%) with SRT alone (Table 1). Overall and PCSM was 59 (4.7%) and 18 (1.4%), respectively. Medicare expense for ART is $37,130.85. Following NCCN guidelines would equate to an additional $10 million in radiotherapy costs in men with no subsequent BCR. Given >80% in this NCCN ART group with no evidence of disease 2+ years, the risk of further progression in the ART group is minimal (<10%).

Conclusions

For men with adverse pathologic features the risk of overtreatment with ART ranged from 67?85%. These outcomes are consistent with prior reports suggesting utilization of SRT may be more cost effective and have comparable outcomes to ART. These results support current clinical trials underway discerning the utility of SRT in men with adverse pathologic features.

Funding

none

Introduction

Limited data exist regarding urinary continence after post-radical prostatectomy (RP) intensity modulated radiation therapy (IMRT) and whether IMRT influences urinary continence or interfere with the recovery from RP when given early.

Methods

118 men were treated with curative-intent RT after RP. Forty-three men (36%) received adjuvant RT (13%) and early salvage (23%) within the 1st year from surgery and 75 men (64%) received late salvage RT (>1year from RP). Quality of life measures were prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC-26) by patients at baseline and at follow-up times. Each group (early and late RT) was compared to a control group from our prospective collected RP cohort that did not had RT based on age at RP, BMI, pre-operative incontinence scores and post-operative incontinence scores and pad usage. The control group included 248 men with a median follow-up time of 44 months. Due to differences in stage of the RP and RT cohorts, it was not possible to control for sparing of the neurovascular bundles. Endpoints are pad usage and incontinence score.

Results

With a median follow-up time of 60m, in men treated with IMRT, 29 patients (25%) deteriorated in pad usage, 14 (12%) improved and 75 (63%) were stable. Deterioration in continence was correlated with poor baseline incontinence scores (p<0.001) and with pre-RT number of pad usage per day. Of the patients that scores 100 in the incontinence score, only 3% deteriorated in continence. _x000D_ In the early (<1 year) RT group, mean incontinence score improved from 57 to 72 (p<0.01) and in the late RT group, mean incontinence score deteriorated from 80 to 69 (p<0.001) and was associated with a 13% deterioration in pad-free rates (p<0.05). _x000D_ Comparison to the control group showed a 12% and 5% differences in pad-free status in the late RT group and the early RT group respectively. Comparison of the entire cohort to the control group showed a 10% higher pad free rate in the control group - 74% Vs. 64% (p<0.001) (figure 1) _x000D_

Conclusions

Late salvage RT caused 12% deterioration in pad-free status._x000D_ With the limitations of our control group, comparison to the cohort group showed 10% lower pad free rates after post prostatectomy RT. _x000D_ Deterioration in continence is strongly associated with the baseline urinary function._x000D_

Funding

none

Introduction

Our institution is a high volume center of radiotherapy for prostate cancer patients (PCaPts). We have performed either neoadjuvant androgen deprivation therapy (NADT), followed by external-beam radiation therapy (total 39 Gray) and high dose-rate brachytherapy (HDR-B, total 18 Gray) (NEH) or radical prostatectomy (RP) on high-risk PCaPts, as defined by prostate specific antigen (PSA) level (>20ng/mL), pathology of biopsy specimen (Gleason score [GS]: ≥8), and/or clinical staging (≥T3). No comparative studies have been reported for NEH and RP. In order to determine if NEH is a better therapy than RP, we compared biochemical recurrence-free survival (bRFS, i.e., post therapeutic PSA elevation) and overall survival (OS) between NEH and RP on high-risk PCaPts.

Methods

Between 2007 and 2012, 192 and 167 high-risk PCaPts were treated by NEH and RP, respectively. Biochemical failure (BF) for NEH was defined using Phoenix definition: any PSA increase of >2 ng/mL higher than the PSA nadir value, regardless of the PSA nadir value. Whereas BF for RP was defined as PSA values of >0.2 ng/mL. Of note, PSA of 18 RP-cases (10.8 %) did not decrease to less than 0.2 ng/mL. In these cases, the day of PSA nadir was defined as BF date. Difference between bRFS and OS were calculated using Kaplan-Meier method and log-rank tests.

Results

The median follow-up duration was 58.7 months. Age was significantly older in NEH group (median [interquartile range] = 71.9 [67.3-75.3] years) than in RP group (69.0 [64.9-72.3] years, p< 0.001, Mann-Whitney U test [MWU]). Initial PSA was higher in NEH (20.0 [10.1-43.6]) than RP group (15.9 [8.1-24.7] ng/dL, p<0.01, MWU). RP group had a trend of higher GS (72.1%) than NEH group (62.5%, p=0.07, chi square test). T stage was similar (NEH [66.1 %] vs RP [66.4 %], p=0.928, chi square test). The 5- and 7-year bRFS rates in NEH group (0.79 and 0.76, respectively) were significantly higher than those in RP group (0.51 and 0.41, respectively, p<0.001 each, Fig. 1A). However, in OS, no significant difference was found (p=0.838).

Conclusions

We retrospectively compared clinical outcomes of NEH and RP, and found that NEH might be as effective as RP for high-risk PCaPts. Currently, we are preparing prospective randomized case study comparing NEH and RP by adjusting age, GS, PSA, and T stage.

Funding

none

Introduction

Men diagnosed after prostatectomy with seminal vesicle invasion often have external beam irradiation (EBRT) as adjuvant treatment. Typically, men treated with radiation do not have assessment or treatment for T3b because it is often not detected. We report our results of seminal vesicle biopsy (SVB) in men with higher risk features planning to undergo permanent seed implant (PSI) followed by EBRT.

Methods

Of 1981 men who treated by PSI and followed 5-22 years (mean 10), 615 (31%) with high risk features had 6 TRUS guided biopsies of the SV (3 from each side). Patients with +SVB underwent laparoscopic pelvic lymph node dissection and those with positive nodes, bone or CT scans were excluded from implantation. 3 months of hormone therapy (NHT) was followed by Pd-103 implant to the prostate (dose 100 Gy) and proximal SV and 2 months later 45 Gy of conformal or image guided EBRT to prostate and SV only. NHT was given a median of 9 months. Within 2 months after treatment CT-based dosimetry was done with radiation doses converted to the biologic effective dose (BED). Biochemical freedom from failure (BFFF) was computed by the Phoenix definition, freedom from metastasis (FFM) in men with BF by absence of a positive bone or CT scan and cause-specific survival (CSS) by freedom from death in men with clinical recurrence. Association of risk features to +SVB were compared by chi-square and linear regression (LR). Survival was computed by Kaplan-Meier estimates with comparisons by log rank and Cox hazard rates (HR).

Results

53/615 (9.4%) had +SVB. Higher stage, Gleason score (GS) and PSA were associated with a positive SVB (p<0.001). LR demonstrated significance for stage (p<0.001) and GS (p=0.001). BED was higher in patients receiving a SV implant (202. Vs. 179.3 Gy2, p<0.001). BFFF, FFM and CSS was worse for +SVB (all p<0.001). 48/53 (90.6%) with +SVB had NCCN3 (high risk) status. BFFF in these men without and with a +SVB was 88.5 vs. 74.9%, 75.3 vs. 62.2% and 70.3 vs 62.2% at 5, 10 and 15 years (p=0.023). FFM was 99.3 vs. 89.6%, 96.5 vs. 84.4% and 94.9 vs. 75% (p<0.001) and for CSS was 99.6 vs. 97.8%, 96.4 vs. 82.1% and 91.3 vs. 65.7% (p<0.001). CSS by BED < 180 vs ≥ 180 Gy2 was 55.6 vs. 76.9% (p=0.406). In these high-risk patients, prostate cancer death was 40/314 (12.7%) for men with -SVB and 8/21 (38.1%) for +SVB (OR 4.22, 95%CI 1.6-10.8). Cox HR demonstrated GS (p=0.001, HR 1.9), BED (p=0.05, HR 0.991) and +SVB (p<0.001, HR 0.125) as significantly associated with CSS.

Conclusions

Men who have pT3b disease have inferior BFFF, FFM and CSS. Advanced stage and high GS are highly associated with a +SVB. Higher radiation dose is associated with improved CSS in the pT3b patients. Taken together these data suggest SVB should be performed in men presenting with high GS and stage when considering combination radiation therapy. When performing PSI, implantation of the SVs will increase dose and improve long-term cause-specific survival.

Funding

none

Introduction

Very high grade prostate cancer is associated with poor outcomes. We report on the long-term outcomes of men with Gleason score (GS) 9-10 prostate cancer treated by prostate brachytherapy (PSI) and external beam irradiation (EBRT).

Methods

Of 1981 men who were treated by PSI and followed 5-22 years (mean 10), GS was ≤6 in 1304 (65.8%), 7 in 466 (23.5%), 8 in 142 (7.2%) and 9-10 in 69 (3.5%). Men with positive bone or CT scans were excluded from implantation. 3 months of hormone therapy (NHT) was followed by Pd-103 implant to the prostate (dose 100 Gy) and 2 months later 45 Gy of conformal or image guided EBRT. NHT was given a median of 9 months. Within 2 months after treatment CT-based dosimetry was done with radiation doses converted to the biologic effective dose (BED). Biochemical freedom from failure (BFFF) was computed by the Phoenix definition, freedom from metastasis (FFM) in men with BF by absence of a positive bone or CT scan and cause-specific survival (CSS) by freedom from death in men with clinical recurrence. Association of risk features to GS 9-10 were compared by chi-square and linear regression (LR). Survival was computed by Kaplan-Meier estimates with comparisons by log rank and Cox hazard rates (HR).

Results

Mean age was 65.6 years (median 66, range 39-85); mean PSA was 9.4 ng/ml (median 6.7, range 0.3-300) and mean BED 194.6 Gy (median 200, range 15-299). Median BED for GS9-10 was 199 Gy2. BFFF, FFM and CSS by GS are shown in the table. The mean survival time for the 4 GS groups was: 1) 21.5 years (95%CI 21.2-21.8), 2) 19.2 years (95%CI 18.6-19.7), 3) 18.1 years (95%CI 17.2-19.1) and 4) 13.9 years (95%CI 13.1-14.8, p<0.001). Only clinical stage was associates with CSS with 15-year survival for ≤ T2a 100%, T2b-c 40.5% and T3 0% (p=0.025). Cox HR for CSS was significant for stage (p=0.055, HR 2.0) and BED (p=0.081, HR 0.985).

Conclusions

PBI combined with EBRT has excellent 15-year survival in men with GS 9-10 and clinical stage ≤ T2a. While 68% of men with T3 GS9-10 are alive at 10 years, at 15-year survival was 0. These men should be considered for alternate treatment strategies, possibly with early systemic therapy.

Funding

none

Introduction

We sought to identify variables that may predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT).

Methods

A retrospective analysis was performed on a prospectively maintained database of patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate or high-risk prostate cancer at a single institution between 1990-2011 with a minimum follow-up of 5 years. Patients were categorized as receiving no HT (n=438, 41.6%), ≤ 6 months (n=317, 31.1%) or > 6 months (n=298, 28.3%) of HT. Those receiving combination HT within one year of final testosterone (T) measurement were excluded, as well as patients receiving salvage ADT at any time. 5 and 10-year freedom from persistent hypogonadism (T<280 ng/dL) and castration (T<50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare risk of persistent hypogonadism and castration at a median follow-up of 6.5 years (post-treatment to final T) (IQR: 4.3-9.1 years; Range: 1.0-19.2 years).

Results

Of 1,981 patients receiving BT for clinically localized PCa, 1,053 met inclusion criteria. The 5-year freedom from hypogonadism rates were 92.4%, 88.9% and 87.0% for patients with no HT, ≤ 6 months and > 6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); 5-year freedom from castration rates were 99.2%, 98.0% and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%). In multivariable analyses, number of months of HT (continuous variable, HR=1.04, p=.030) and BT with EBRT vs. BT alone (HR=1.56, p=.010) significantly increased the risk of persistent hypogonadism. Older age (HR=1.04, p<.001) and diabetes (HR=1.43, p=.048) were also significant. Number of months of HT was the only variable which increased the risk of persistent castration (HR=1.09, p=.014).

Conclusions

EBRT is an independent risk factor for persistent hypogonadism among patients receiving BT for PCa. The mechanism of this finding needs to be elucidated, but may be secondary to scatter radiation during EBRT. Prolonged HT additionally increases the risk for persistent hypogonadism and castration.

Funding

none

Introduction

The exact role of pre-treatment (baseline) total serum testosterone (BST) is still controversial in patients with prostate cancer (PCa) and conflicting results are reported in the literature. We assessed the impact of BST on the risk of biochemical failure (BF) in patients with PCa and treated with definitive radiation therapy (RT).

Methods

The current study is a retrospective analysis of 360 prospective patients diagnosed with non-metastatic PCa between 2002 and 2014 and enrolled into seven different prospective multicentric phase II-III trials performed at our institution. All patients received definitive RT after initial diagnostic workup which included PSA and BST assessment. Patients were stratified according to hypogonadal (BST<11 nmol/L) vs. non-hypogonadal state (BST≥11 nmol/L). The ability of this BST cut-off to predict BF was assessed in Kaplan-Meier analyses, as well as in univariable and multivariable Cox regression analyses. Internal validation of our findings was performed using bootstrap resampling with 10,000 replications.

Results

The median (IQR) age at diagnosis was 71 years (65-74). Median (IQR) PSA was 7.7 ng/mL (5.6-12.1). Testosterone ranged from 0.7 to 28.9 nmol/L (mean: 11 nmol/L; median 10.2 nmol/L; IQR 8.3-13.0 nmol/L). The number of patients with BST < 11 nmol/L was 209 (58.0%), while a total of 151 patients had a BST ≥ 11 nmol/L (42.0%). A total of 272 patients (75.6%) had available BMI data, which ranged between 17.5 and 52.6, without significant differences between the two groups (p=0.1). ADT was administered only to 108 patients (30%), including all individuals diagnosed with PSA > 20 ng/mL. Median follow-up was 72 months. Overall, BF-free survival rates at 96 months was 79.6% (95% CI: 72.3-87.6%) in hypogonadal vs. 65.1% (95% CI: 55.3-76.7%) in non-hypogonadal individuals (p=0.042). In multivariable Cox regression analyses, BST < 11 nmol/L was associated with a significantly reduced risk of BF (HR: 0.50; CI 0.30-0.83; p = 0.007). After 10,000 bootstrap resamples, virtually the same results were recorded.

Conclusions

Oncologic outcomes for PCa after primary radiation therapy are affected by pre-treatment testosterone levels. Individuals with lower baseline testosterone levels experienced more favourable biochemical failure rates after adjusting for the use of ADT. As many still debate about the role of testosterone in PCa, our findings need to be validated in larger patient cohorts.

Funding

none

Introduction

Transrectal prostate brachytherapy is a common outpatient procedure for the treatment of clinically-localized prostate cancer. While the long-term morbidity and toxicities of prostate brachytherapy are widely published, rates of short-term complications are largely unknown. We aim to determine the incidence of acute hospital visits for treatment-related complications of outpatient prostate brachytherapy and to identify associated risk favors.

Methods

Patients who underwent prostate brachytherapy (CPT code 55875) for prostate cancer (ICD9 code 185) in an ambulatory surgery setting were identified in the Healthcare Cost and Utilization Project (HCUP) State Ambulatory Surgery Database for California between 2007-2011. Emergency department visits and inpatient admissions within 30 days of treatment were determined from the California HCUP State Emergency Department Database and State Inpatient Database, respectively. Risk factor analysis was performed using multivariate logistic regression.

Results

Over five years, 8,188 patients underwent brachytherapy for prostate cancer. Within thirty days, 576 (7.0%) patients experienced 686 hospital visits. Emergency department visits comprised the majority of the encounters (623 visits (79.8%), at a median time from surgery of 5 days (IQR 1-13). Inpatient hospitalizations occured on 158 visits (20.2%) at a median 11 (IQR 5-20) days from surgery. Common presenting diagnoses included urinary retention n=335 (42.9%), hematuria n=59 (7.6%), and urinary tract infection n=47 (6.0%)._x000D_ Logistic regression demonstrated that increasing patient age (65-75 years: OR 1.3 (95% CI 1.1-1.6); >75 years: OR 1.6 (95% CI 1.3-2.1)) and any inpatient admission within 90 days prior to surgery (OR 1.6 (95% CI 1.3-1.9) increased the risk of requiring hospital-based medical evaluation following outpatient brachytherapy. Baseline medical comorbidity (Charlson score) did not influence risk.

Conclusions

Emergency department visits and inpatient admissions are common following prostate brachytherapy, though at less frequent rates than previously reported. Risk of readmission is higher in elderly patients and those who have had recent inpatient hospitalizations.

Funding

None

Introduction

Urinary symptoms in men who are treated with prostate brachytherapy (PSI) are known to worsen over time. We explored which patient and treatment related factors were associated with increased IPSS score in men who presented with minimal symptoms prior to treatment.

Methods

Of 1981 men followed a minimum 5 years (mean 10, range 5-22), 1842 (93%) had pre-implant and last IPSS. 1110 (60.3%) had minimal initial urinary symptoms (score of 0-7). There were 491 (44.2%) low risk men treated with PSI alone or with 3-6 months of neoadjuvant hormone therapy (NHT) for prostate size > 50cc, 218 (19.6%) intermediate risk men treated with PSI plus NHT, or 76 (6.8%) with external beam irradiation (45 Gy EBRT) and 325 (29.4%) high risk treated by PSI/NHT/EBRT. NHT was given a median of 9 months. Median prostate volume (PV) was 37 cc (range 2.4-188.1). Data was prospectively collected on comorbidities. Radiation dose was converted to the biological effective dose (BED). Initial IPSS was compared to last by student-t test (2 tailed). Survival estimates for minimal symptoms increasing to moderate or severe (IPSS 8-19 and 20-35) were determined by Kaplan-Meier method with comparisons by log rank and Cox Hazard Rates (HR).

Results

The change from pre-treatment score to last IPSS score for the minimal, moderate and severe symptoms was: 3.6 to 7.3 (p<0.001), 11.6 to 11.3 (p=0.426) and 24.1 to 16.9 (p<0.001). For those with minimal symptoms the 10 and 15 year estimates for freedom from worse symptoms were 72.9 and 39.1%, respectively. The 10 and 15 year estimates for pre-treatment and treatment related factors for freedom from increased IPSS are shown in the table. Cox HR for the significant variables were age (1.02, p=0.024), implant type (p=0.019), BED (1.005, p=0.005) and HTN (0.766, p=0.019). Diabetes, heart disease, race, stroke, PV, and atrial fibrillation were not significant.

Conclusions

While most symptomatic men have improved scores, a substantial number of men with low IPSS experience worsening urinary symptoms with long-term follow up after PSI. Age, implant type, radiation dose and HTN are risk factors for an increase in IPSS.

Funding

none

Introduction

Numerous studies have examined urinary symptoms and incontinence risk in brachytherapy (BT) patients undergoing transurethral resection of the prostate (TURP), but there are limited data on quality of life (QOL) outcomes in this population. We aimed to evaluate the long-term impact of TURP and BT on QOL, in particular, as a function of pre-treatment symptom severity and timing of TURP in relation to implantation.

Methods

1848 patients underwent BT with or without external beam radiation therapy (EBRT) for the diagnosis of prostate cancer between October 1990 and May 2011 and were followed a minimum of 5 years. In total, 160 (8.7%) patients underwent TURP before or after implant for refractory urinary symptoms or retention. International Prostate Symptom Scores (I-PSS) and QOL bother scores were recorded prior to implantation and at follow-up evaluations. Patients were subdivided by timing of TURP - pre-implant (n=85), post-implant (n=69), pre- and post-implant (n=6) - and compared to patients not receiving TURP (n=1688). Paired t-test was used to analyze changes in QOL, stratified by pretreatment I-PSS. Chi-squared test and multivariate logistic regression were used to assess clinical and treatment-related factors predictive of worse long-term QOL.

Results

Median follow up after implantation was 9.0 years and median time to post-implant TURP was 20.0 months. Across all groups, men with mild pretreatment I-PSS had worsening urinary QOL (p<.001), while those with severe pretreatment I-PSS improved (p=.005). This was also true for men who never had a TURP (p<.001 for mild, p<.001 for severe). Men with moderate symptoms undergoing TURP had no significant QOL change (p=.89). In men with pretreatment QOL score < 2, age over 65 years was the only predictor of poor QOL (score ≥ 3) at last follow up; EBRT, hormone therapy, and BED > 200 Gy had no influence on reported QOL in these men.

Conclusions

Most BT patients regressed toward the mean over time with respect to urinary QOL, irrespective of receipt or timing of TURP. Men with worse urinary QOL who underwent a post-implant TURP improved while men with a mild QOL bother score were worse after TURP. These data suggest a more conservative approach should be considered when electing a post-implant TURP unless patients have significant bother.

Funding

None

Introduction

Limited data is available on the influence of race on long-term potency preservation after prostate seed implant brachytherapy (PSI). We sought to identify if race and comorbidities effect long-term erectile function (EF) following PSI.

Methods

1,909 patients were identified from a prospectively managed database who underwent PSI for T1-T3 localized prostate cancer from 1990 to 2011. Median follow up time was 9.2 years (range 5-22). Patients were stratified by race and treatment type (PSI alone, PSI + EBRT, PSI + neoadjuvant hormone therapy (NHT) or PSI + EBRT and NHT. EF was assessed by SHIM questionnaire grouped into 4 categories (A: 0-7, B: 8-11. C:12-16 and D: 17-25) where C and D were considered potent. EF was recorded at initial, 5 year and last visit. NHT was given a median of 6 months. Last testosterone (T) levels were recorded a median 6 years after PSI. Pre- and post-treatment variables were compared by ANOVA, chi-square and multivariable regression. Potency preservation was estimated by Kaplan-Meier method with comparisons by log rank and Cox hazard rates (HR).

Results

There was no difference in SHIM scores between races pre-treatment. Caucasians (CC) were older than African Americans (AA) and Hispanics (H) (p=0.002). 42.6% of CC received implant alone compared to 32.5% of AA, and 28.9% of H (p<0.001). Combination therapy was more common in AA (40.8%) and H (41.3%) compared to 25.9% for CC (p<0.001). NHT was given to 59.8% of CC, 62.6% of AA and 61.2% of H men (p=0.001). EF was preserved overall in 82.5% and 40% at 5 and 10 years. Cox HR for EF included pre-SHIM score (HR 1.69, p<0.001), age (HR 1.04, p<0.001) and NHT use (HR 1.05, p=0.011). Total radiation dose, type of implant, race, T level and HD, diabetes, hypertension were not significant.

Conclusions

The presence of HD, pretreatment EF, age and prolonged use of NHT negatively impact EF. Other comorbidities and race do not appear to influence long-term preservation of potency.

Funding

none

Introduction

Treatment options for localized prostate cancer include radical prostatectomy (RP) and radiation therapy (RT). Treatment choice depends on patient age, comorbidity and preferences as well as tumor characteristics. . Initial treatment decisions can have long-term consequences that can result in complications, possible future secondary treatments and significant economic impact. We sought to compare 5-year annual treatment-related complication (TRC) costs for patients treated with RP or RT for localized prostate cancer._x000D_

Methods

We performed a population-based retrospective cohort study of all men ?18 years old who underwent RP or RT (external beam or brachytherapy) for clinically localized prostate cancer in Ontario, Canada from 2002 to 2009. Costs were determined using a validated costing algorithm using linked administrative databases, to capture inpatient hospital admissions, emergency department visits, cancer clinic visits, physician billings and Ontario Drug Benefit Plan medication usage for 5 years after treatment (including costs for initial treatment). Costs for medical care unrelated to management of prostate cancer or its treatment-related complications were excluded. Costs were adjusted for inflation to 2015 Canadian dollars. We matched men treated with RP and RT 1:1 using a propensity-score including age, income quintile, co-morbidity score and year of diagnosis. Negative binomial regression was used to assess the association between treatment modality and costs.

Results

In total, 28,849 men underwent treatment for localized prostate cancer from 2002 – 2009 in Ontario. Men who underwent RT (n=12,675) were older, from less affluent neighborhoods and had more comorbidities than men who underwent RP (n=16,174, p<0.001). Men who underwent RT had higher total 5-year per patient treatment-related costs than men who underwent RP ($16,716/pt vs. $13,213/pt), with a mean incremental difference of $3,503/pt._x000D_ Men who underwent RT had a lower relative cost in their first year after treatment, compared to those receiving RP (RR 0.97, 95% CI 0.94 – 1.0, p=0.025). There was no difference in relative cost in year two (p=0.1). In years 3, 4 and 5, RT had a significantly higher relative cost than RP (p<0.05 for all). _x000D_

Conclusions

Men who undergo RT have significantly higher 5-year total treatment-related costs compared to men who undergo RP. Relative costs are higher in the first year for patients treated with RP and increasingly higher in subsequent years for patients treated with RT.

Funding

Ajmera Family Chair in Urologic Oncology

Introduction

External beam radiation therapy is a common modality for prostate cancer, although acute and chronic side effects remain significant. Radiofrequency tracking beacons allow for real-time tracking of the prostate using 3 non-coplanar markers and intrafraction monitoring of prostate position and is one modality of image guidance that may help to decrease local radiation exposure._x000D_ _x000D_ This study retrospectively evaluated the acute and chronic morbidities of radiofrequency tracking beacons vs CBCT radiotherapy.

Methods

This is a IRB-approved single center retrospective review of patients who presented to St. Elizabeth Hospital for radiofrequency tracking beacons or CBCT for prostate cancer during April 2010 - December 2011. Inclusion criteria were T1/T2 prostate cancer without prior radiation, prostatectomy, or brachytherapy. A total of 191 patient charts were reviewed and 131 patients were included: 55 cone-beam and 76 beacons transponders. Short-term and long-term morbidites were recorded: short-term were defined as under two years and long-term was defined as lasting or beginning greater than two years after treatment. These toxicities were graded using the Radiation Therapy Oncology Group (RTOG) toxicity grading system. Significance was set as p<0.05 and analyzed using single variate analysis.

Results

There were no significant differences between age, Gleason score, starting PSA, and use of anti-androgens between the treatment_x000D_ groups. The short term morbidities of CBCT vs radiofrequency tracking beacons were_x000D_ significantly different (p<0.01) at 27.3% and 59.2%, respectively._x000D_ Nocturia (p<0.01) and hematuria (p=0.05) were significantly higher in the radiofrequency beacons. Long-term morbidities of CBCT vs tracking beacons were_x000D_ not significant (p=0.59) with values of 5.5% vs 7.9%. There were no_x000D_ significant differences in biochemical cancer recurrence._x000D_

Conclusions

For short-term morbidities, beacons transponders patients experienced side effects significantly more than CBCT patients, particularly those of nocturia and hematuria._x000D_ This may be due to irritation from beacon placement and increased radiation dosage when using beacons transponders._x000D_ _x000D_ The long-term morbidities correlate with current literature as there were no significant differences in biochemical cancer recurrence and long-term morbidities between standardly used radiation modalities. This study suggests that beacons transponders do not decrease the amount of radiation associated short-term morbidities._x000D_

Funding

None

Introduction

The prognostic heterogeneity in patients with Gleason Score (GS) 7 prostate cancer (PC) is owed to the more aggressive behavior of GS 4+3 vs. 3+4 disease. Modifications in the Gleason grading system were proposed to address these differences in cancer behaviors when reporting GS 7 PC, as Grade Group 3 portends a higher likelihood of systemic spread compared to Grade Group 2. Prognostic differences are recognized in patients undergoing surgical extirpation; we therefore sought to investigate differences in outcomes between Groups 2 and 3 patients treated with radiotherapy with or without hormone therapy (HT).

Methods

A retrospective analysis was performed on a prospectively maintained database of patients receiving brachytherapy ± external beam radiation therapy ± hormone therapy (HT) for NCCN low, intermediate or high-risk PC at a single institution between 1990-2011. Patients with a minimum follow-up of 5 years were included. Kaplan-Meier survival analyses were used to compare GS 3+4 vs 4+3 for the study endpoints of biochemical recurrence (BCR; Phoenix criteria), distant metastases, and cancer specific survival (CSS), with and without stratification by biological effective dose (BED; <150 vs. 150-200 vs. >200 Gy). Cox proportional hazards model was used to assess risk of BCR over time, adjusting for HT receipt, GS, stage, PSA, and BED.

Results

472 patients were identified with GS 7 PC; 276 with GS 3+4 and 196 patients with GS 4+3. No significant differences were seen in BCR (p=0.349), distant metastasis (p=0.07), and CSS (p=0.62) in GS 3+4 vs. 4+3. Among patients with PSA > 10 ng/ml or stage > T2b, significant differences in biochemical freedom from failure (BFFF) were observed for GS 3+4 vs. 4+3 stratified by escalating BED (table 1). Neoadjuvant HT improved 10-year BFFF from 81.3% to 88.2% for GS 3+4 and from 66.3% to 87.6% for GS 4+3 (p=0.021). Cox proportional hazards model demonstrated HT receipt (HR 11.86, 95% CI 1.26 – 112.06, p=0.031) and total BED (HR 0.98, 95% CI 0.97 – 0.99, p=0.001) significantly impact time to BCR.

Conclusions

BCR, distant metastasis, and CSS were similar between patients in Group 2 and 3 PC treated with radiotherapy. Higher BED substantially improves BFFF in higher risk patients with PSA >10 and stage > T2b, especially in Group 3. Higher dose and neoadjuvant HT should be strongly considered in GS 7 PC with adverse features.

Funding

None

Introduction

Long-term complications of diabetes include cardiovascular disease, retinopathy, nephropathy, and neuropathy. Diabetic patients with prostate cancer could be at a high risk of radiation-induced proctitis following radical radiotherapy. Our aims were to determine whether diabetic patients treated by radical radiotherapy for prostate cancer have higher incidence, severity, and duration of radiation proctitis.

Methods

716 patients with prostate cancer were recruited. Patients were stratified into diabetic patients and non-diabetic patients. The incidence, severity, and duration of proctitis were the main outcomes. A polynomial ordered logistic regression was fitted to determine the influence of diabetes status, age, blood pressures medication, co-morbidities, Gleason score, PSA after treatment, and tumour stage on the grades of proctitis. Time to resolution per year was modelled as a negative binomial generalised linear model.

Results

Data exploratory analysis suggested that the only highly significant explanatory variable was the presence or absence of diabetes. Polynomial ordered logistic regression, however, showed that the presence (or not) of diabetes remained as the only significant predictor (t = -2.74; p = 0.0059) of severity of proctitis (Figure 1). A negative binomial generalised linear model showed that both grade of proctitis (z = -17.178; p < 0.001), and diabetes (z = -5.92; p < 0.001), were highly significant predictors of time to resolution.

Conclusions

Diabetic patients were significantly more likely to have proctitis after radical radiation therapy for prostate cancer. Diabetes was significantly associated with an induced risk of radiation induced proctitis and also with deceleration of its resolution.

Funding

Prostate Cancer UK.

Introduction

Prostate brachytherapy is an effective option for the treatment of low-to-intermediate risk localized prostate cancer (CaP). Post-implant dosimetry, based on computerized tomography (CT) or magnetic resonance imaging (MRI), remains an important part of brachytherapy treatment protocols to ensure adequate prostate dosing. New techniques, including the use of strands of radionuclide seeds, have been developed in recent years with the goal of improving delivery of radiation to the prostate while maintaining efficacy and minimizing radiation to surrounding structures. In this study, we evaluate the impact of transitioning from loose seeds to stranded seeds based on dosimetry delivered to the prostate and rectal wall and post-implant PSA values._x000D_

Methods

We retrospectively reviewed the charts of 225 patients who underwent Palladium-103 prostate brachytherapy seed implant for low-to-intermediate risk prostate cancer January 2003-August 2013. 91 patients underwent implantation of loose seeds (LS) between January 2003 and June 2006 and 134 patients underwent placement of stranded seeds (SS) between June 2007 and August 2013. Pre-treatment variables including gland volume, Gleason score and prostate-specific antigen (PSA) were similar between the two cohorts with the exception of age. Post-implant dosimetry quality and critical organ dosimetry were assessed by determining the minimal dose received by 90% of the prostate gland (D90), the dose covering 50% of the rectal wall (D50) and the percent volume of the prostate with a dose 200% of the prescription (V200). These values were then compared between the LS and SS cohorts. PSA levels were recorded approximately 3 months and 12 months after implantation._x000D_

Results

The D90 and the mean D90 as a percentage of the prescribed dose were unchanged after transitioning to SS. The decrease in rectal wall D50 after transitioning from LS to SS was statistically significant (p<0.005). Similarly, the V200 decline from 28.1 cm ³ to 16.8 cm³ after changing to SS was also statistically significant (p<0.005). Mean PSA at 3 months after seed implantation was 1.10 ng/mL for the LS group and 1.34 ng/mL for the SS group. At one year, mean PSA was 0.60 ng/mL for the LS group and 0.69 ng/mL for the SS group. There was no statistically significant difference between the two groups in terms of post-implant PSA values.

Conclusions

In our patient cohort, the shift from loose to stranded seeds resulted in the same radiation dose to the prostate with no significant difference in post-treatment PSA while decreasing unnecessary radiation to surrounding organs._x000D_

Funding

none

Introduction

Fiducial marker placement is required in patients undergoing robotic-based Stereotactic Body Radiotherapy (SBRT) for prostate cancer in order to track the six degrees of prostate motion that occur intrafractionally, during treatment. Many patients take anti-coagulant medication due to other comorbidities. Anticoagulation therapy can cause patients to bleed during procedures and, in general practice, are often temporarily discontinued prior to invasive medical procedures to reduce that risk. Some patients may not be able to temporarily discontinue anticoagulation therapy due to an increased risk of a thromboembolic event from their comorbid medical conditions_x000D_ _x000D_ _x000D_

Methods

From August 2015-October 2016 23 consecutive patients on chronic anticoagulation therapy who were not cleared to stop these medications underwent TRUS-guided fiducial marker placement for SBRT/Image Guided Radiation Therapy. The reasons for patients being on anticoagulation therapy were recent stent placement (11,) myocardial infarction (7,)atrial fibrillation (3,) and pulmonary embolus (2.)The anticoagulation consisted of Plavix (9,)Aspirin (7,)Coumadin (3,)Lovenox (2,)Eliquis (1,)Brillinta (1,)Pradaxa (1,)and Effient (1,) All patients received 4 fiducial markers placed under Transrectal ultrasound guidance (TRUS.) EMLA Cream and lidocaine gel were used to numb the perineum and rectum. 2 needles each double loaded with 2 gold fiducial markers with a spacer in between were placed transperineally into the prostate. 2 fiducial markers were placed at the right and left base and 2 fiducial markers were placed at the right and left apex. Patients had a CT scan after procedure to confirm ideal geometry of the marker placement. The needles were withdrawn as was the ultrasound transducer. Gentle pressure was applied by the nursing staff. All patients were monitored for bleeding afterwards by a registered nurse_x000D_ _x000D_ _x000D_

Results

All 23 patients who were on anticoagulation and underwent fiducial marker placement were discharged home the same day of the procedure. No patient experienced significant bleeding in the peri-procedural window and no patient had any untoward cardiovascular event._x000D_

Conclusions

This series suggests active anticoagulation is not an absolute contraindication to fiducial marker placement _x000D_ in patients undergoing SBRT or IGRT for prostate cancer._x000D_ Transperineal fiducial marker placement appears to be safe in patients on active anticoagulation medication. These patients should be closely monitored after the procedure for bleeding complications._x000D_

Funding

None

Introduction

Radical prostatectomy (RP), intensity modulated radiation therapy (IMRT) and brachytherapy (BT) are three major definitive treatment modalities for localized prostate cancer in recent years. While a lot of technical progress are seen in this decade, patients with localized prostate cancer are often struggling with making a decision of their treatment. It might be due to luck of information in terms of comparing the outcomes among these modalities since only few reports are seen in the literature. _x000D_ We analyzed the results of three treatment modalities using propensity score in a single institution in Japan._x000D_

Methods

From Jan 2004 to Dec 2015, a group of 2272 patients with clinically localized prostate cancer treated with RP (570pts), IMRT (391pts) and BT(1311pts) were identified in our institution. The records of RP(n=410) , IMRT(n=276) and BT(n=1034) patients with a minimum of 2 years of follow-up (total 1720) were reviewed. Propensity scores were calculated using multivariable logistic regression based on the covariates including patient's age, preoperative PSA, Gleason score, number of positive cores, clinical T stage. Each cohort were categorized according to NCCN risk classification and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as RP: PSA >0.2ng/ml, IMRT, BT: nadir PSA level +2ng/ml.

Results

Median follow-up was 75 months (mo) for RP, 57 mo for IMRT and 64 mo for BT patients. After adjustment of propensity scores, a total of 300 patients (150 each) and 468 patients (234 each) were matched for RP vs IMRT cohort and RP vs BT cohort, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival in these two cohorts (RP vs IMRT:p=0.421, RP vs BT:p=0.764). Regarding biochemical failure free survival, there was statistically significant differences in all risk group in RP vs IMRT cohort (High-risk: p=0.000, Intermediate-risk: p=0.001, Low-risk: p=0.007), while significant differences were observed in low (p=0.003), intermediate (p=0.006) risk group among RP vs BT cohort.

Conclusions

Our mid-term outcomes for localized prostate cancer using propensity score analysis demonstrated no significant differences in overall survival. Despite the difference of biochemical failure definition, IMRT and BT improved biochemical failure free survival compared to RP with excellent tumor control.

Funding

None

Introduction

Studies have shown that adjuvant radiation therapy (ART) decreases biochemical recurrence after radical prostatectomy in men with adverse features. Guidelines recommend including these patients in a shared decision making (SDM) discussion about the risk and benefits of ART. Despite possible benefits, ART is not commonly prescribed. Our objective is to understand the relationship between adverse features and referral to Radiation Oncology (RO) in high-risk patients who had a SDM discussion with their urologist.

Methods

Pathologic data was prospectively collected at a single site on all radical prostatectomy specimens from 2009-2015. Patients with adverse features were selected, defined as positive surgical margins (SM), extraprostatic extension (EPE), and seminal vesicle invasion (SVI). All patients had a negative 3-month postoperative PSA. Chart review recorded ART discussion in the notes, explicit recommendation for ART, referral to RO for ART, receipt of ART, and if a patient was referred for salvage therapy. Univariable logistic regression analysis for each individual adverse feature was performed, and a second analysis for patients with 2 or more features.

Results

200 patients had any adverse feature. ART was discussed in 131 (66%) and recommended to 46 (23%). Thirty-nine patients (19.5%) had a consultation with RO for ART, 24 (12%) underwent ART, and 30 (15%) were referred for salvage therapy. The likelihood of recommendation for ART was 6.7%, 14.3%, 20%, and 52% for SM, EPE, SVI, and 2 or more risk factors, respectively. Odds ratios are presented in Table 1.

Conclusions

To our knowledge, this is the first study to examine how adverse features influence referral for ART after a SDM discussion after prostatectomy. In our study, ART was discussed with the majority of patients but an explicit recommendation was underutilized. A single individual adverse feature negatively correlated to recommendation, whereas multiple adverse features were strongly associated with referral.

Funding

none

Introduction

In 2014, approximately 6,100 people in the United States underwent living donor nephrectomy. Unlike other types of organ donation, this patient population has a longer-than-average life expectancy due to strict selection criteria. Greater than 99% of patients that donated a kidney at Cedars-Sinai Medical Center donated to an immediate family member, relative, or close friend. Our study seeks to qualify and quantify functional changes in the relationship between the donor and the recipient before and after surgery as well as to identify perioperative complications and stress to determine if patients are content with their decision to donate.

Methods

From 2002-2012, 532 patients underwent donor nephrectomy for kidney transplant at Cedars-Sinai Medical Center. After IRB approval, a randomized subset of these patients were administered a standardized questionnaire regarding his or her experience. We assessed if each patient would undergo the donation process again, now having more intimate knowledge and appreciation of the pre- and post-operative surgical and medical course.

Results

Of the fifty patients who participated in our survey, 92% stated that their relationship with the recipient improved after surgery. Of the 8% that noted a deterioration in the relationship, there was a distribution of dissatisfaction with relation to the sexual relationship (n=1), recipient personality changes (n=1), or divorce (n=2). Approximately 10% of patients experienced a complication related to surgery, all of which were clavian grade I-II. Examples of these included incisional hernia (n=3, upper midline incision, BMI>30 kg/m2) and urinary tract infection (n=2). Overall, 98% of patients were extremely satisfied with the donation process and would not hesitate to participate again. Only one patient stated that he would not donate again, as he developed an unanticipated glomerulonephropathy not related to surgery that required hemodialysis.

Conclusions

Our research demonstrates that the act of donating a kidney overwhelmingly enhances the bond between the donor and recipient. Even donors who noted a decline in their relationship with the recipient all stated that they would still donate if faced with the same decision again. This suggests that the relationship with the recipient is of highest importance and a crucial component of pre-operative counseling that should be emphasized. Our urology group has started to incorporate this practice in our management with great success.

Funding

None

Introduction

ABMR is a diagnostic challenge in living donor kidney transplant (LKTx) medicine, and there is a need to identify predictive markers of ABMR to improve graft survival. The use of serum N-glycans as a predictive biomarker of ABMR has not yet been tested. In the present study, we performed serum N-glycomics in transplant patients and evaluated its potential as a predictive serum-based biomarker of early ABMR.

Methods

N-glycomics in whole serum and immunoglobulins (Igs) fraction were performed in randomly selected 16 recipients with biopsy-proven ABMR occurred within 1 month after LKTx, 40 recipients with biopsy-proven TCMR, and 141 recipients without any adverse events. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis.

Results

Serum sialyl hybrid-type N-glycans (m/z 1709, 1871, and 2033) levels before LKTx and on postoperative Day 1 (POD1) was significantly lower in recipients who developed ABMR than non-ABMR group. The m/z 2033 N-glycan <1.3 μM and the presence of preformed donor-specific antibodies (DSA) on POD1 were found to yield a higher odds ratio for prediction of ABMR than did other factors according to logistic regression analysis. Receiver-operating characteristic area under the curve for m/z 2033 < 1.3 μM combined with preformed-DSA status was 0.86. Combined preformed DSA with m/z 2033 N-glycan status; thus, double-positive patients (preformed-DSA positive and m/z 2033 < 1.3 μM) or single-positive patients (preformed-DSA positive or negative and m/z 2033 > 1.3 μM or < 1.3 μM) can cover all 16 ABMR cases. These results suggest that the combined indicator holds promise for identification of patients who will not develop ABMR by means of serum samples collected on POD1. Although, N-glycan profile of immunoglobulin (Ig)s fractions compared with those of whole-serum, ABMR-related N-glycans in Igs fractions were not detected. Therefore, the ABMR-related N-glycans carrying proteins are not an Igs.

Conclusions

The serum m/z 2033 sialyl hybrid-type N-glycan combined with preformed DSA status may predict acute ABMR in patients undergoing LKTx. _x000D_

Funding

This work was supported by JSPS KAKENHI grant number 15K15579 and grant number 25220206. This work was also supported by Japanese Society for Clinical Renal Transplant for an incentive scheme of clinical research grant 2014.

Introduction

Despite improvements in medical care, surgical removal of failed transplant renal allografts may be mandated by sepsis, bleeding, pain, or erythropoietin resistance. Transplant nephrectomy has historically been performed in an open fashion by transplant surgeons and carries morbidity up to 50% with mortality up to 7%. To date, there is a single reported case of robot assisted transplant allograft nephrectomy from a deceased donor kidney. We herein present our series of robotic assisted transplant nephrectomy (RTN).

Methods

All patients who underwent robotic allograft nephrectomy at Mayo Clinic Arizona were included. Patients were not excluded for undergoing a concurrent procedure. All RTN were performed by a single Urologist (EPC) in conjunction with a single Transplant surgeon (NNK) via a transperitoneal approach utilizing a dual console Da Vinci Robotic Si/Xi surgical system. Study design was retrospective and observational. Variables analyzed included: demographics (age, BMI, ASA), comorbidities, transplant related (time from transplant to transplant nephrectomy, living related or deceased donor transplants), operative variables (operative time, estimated blood loss and additional procedures performed) peri-operative variables (length of stay (LOS), drain duration, Foley catheter duration, and hemoglobin change), and 30-day Clavien-Dindo complications. All variables were analyzed by non-parametric tests with commercially available software (SPSS vs, 21, Chicago, Illinois

Results

Six patients underwent RTN between 10/31/2014 until 4/31/2016. The time from transplant to transplant nephrectomy was a median of 5.9 years (range: 0.3 - 40). The majority of transplants were from deceased donors (66%). The median operating time was 306 minutes (range: 178 – 532). Of note, in two of the six RTN cases bilateral laparoscopic native nephrectomies were performed and in a third case a robotic nephrectomy and a lymph node biopsy by plastic surgery was performed. There were no intraoperative complications or conversions to open nephrectomy. Estimated median blood loss was 150 mL (range: 100 – 400), with a transfusion rate of 16%. Drains were utilized in 84% of patients and for a median of 2 days. There were three minor complications.

Conclusions

In this first reported series of robotic transabdominal allograft nephrectomy we demonstrate the safety and feasibility of the use of robotic technology for transplant nephrectomy. This is a small series that includes our learning curve.

Funding

None

Introduction

Hepatitis C Virus (HCV) infection affects more than 200 million people worldwide. The infection rate of HCV reaches approximately 1.8% to 8% in kidney transplant (KTx) recipients, which is much higher than that of normal people because of the repeated blood transfusion, dialysis, and immunosuppression. In current work, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and tolerability of sofosbuvir (SOF)-based Direct-Acting Antiviral Agents (DAAs) in KTx recipients.

Methods

A systematic literature search of MEDLINE, EMBASE, The Cochrane Library, Web of Science, and ClinicalTrials.gov was performed to identify clinical trials evaluating SOF-based DAAs in KTx with HCV infection published or in press from 2012 to present. Effect sizes were collected as pooled event rates (sustained viral response, SVR12 or SVR4) with corresponding 95% CIs. All statistical analyses were conducted by R 3.3.1.

Results

Eleven studies with a total of 360 KTx recipients were finally included. Most KTx recipients (88.1%) had HCV-1 infection. A total of 24 patients who received dual or combined organs transplants were reported. The overall rate of SVR12 reached 94% (95%CI: 88% to 97%). No significant heterogeneity was observed (p=0.92). SVR4 reached 99% (95%CI: 93% to 100%). The clearance rate of HCV RNA at the end of treatment (EOT) (12 weeks) was 94% (95%CI: 87% to 97%). The rate of rapid virological response (RVR) was 73% (95%CI: 55% to 85%; I2=58.9%, P=0.045). The SOF-based DAAs did not impact the kidney function, whereas the liver enzyme parameters (such as ALT, ATS) had decreased during. The most frequent AEs were headache 6.9% (n=25/360), asthenia 4.4% (n=15/360), and fatigue 3.3% (n=12/360).

Conclusions

In summary, our meta-analysis represented the first systematic review to evaluate the efficacy and safety of SOF-based DAAs in the post-KTx setting for a total of 360 patients from eleven individual studies. Data from current analysis suggest that SOF-based DAAs therapy is a highly effective treatment with an SVR12 rate (94%) and excellent tolerability, compared to prior interferon therapy for KTx recipients.

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81200551, 81300627, 81200551 and 81470980), the Prostate Cancer Foundation Young Investigator Award 2013 and Foundation of Science & Technology Department of Sichuan Province (Grant No. 2013SZ0006 and 2015SZ0230).

Introduction

Evaluating learning curve of a new procedure is important in order to assess the reproducibility and ease of adoption of the procedure, and also to track progress of an institution adopting the new procedure. This study reports the results and learning curves of robotic kidney transplantation (RKT) with regional hypothermia at a center that recently adopted this procedure._x000D_

Methods

33 patients underwent Vattikuti Urology Institute technique of RKT in Turkey, by surgeons routinely performing robotic surgery and kidney transplantation. Standard KT outcomes were noted with a minimum follow-up of 1 month for all, and compared to the results of an established RKT program in India, who used the same technique of RKT. CUSUM analysis was done to evaluate the learning process. Target values were based on the average values of the established RKT program. Completion of learning curve was defined as anastomosis and rewarming times plateauing within 2 standard deviations (SD) of the target value.

Results

All patients underwent RKT successfully. The mean console, warm ischemia, and rewarming times were 187±34.6 min, 1.89±0.5 min, and 58.0±17.8 min respectively. Arterial, venous, and ureterovesical anastomosis times were 19.3±5.9, 21.9±6.8, and 22.5±4.2 min respectively. The median hospital stay was 10 days (6-14 d), and creatinine at discharge was 1.43±5.73 mg/dl. These results differ significantly from the results of the established program with regard to anastomosis times and rewarming time (p<0.05 for all). However, there was no difference in creatinine at discharge (p>0.05) (figure 1a). There was no delayed graft function, no Clavien grade ?3 complications, lymphoceles, vascular or ureteral complications; one wound infection requiring medical management. CUSUM analysis revealed that learning curve lasted for 9 cases with regards to rewarming time, 19 cases for arterial anastomosis, 18 cases for venous anastomosis. No learning curve existed for uretrovesical anastomosis (Figure 1b).

Conclusions

RKT has excellent outcomes, and low complication rates at a center that recently adopted this procedure. It has a short learning curve, and is reproducible. The longer anastomosis times at the start of learning curve do not affect graft function, supporting the hypothesis that regional hypothermia is protective._x000D_

Funding

none

Introduction

Recently, desensitization therapy became more widely used in ABO incompatible kidney transplantation (ABOi-KTx). A body of evidence has been accumulated suggesting that anti-A, anti-B antibody titer is not necessarily a good indicator for the development of acute antibody mediated rejection (AMR) or for favorable or unfavorable patient outcome. We have omitted the pre-transplant antibody removal in selected patients since 2010 at out institution.

Methods

Twenty-two patients with baseline antibody titer ≤ 1:64 received ABOi-KTx without pre-transplant antibody removal between 2010 and 2015 (Group 1). Historical control group consisted of 22 patients with baseline antibody titer ≤ 1:64 who received ABOi-KTx with 2 or 3 sessions of pre-transplant antibody removal before 2009 (Group 2). All patients were treated with calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and methylprednisolone (MP) starting 4 weeks before ABOi-KTx. Two doses of rituximab (100mg) were given in both groups before ABOi-KTx. Protocol biopsies were performed 1-2 month after ABOi-KTx.

Results

Recipient and donor age, sex, the number of HLA mismatch were not significantly different between the 2 groups. Baseline antibody titers (IgG) were 1:17 (range 0-64) and 1:18 (range 0-64) in Group 1 and 2, respectively (P=0.81). Antibody titers at the day of ABOi-KTx were 1:10 (range 0-32) and 1:8 (range 0-32) in Group 1 and 2, respectively (P=0.43). Five year graft survival were 100 % in both groups. Serum creatinine levels at 3 years after ABOi-KTx were 1.25±0.75 and 1.46±0.43 mg/dl in Group 1 and 2, respectively (P=0.39). Biopsy proven AMR occurred in 2 patients of Group 1 (9.1%) and 3 patients of Group 2 (13.6%). AMR in these patients was abrogated with steroid pulse therapy with or without plasma exchange. There was no significant difference in protocol biopsy results of Banff 2013 criteria between the 2 groups. C4d score more than 2 was detected in 72 % in Group 1 and 75 % in Group 2 (P=0.97). IgM deposition on peritubular capillary was seen in 38.8 % in Group 1 and 60.0 % in Group 2 (P=0.25).

Conclusions

Pre-transplant antibody removal is not required for patients whose serum antibody titers are ≤ 1:64 in ABOi-KTx as long as desensitization therapy consisting of CNI, MMF, MP and retuximab is implemented appropriately.

Funding

none

Introduction

The elderly represent a rapidly growing population among kidney transplant recipients, however, this population remains underrepresented in clinical trials. Moreover, age-specific effects of immunosuppressive therapies in renal transplantation remain poorly understood.

Methods

Here, we assessed the impact of Rapamycin on alloalloimmune responses in aging using a fully MHC-mismatched (DBA/2 on B57BL/6) murine transplantation model.

Results

Old untreated recipients displayed prolonged skin graft survival compared to their young counterparts (median survival time 9 vs. 7 days, p=0.006). Surprisingly, treatment with Rapamycin led to a marked prolongation of graft survival specifically in old recipients (19 days vs. 12 days, p=0.004). This age-specific effect was not linked to changes in frequencies or subset composition of CD8⁺ and CD4⁺ T cells. Furthermore, anti-proliferative effects of Rapamycin on CD8⁺ and CD4⁺ T cells as assessed by in-vivo BrdU-incorporation were comparable in both young and old recipients. In contrast, systemic production of IL-10 was markedly elevated in old recipients treated with Rapamycin. This in-vivo shift in cytokine balance was linked to an emergence of IFN-γ/IL-10 double-positive regulatory type 1 cells during Th1-differentiation of old T helper cells in presence of Rapamycin, a process independent of regulatory T cells.

Conclusions

Our results demonstrate a novel pathway of age-dependent alloimmunity with relevance for renal transplantation.

Funding

S.G.T. was supported by grants from the National Institutes of Health (RO1AG039449). K.M. was supported by Osaka Medical College Educational Foundation. M.Q. (QU 420/1-1) and T.H. (HE 7457/1-1) were supported by the German Research Foundation (DFG).

Introduction

As the waiting time increases for listed renal failure patients, it is becoming common to encounter patients with minimal or no urine output with small shrunken bladders at the time of transplant. Mirabegron has proven benefit in treating overactive bladder(OAB) symptoms by relaxing the bladder through beta-3-adrenergic receptors. Our aim is to evaluate the efficacy of Mirabegron following kidney transplantation on patients with small bladder capacity.

Methods

Kidney transplant recipients with small bladder volumes who experienced OAB symptoms and were started on Mirabegron therapy within 3 months after transplant were included in this study. Patients were excluded if they had evidence of urinary tract infection or a history of complex urologic surgeries preceding transplantation. We used the OAB-symptom score (OAB-SS; Journal of Urology, 2007), a simple self-report questionnaire evaluating OAB symptoms. The minimum OAB-SS score for inclusion was 12. Patient demographics and OAB-SS pre and post-Mirabegron were collected and compared using paired t-test analysis.

Results

The 36 participants were predominantly male (83%) and deceased-donor kidney transplant recipients (86%). Median age was 48 years (IQR 36.5-60). 47% of patients reported pre-transplant urinary symptoms, most commonly recurrent UTI (28%). BPH-lower urinary tract symptoms (LUTS) reported by 30% of males may contribute to the sample sex imbalance. Before Mirabegron initiation, 44% of patients had failed trials of at least one pharmacologic agent and over 20% had failed trials of at least two medications. After starting Mirabegron therapy, 86% reported a decrease in OAB-SS. Overall mean score change was -4.7 points (p<0.001). Mean score on each OAB-SS survey question also decreased significantly (p<0.001, Table 2).

Conclusions

Mirabegron effectively reduces severity of symptoms related to small bladder volume following renal transplantation by increasing bladder relaxation and storage capacity.

Funding

none

Introduction

The renoprotective effect of sildenafil has been proven in animal model. Also, it is reported to enhance expression of hepatocyte proliferating antigen after hepatic ischemia/ reperfusion injury (IR) in animal model. Yet this was not studied before in renal IR. We aim to investigate the role of local sildenafil administration in enhancement of renal recoverability and regenerative capacity after renal IR in canine model.

Methods

Seventy two male mongrel dogs were classified into 3 groups (each consists of 24 dogs): sham (right nephrectomy without left renal ischemia), local (LC) group (right nephrectomy, left renal ischemia for 6o minutes and local perfusion of ischemic kidney with saline and heparin for 5min immediately after ischemic induction) and local Sildenafil (LS) group (as LC and local perfusion with sildenafil 0.5 mg/kg). Each group is subdivided into 4 subgroups (6dogs each) according to time of scarification (1, 3, 7 and 14 days). Serum creatinine (Scr) and diuretic renography were performed for all dogs at the day of sacrification and compared with pre-ischemic values. Histopathological examination of the kidney was performed by un-informed pathologist. Renal cortex and medulla were examined for necrosis, interstitial fibrosis and regenerative indices (RI). Regenerative indices (RI) are mitosis, solid tubules, solid sheet, hyperchromatosis and prominent nucleoli. Also, immunohistochemical examination of renal tissue was done for assay of proliferative marker ki-67.

Results

Renal function tests were statistically significant lower in ischemic groups (LC and LS) in comparison to sham through the study period, where LS group showed statistically significant lower serum creatinine and higher GFR at all end point times than LC group. (Figure 1) Sildenafil-treated group showed statistically significant lower renal cortical and medullary necrosis and interstitial fibrosis than control group. Regarding RI, LS group showed statistically significant higher expression of all RI than other groups (p value <0.05). Also, LS group showed statistically significant higher expression of Ki-67 than both groups at 1, 3, 7 and 14 days post renal IR injury (p Values < 0.05). (Figure 2)

Conclusions

Local sildenafil administration; beside its role in renal protection against IR, enhances renal regenerative capacity after release of ischemic insult.

Funding

no funding

Introduction

Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NF?B and STATs (IL-17, TNF?, and IL-6) and leads to a synergistic production of chemokines, growth factors, and cytokines. IA was essential for the development of inflammation in various autoimmune disease models. More recently, IA was critical for the development of chronic rejections both in murine models and human allogeneic lung transplantations (J Immunol. 189, 1928 and Int. Immunol. 25, 319). The status of IA can be a new biomarker and its regulator can be a new therapeutic target in rejected kidney allografts (KA). The objective of this study was to investigate the contribution of IA during the rejection process in KA and to identify genes regulating IA.

Methods

Primary human kidney cells (PHKC) were stimulated with IL-17, IL-6, TNF?, and expressions of chemokines and IL-6 were measured by RT-PCR. Among the genes highly expressed in PHKC with IA activation, we focused on a gene named Renal NFkB Enhancer-1 (RNE1). A deficiency of RNE1 suppressed chemokines and IL-6 after IA activation in PHKC, indicating that RNE1 might be a positive regulator in IA. In another experiment, urinary RNE1 in kidney transplant recipients (KTR) were measured by ELISA and clinical data (serum creatinine, CRP, urinary protein, urinary albumin, urinary NAG, and eGFR) were also compared among the KTR patient groups with normal histology, interstitial fibrosis and tubular atrophy (IF/TA), or chronic active antibody-mediated rejection (CAAMR).

Results

PHKC expressed excess amounts of chemokines and IL-6 after IA activation by IL-17, IL-6, and TNF?. Urinary RNE1 in KTR showed significantly higher amount in CAAMR patients (48606 ng/mgCre, n=9) compared to IF/TA (10744 ng/mgCre, n=21) and normal (6081 ng/mgCre, n=13). In contrast, serum creatinine, CRP, eGFR, U-NAG levels showed no significant difference among patient groups.

Conclusions

IA was activated in PHKC, and urinary RNE1 was elevated in rejected KA. These results suggested that activation of IA is involved in KA rejection, and RNE1 could be a new biomarker. Now, we are planning to examine detailed molecular mechanisms how RNE1 regulates NF-kB pathway in kidney cells and to examine if it will be a new therapeutic target for allogeneic kidney transplantations._x000D_ _x000D_

Funding

none

Introduction

The use of computerized tomography angiography for donor evaluation has resulted in the increased detection of incidental nephrolithiasis in living renal donor candidates. This study aims at reporting the epidemiology of asymptomatic renal stones in healthy live related potential donors as well as the management strategy and long-term outcome of kidney recipients with asymptomatic stones in donors.

Methods

2200 potential donors, between 2000 and 2015 were evaluated for the presence of asymptomatic renal stones. They were subjected to abbreviated metabolic panel for stone disease along with a detailed clinical history. Donors with stones > 15 mm, significant metabolic abnormalities and presence of associated risk factors for recurrent stone disease were rejected. Finally, 36 donors with stones, proceeded for donation with stone size of 2-15 mm (group I: stone ? 4 mm, n=17; Group II: stone 5-15 mm, n=19). Patients of group I were accepted for donation with stones in situ whereas, patients of group II were treated for stones prior to donation. Records were analyzed for recipient outcome, with special attention to stone events, as well outcome of donors in terms of stone recurrence in residual kidney.

Results

Prevalence of asymptomatic renal stone in potential donors was 4.2 %. Mean age of the donor was 42.5±10.5 years with mean GFR of the transplanted kidney being 38±5.5 ml/min. In group I, follow up imaging revealed seven, four and one patients had residual stones (all ? 4 mm) at 1 month, 3 month and one year respectively. Similarly, in group II, five, three and one patient had residual stones (?6 mm). Except one, none of the recipients had stone related events in post transplant period. One patient of group II required ureteroscopic stone retrieval in post transplant period. The mean serum creatinine of the recipients at 3 months and one year was (1±0.25) mg/dl and (1.45±0.4) mg/d respectivelyl. With a mean follow up of 6.5 years, donors did not show any stone recurrence in the residual kidney.

Conclusions

Transplantation of kidneys with small, asymptomatic renal stones in situ can be safely done with adequate post-operative follow up. Donors that donated the stone-bearing kidney fared equally well in terms of recurrence of stone in residual kidney.

Funding

None

Introduction

Both estimated split renal function measured by DTPA renography and kidney volume measured by MDCT can be used to predict postoperative renal function in kidney donors. We compared predicted post donation eGFR which was estimated by split renal function and renal volume with measured eGFR.

Methods

From January 2013 to May 2015, a total of 303 living kidney donors were analyzed. All donors underwent preoperative DTPA renography and MDCT scan. Bilateral renal cortex volume was measured by 3-dimension MDCT(Fig 1.). We estimated DTPA-eGFR(Remained split renal function(%) x preoperative eGFR) and Vol-eGFR (remained renal volume/total renal volume (%) x preoperative eGFR) and analyzed with DTPA-eGFR, Vol-eGFR and MDRD eGFR(1 week, 1 month, 3 month, and 6 month postoperatively). Also, we compared DTPA-eGFR and Vol-eGFR with ?eGFR.

Results

The mean value of DTPA-eGFR was 52.97±10.32 (ml/minute/1.73 m2) and Vol-eGFR was 51.26±10.26 (ml/minute/1.73 m2). Predicting dominating side was not agreed in 113/303 (37.3%). The MDRD eGFR showed a statistically significant correlation with total renal volume, DTPA-GFR and Vol-eGFR (p<0.001; Table1). ?eGFR shows significant correlation with total renal volume, DTPA-eGFR and Vol-eGFR(p<0.001). There were 101 patients who were eGFR less than 60ml/minute/1.73m2 at 6months after donor nephrectomy. Receiver operating characteristic (ROC) was performed to predict possibility of eGFR less than 60ml/minute/1.73m2 at six months with DTPA-eGFR and Vol-eGFR. DTPA-eGFR (AUC=0.858 p<0.001), and Vol-eGFR (AUC=0.878 p<0.001) could predict CKD III at 6 months (Figure1).

Conclusions

MDRD eGFR, Vol-eGFR, and DTPA-eGFR showed a statistically significant correlation. Moreover, Vol-eGFR and DTPA-eGFR were observed high prediction ability for CKD III at six months. In conclusion, Vol-eGFR was good predictive value for renal function recovery, and thus MDCT might substitute for DTPA renography in planning donor nephrectomy.

Funding

none

Introduction

The organ shortage is the major problem in kidney transplantation. To overcome this obstacle, kidney transplants of the marginal donor, cardiac death (DCD) and extended-criteria donors, were increasing. In this setting, the prevention of ischemia-reperfusion injury (IRI) is important for both early and long-term allograft function. Hydrogen Sulfides (H2S) have recently been reported to demonstrate both anti-inflammatory and cytoprotective effects. However, the efficacy and safety of H2S has yet to be elicited in a large animal model. We investigated whether H2S administration was effective for control of renal IRI and optimal administration method in a large animal model.

Methods

Female, MHC-inbred, CLAWN miniature swine (n=8) underwent renal ischemia for 120-minutes by occlusion of the left renal artery and vein. Group 1 animals (n=3) underwent renal ischemia exclusively without any additional treatment. Group 2 recipients (n=2) received 1.1 mg/kg of intravenous Na2S 10-minutes prior to kidney reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion. Group 3 recipients (n=3) underwent selective renal artery administration of 1.1 mg/kg of Na2S 10-minutes prior to reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion via the supra-renal aorta with concomitant occlusion of the infra-renal aorta, thus allowing for exclusive renal administration. Post-operative renal function was monitored by daily serum creatinine, analysis of circulating cytokine activity (TNF-α, IL-6 and HMGB1) to measure the inflammatory response to IRI and histological evaluation of renal biopsies obtained on post-operative days (POD) 2, 7 and 14.

Results

H2S administration did not result in any adverse side effects in the recipients. All animals experienced transient acute kidney injury, achieving a peak serum creatinine level by POD 3. Recipients in the untreated group had the higher post-operative serum creatinine level than selective renal H2S administration group (POD4: 4.4 vs 8.6 mg/dl, p<0.001). Pathologically, Control group still showed strongly epithelial flattering and vacuolations, congestion of PTC, and condensed tubular nuclei as a result of influence of IRI. In systemic group, the structures of renal tubule were well preserved comparatively, and those changes in selective group were obviously disappeared. Furthermore, on POD 7, specimens from selective group showed disappointment of IRI change. In selective group, the serum TNF-α and HMGB-1 level was lower than systemic group (TNF-α: 30.6 vs 85.4 pg/ml, p<0.05, HMGB-1: 2.6 vs 11.4 ng/ml, p<0.05). The mRNA expression of IL-1β was also suppressed in selective group specimen.

Conclusions

H2S administration performed safety and appeared to have potential cytoprotective and anti-inflammatory effects following renal IRI. This effect was most profound with selective renal artery administration. Further work investigating the benefits of H2S for organ procurement and preservation is warranted as this may allow for improved outcomes following renal transplantation.

Funding

none

Introduction

It was reported that some variables were revealed remain renal function after live donor nephrectomy. This study was conducted to determine the influence of visceral and subcutaneous adipose tissue on renal function in living kidney donors.

Methods

Between July 2013 and February 2015, a total of 75 kidney donors who underwent living donor nephrectomy at our institution were analyzed. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured at the level of the umbilicus using CT scan. The border of the intra-abdominal cavity was outlined on the CT image, the cross-sectional surface areas of the visceral fat and subcutaneous fat were calculated by a single urologist using Xelis CT software (INFINITT, Seoul, Korea)(Fig 1.). Renal function was estimated with the Modification of Diet in Renal Disease formula till six months after kidney donation. The relationship between preoperative visceral and subcutaneous adipose tissue and recovery of renal function was analyzed.

Results

Thirty-three donors (44%) were male, and 13 (17.3%) grafts were secured from the right side. The mean BMI was 23.5±2.6 kg/m2 and the mean preoperative eGFR was 103.0±19.6 mL/min/1.73 m2. The mean VAT was 73.0±41.6cm3; SAT was 117.5±70.2cm3, and VAT/SAT ratio was 0.7±0.5. On multivariate linear regression, preoperative eGFR, ?eGFR, and VAT/SAT ratio were independently associated with eGFR at 6th month (Table 2). A ROC curve analysis showed that preoperative eGFR, ?eGFR and VAT/SAT ratio were highly predictive of developing of CKDIII at 6th month after donor nephrectomy (AUC = 0.933, p < 0.001).

Conclusions

Pre-donation eGFR, ?eGFR and V/S ratio are associated with the development of delayed renal recovery (GFR <60 ml/min/1.72m2) 6th month after donation. VAT/SAT ratio was associated with the postoperative renal function in living kidney donors. Kidney donors with higher VAT/SAT ratio require close observation, given their predisposition to CKD III after donation

Funding

none

Introduction

To investigate the effect of a novel soluble carbon monoxide-releasing molecule (CORM) on cisplatin (CP) induced cytotoxicity and ischemia reperfusion injury (IRI) in vitro.

Methods

The effects of CORM-3 (200 µM) were compared in normal kidney epithelial cells (HK-2, LLC-PK1) and renal cancer cells (Caki1, Caki2), which were treated with CP (50~200 μM) and induced IRI. To induce IRI condition, cell plates were placed anaerobic chamber (37°C, 95% N2, 5% CO2) for 48hrs, and then cell medium was changed complete medium and incubation in 37°C humidified CO2 incubator for 6hr. The effect of CORM-3 on stimulated IRI and CP treated normal cells/RCC was the determined by measuring the cell viability (CCK assay), TNF-α mRNA induction (Q-RT PCR), protein expression of cleaved caspase 3 and oxidative stress markers including Erk1/2, JNK, P38 (western blot).

Results

Viability after IRI were approximately 40% compared with control. Protective effect of CORM-3 on IRI in vitro model was dose-dependent. Cell viability was 40% recovered in 200 μM CORM-3 pretreated cells compared with control cells. Confluent normal cells and cancer cells were exposed for 24h to CP (50~200 µM) alone or in combined with CORM-3 (12.5 ~200 µM). Protective effects of CORM-3 on CP-treated cells were weaker than those of IRI model. TNF-α mRNA induction occurs following stimulate IRI or CP exposed cells and expression of TNF-α mRNA levels decreased in CORM-3 pretreated cells. Also, IRI or CP-induced activated oxidative stress markers decreased in CORM-3 pretreated cells. CORM-3 reduced expression of c-caspase-3 which is an apoptotic marker.

Conclusions

Our data demonstrate that protective effect of CORM-3 on CP-treated and IRI model in vitro. We suggest that CO attenuates IRI and CP induced cytotoxicity by amelioration of inflammatory and oxidative stress pathways. These effects were observed in not only normal kidney cells but also renal cancer cells.

Funding

none

Introduction

Prostate cancer (PC) in renal transplant recipients (RTR) has not been widely studied and its incidence remains controversial, reported 2-5 times more than general population. The management of this disease is challenging because it is believed that RTR under immunosuppressive therapy may have increased postoperative morbidity and higher rate of tumor progression. Currently there are not guidelines or consensus about the management of this condition. The aim of the study was to analyze our experience in the management of PC in RTR.

Methods

Prospective and consecutive study in a single tertiary centre from 2003-2015. Inclusion of RTR diagnosed of PC by urinary symptoms, prostatic specific antigen (PSA), digital rectal examination, imaging and biopsies. PC assessment for staging and treatment was in agreement with the contemporary guidelines for the general population. Main outcome measures included demographics, characteristics and associated factors, type of treatment, complications, oncological outcomes and follow-up. Retrospective and descriptive analysis.

Results

During the study period 1330 renal transplants were performed, diagnosed of PC in 28 RTR (2.1%), mean age 66 years±6.6 (51-78). Type of donors were cadaveric (n=26) and live (n=2). Immunosuppressive therapy: without mTOR (n=14) and with mTOR (n=14). Mean time between renal transplantation and PC diagnosis 111 months±75 (24-270). Median PSA of 9.6ng/ml and PSA ratio 0.19. Treatment: a) Radical prostatectomy (n=20): perineal approach (n=16), laparoscopic (n=2), robotics (n=2)/ lymphadenectomy was performed in one patient; b) Radiotherapy combined with hormone therapy (n=6); c) Active surveillance (n=2). Histology: ≤pT2 (n=15), pT3a (n=4) and ≥pT3b (n=1). No graft loss due to PC treatment was reported. Complications (18%): incontinence post-prostatectomy (n=2), anastomotic stricture (n=2) and urinary fistula (n=1). Outcomes: Remission of the 85% (n=22), Biochemical recurrence after radical prostatectomy treated with salvage radiotherapy (n=4). Mortality by other causes without evidence of recurrence (n=11), loss of monitoring (n=1). Not specific mortality from cancer prostate was reported. Observed survival rates were 100% at 12 months after treatment. Mean follow-up was 61 months±37 (12-132).

Conclusions

This is the first largest series to analyze the management of PC in RTR from a single center in Spain. PC after renal transplantation could be managed as any non-organ transplant patient with the same range of therapeutic options. According to our experience, these patients has similar histopathologic evaluation, post-treatment complications, rate of remission and recurrence than non-transplant patients, without specific mortality from PC. Active surveillance should also be provided in RTR despite being under immunosuppressive treatment.

Funding

none

Introduction

Cancer development after KT is increasing, and urothelial carcinoma (UCa) incidence has been estimated 3 times higher, especially focused in bladder. However, upper urinary tract (UUT) can also be affected, both in native and less commonly in graft UUT. Management of UCa after KT is demanding because of aggressiveness and potential graft involvement. The aim of the study is to assess all UCa developed after KT, as well as treatments performed and oncological outcomes

Methods

Retrospective analysis of 1.693 KT at our institution between 1977-October 2016. Age, sex, tumor location, TNM stage, tumor grade, presence of Cis, treatments and oncological outcomes are assessed, including median Overall Survival (mOS) and cancer-specific-survival (CSS)

Results

13 patients developed 14 UCa (0.83%), 61.5% male. Median age at the moment of cancer was 62.5 years (range 40-81) and median time from KT to cancer 52.5 months (range 2-209). UCa were located in bladder (8), in native UUT (1) and in graft UUT (5). At diagnosis, only 1 patient was metastatic and 35% of the cases (5/14) had Cis associated. Regarding tumor grade, 1 was G2, 9 were G3 and 4 were G4. Pathologic stage and treatments performed for UCa after KT are detailed in Table 1. 67% patients with non-muscle-invasive bladder tumor (NMIBT) received BCG. All patients with graft UUT UCa had locally advanced tumors and were treated with graft RNU and pelvic lymphadenectomy, returning to dialysis. At present, 69.2% (9/13) are alive, and median-overall-survival (mOS) is 36 months (range 2-182). Of the total 4 deaths, 1 was cancer-related, 1 during RC postoperative course and the other 2 ESRD-related. Cancer-specific-survival (CSS) was 92% (12/13). _x000D_

Conclusions

Bladder is the most common place of UCa after KT. BCG is also a part of the treatment in these patients. Graft UUT UCa was relatively high in our study comparing to literature. It is usually locally advanced and sometimes unresectable. mOS of UCa after KT is 36 months, which is lower than other uro-cancers in this population. Treatment of this cancer is challenging and can potentially involve the graft, being necessary to remove it and so returning to dialysis

Funding

None

Introduction

In selecting living kidney donor, we need to evaluate split renal function. We routinely use Tc-99m-mercapto-acetyltriglycin (MAG3). However, all transplant programs do not use MAG3 because of its high cost and radiation exposure. Computed tomography (CT) volumetry of the kidney is a new tool to evaluate split renal function. Since CT scan is used in all transplant programs for preoperative evaluation, CT volumetry adds no cost. If we can substitute CT volumetry for MAG3, donor can avoid extra radiation exposure and save some money. We examined the correlation between MAG3 and CT volume of the kidney. Moreover, we evaluate which is a better method to predict post-operative donor&[prime]s renal function (1, 3, 12 months).

Methods

Sixty-three patients underwent donor nephrectomy from 2009 to 2016 in our institution. Those who did not perform thin slice CT (1mm), and those with follow up less than 1 year were excluded. Thirty-four living kidney donors were included in this retrospective study. Renal volume was automatically calculated by volume analyzer software (SYNAPSE VINCENT, FUJIFILM, Tokyo, Japan). The correlation was evaluated using Bland-Altman plot.

Results

Median age is 60.5 years, and the rate of male is 50%. All patients underwent left side donor nephrectomy. Preserved parenchymal volume is 139.6ml, and preserved cortex volume is 102.0ml. eGFR decreased by 36.8% from 72.0 mL/min/1.73m2 at baseline to 47.8 mL/min/1.73m2 at 1 year post-donation._x000D_ A strong correlation was observed in split function measured by between MAG3 and cortex volume (R=0.92) (Fig. 2) preoperatively. Moreover, post-op eGFR was correlated with split function measured by between MAG3 and cortex volume (Fig 3). There are no significant differences in correlation between MAG3 and CT volumetry of the kidney at the each follow-up period (1, 3, 12 months) (Fig. 3). _x000D_ _x000D_ _x000D_

Conclusions

CT volumetry is an alternative to MAG3 to evaluate split renal function and to predict postoperative renal function. It is cost effective and beneficial by reducing extra radiation exposure to a donor.

Funding

none

Introduction

Lower urinary tract malformations managed in infancy represent a particular group of kidney transplantation since it may impair the final function of the graft. Data in literature remains sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital lower urinary tract malformation.

Methods

A retrospective multicenter study from 3 French renal transplant centers included 123 transplantations in 112 patients with lower urinary tract malformations (1996-2016). Graft and patient survivals and complications were analyzed. The results were stratified according to the underlying uropathy and type of initial management during childhood.

Results

Mean age at transplantation was 32,1 years (±11,2). Were included posterior urethral valves (n= 49), spina bifida (n=21), central neurogenic bladders (n=13), bladder exstrophy (n=14), Prune Belly (n=12), Hinman syndrome (n=6), urogenital sinus (n=4) and others (n=4). The mean follow up was 7,2years. Overall the 1, 5, 10 and 15 years patients survival was 97.4%, 93.0%, 89.4% and 80.0%. Grafts survival at 1, 5, 10, 15 and 20 years was 96.6%, 87.6%, 77.3%, 60.6% and 36.4%. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (p=0.02). There were no differences on graft survival when transplantation was performed in enterocystoplasty or urinary diversions compared to a native bladder provided a well conducted bladder management.

Conclusions

Lower urinary tract malformations should be considered for renal transplantation as any other cause of end stage renal disease. Despite previous surgeries and possible bladder dysfunction, these patients should not be excluded from renal transplantation programs. Even if enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis, patients and graft survival rates at 10 years are similar to other kidney transplantation.

Funding

None

Introduction

Hypothermic machine perfusion (HMP) reduces risk of delayed graft function (DGF) and improves graft survival. Cold reduces oxygen requirement, although metabolic rate remains around 10% and consequently hypoxia would result a source of tissue damage. Hence, the concept of supplying O2 during perfusion is growing, because it would combine active circulation of dissolved oxygen in the perfusate. Oxygenated HMP could allow ATP resynthesis._x000D_ The aim of the study was to compare HMP with or without oxygen in a pig model of kidney autotransplantation, reproducing conditions of type III non-heart-beating donor (NHBD)

Methods

Porcine model of type III NHBD autotransplantation approved by animal ethical committee. 6 female pigs randomized to HMP with or without O2. Left kidney retrieval after 30 min of warm ischemia time (WIT). Kidney was cold-flushed with Celsior® and preserved in LifePort® for 22 h. Afterward, nephrectomy of the remaining right kidney and the transplant of the preserved left kidney in an orthotopic manner were performed. Perfusion conditions are measured with serial perfusate gasometry and miRNAs expression, as well as hemodynamic machine parameters. Serum levels of creatinine are measured every 2 days. After sacrifice, pathology exam was carried out

Results

Fig. 1 shows Cr evolution, with a peak 2-3 days after transplant. Oxygenated HMP (pigs 1, 5, 6) has shown nearly significant differences in flow: 73.3 vs 46.7 (p= 0.05) and RI: 0.36 vs 0.54 (p=0.05) at the end of perfusion. Fig. 1 shows histological analysis of kidneys and miR10a expression. The increased expression of miR10a (lower DCTs) that has been linked to cell proliferation and tubular repair is correlated with the presence of severe ATN in animal 2. _x000D_ _x000D_ _x000D_

Conclusions

In our preliminary results, oxygenated HMP has shown nearly significant differences in flow and RI at the end of perfusion, as well as better functional results. ATN development was linked to increased expression of miR10a that would make it a biomarker for graft outcome. Similarly, oxygenated allografts have shown lower miR10a expression correlating with less tissue damage, so they could be a useful tool for monitoring oxygen effects in kidney perfusion

Funding

None

Introduction

Sperm aneuploidy can be assessed using fluorescent in situ hybridization (FISH) and is associated with recurrent spontaneous abortion (SAB) and implantation failure. Here, we examine the relationship between elevated sperm aneuploidy on sperm FISH testing, and genetic abnormalities identified during PGS, SAB, amniocentesis, and in live births._x000D_

Methods

We identified men who had previously undergone sperm FISH testing in a single academic andrology clinic. Sperm FISH examines sperm disomy, sex chromosome disomy, and aneuploidy in autosomes 13, 18, or 21, and the sex chromosomes X and Y. Severity of aneuploidy was measured using the sum of abnormal FISH components (range 0-5, with each chromosomal abnormality considered an abnormal component). Chart review and telephone survey was performed to determine genetic outcomes of conceptions of men who had sperm FISH testing. The survey inquired about any PGS results, karyotype results for SABs or amniocenteses, about the general health of offspring, and whether any offspring had trisomy 13, 18, or 21._x000D_ _x000D_

Results

We interviewed 99 couples; 46 couples had 175 genetic evaluations for product of conception. Ten couples provided PGS results for 102 embryos (mean±SD female age 35.8±5.7 years). Of these, 61 embryos (59.8%) were abnormal; 44.2% had monosomy, 29.5% trisomy, 11.5% tetraploidy, 3.3% chromosomal region duplications, and 11.5% were burst embryos. In couples with >3 abnormal FISH components, 66.7% of embryos were abnormal (weighted mean female age 35.7±4.0 years), while in couples with ≤3 abnormal FISH components, 45.2% of embryos were abnormal (weighted mean female age 31.3±6.4 years) (p=0.132). Fifteen couples had karyotype analysis of the conceptus after SAB, with 2 reporting a normal karyotype, 4 reporting trisomy 21, and 9 with karyotype findings that were incompatible with life. Miscarriages occurred at a mean of 7.2±2.9 weeks of gestation. Fewer chromosomal abnormalities were observed in pregnancies continuing beyond 15 weeks; all 6 amniocenteses performed were normal. Within our cohort, 52 live births were reported. Only one child had a genetic abnormality, having trisomy 21. Maternal age at conception was 25 years and the father had 5 abnormal FISH components. No deaths or significant health issues were reported for any live births.

Conclusions

Elevated sperm aneuploidy has increased risk of abnormal embryos compared to couple with less elevated sperm aneuploidy. Within this cohort, only normal embryos resulted in live births. Thus, couples with abnormal sperm FISH results should be counseled on the high rate of potentially abnormal embryos. _x000D_

Funding

AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR to DJL) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund.

Introduction

Non-coding RNAs (ncRNAs) are emerging as important but poorly understood regulators of mRNA transcription and translation. However, common library preparation techniques for RNA sequencing selects for coding mRNAs by the presence of a poly-A tail; thus, by excluding non-PolyA ncRNAs, many biologically significant transcripts may be overlooked by using this method. The objective of this study was to evaluate differences in testicular RNA identification using 2 different methods of library preparation: polyA and ribosomal RNA depletion (RibZero) using Illumina kits.

Methods

Total RNA was extracted from 3 human testis samples and processed using two different methods of library preparations: one based on polyA tags, and the other on depletion of ribosomal RNAs. The cDNA libraries were then sequenced at the same depth and annotated to known published databases. Identified transcripts were divided into two groups based on presence in one of the library preparation methods but not the other. Clinical and biological significance of identified genes was examined using the DAVID. Failure of detection of RibZero-only genes by RNAseq using polyA preparation was then confirmed by analyzing results of RNAseq in 64 testicular samples from normal patients, men with sertoli cell only (SCO), early and late maturation arrest and hypospermatogenesis.

Results

61 genes were detected only using polyA method with no detection in RibZero group (p=0.05): 17 of them belonged to small nuclear RNAs (snRNAs), 12 were snRNAs hosting genes, 3 humanin like proteins, and 3 were miRNA hosting genes: MIR137HG, MIR17HG, MIRLET7DHG. Deletion of MIR17HG leads to Feingold syndrome in humans and animal models. 74 genes were identified exclusively in RibZero group and not identified in the polyA group. The top 4 genes identified exclusively by RibZero were TAS2R50, MAGI1-AS, HIST1H3I, HIST1H4K. HIST1H4K was then further analyzed and its expression was highly abundant and specific to pachytene spermatocytes. Important components of the miRNA processing complex: AGO1,2, and 3 were expressed at >2x higher level (p=0.03) in ribosomal RNA library depletion preparation then polyA prep.

Conclusions

PolyA tail RNA enrichment method fails to adequately detect at least 7% of important RNAs in the human testis. Including ribosomal depletion RNA library preparation in addition to polyA tags enrichment is an important step to more comprehensively evaluate ncRNAs and testicular function.

Funding

P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund

Introduction

High sperm DNA fragmentation rates reduce pregnancy rates and are related to higher rates of pregnancy loss. Sperm DNA fragmentation rates above a DNA Fragmentation Index (DFI) of 30% is associated with lower pregnancy rates. There have been suggestions that more frequent ejaculation may reduce sperm DNA damage. Our study seeks to determine whether a second ejaculate provided on the same day has lower DNA fragmentation rates. _x000D_

Methods

Men provided 2 semen samples approximately 4 hours apart for analysis. In addition to the regular semen testing, sperm DNA fragmentation rates were measured using the sperm chromatin structure assay and reported as the DNA Fragmentation Index (DFI).Data analysis was performed using a Student’s T-test .

Results

A total of 54 men, mean age of 38.6 +/- 5.9 (SD) years old provided double ejaculates. The DFI in the first and second ejaculates was 38.6 +/- 21.2% and 35.5 +/- 21.2% (p < 0.001). For those with DFI < 30% on the first semen sample, the mean DFI decreased from 19.8 +/- 5.8% to 17.1 +/- 5.7% (p<0.001), while for those with initial DFI > 30%, the mean DFI decreased from 51.5 +/- 17.8% to 47.1 +/- 19.3% (p<0.001). There were a range of changes in DFI, with 8/54 (15%) found to have decreases of DFI >10% in the second ejaculate. For the men with elevated but not extremely high DFIs (DFI range 30-40%) found with the first semen specimen, the DFIs were reduced to the normal DFI (DFI <30%) range in 64% (7/11) of the men with the second semen sample. _x000D_ _x000D_ As expected, semen volume was significantly lower on the second sample 2.3 +/- 1.3 mL vs 1.5 +/-0.9 mL (p<0.001) as was the total motile sperm count (TMC) decreasing from 20.5 +/- 40 to 9.6 +/- 17.1 X 106 (p=0.003). 23/54 men had initial TMCs > 5 X 106, with 6/23 declining to < 5 X 106 in the second sample. 29/54 had TMCs above zero but less that 5 X 106 for both the first and second semen sample. 2/54 (4%) had TMC = 0 with the first semen specimen, which increased to a mean of 0.9 X 106 with the second sample. _x000D_

Conclusions

This is the first prospective study to identify significant improvements in sperm DFI rates in the second sample from men providing a double ejaculate. Testing men for changes in DFI rates with double ejaculates should be considered in those with high sperm DFI rates.

Funding

none

Introduction

This study aims to explore the association between the methylation status of the vdac2 gene promoter region and IAS.

Methods

Twenty-five patients with IAS and 27 fertile NZ were evaluated. GC-2spd cells were treated with different concentrations of 5-Aza-CdR (5, 10 and 15 ?mol/L) for 24 and 48 h. Real-time polymerase chain reaction was conducted to reveal whether or not vdac2 gene expression is regulated by methylated modification. After predicting the promoter region, dual-luciferase activity detection was used to verify vdac2 promoter activity in GC-2spd cells. Bisulphite genomic sequence was used to analyze DNA methylation of the vdac2 promoter.

Results

vdac2 expression was significantly increased in men treated with 15 ?mol/L 5-Aza-CdR for 48 h compared with that in the other groups (P < 0.05). Strong activity of the promoter (?2000bp to +1000bp) was detected by dual-luciferase activity detection (P < 0.05). Bisulphite genomic sequencing indicated that the percentages of uncompleted, mild and moderate methylation in normozoospermic men were 83.65% ± 5.51%, 8.73% ± 1.38% and 7.61% ± 5.68%, respectively. Moreover, the percentages of uncompleted, mild and moderate methylation in patients with IAS were 76.01% ± 6.94%, 7.14% ± 1.86% and 16.62% ± 8.27%, respectively (P = 0.005, 0.02 and 0.003, respectively). Correlation analysis showed that PR was associated with uncompleted methylation and negatively related to moderate methylation.

Conclusions

High methylation of the vdac2 promoter CpGs could be positively correlated with low sperm motility. Abnormal methylation of vdac may be related to idiopathic asthenospermia.

Funding

none

Introduction

A significant number of couples initiate fertility treatment with unmedicated and medicated intrauterine insemination (IUI) cycles. Previous published studies have suggested that low strict morphology scores are correlated with cycle failure. In an extremely large cohort, we sought to analyze whether strict morphology was correlated with results, and further analyzed the confounding variable of female age in correlation with cycle outcome.

Methods

In this retrospective study, couples undergoing an IUI cycle from December 2000 to October 2016 were reviewed. Sperm morphology scores were determined via Kruger&[prime]s strict criteria. Male partners were segregated by percent normal sperm morphology. Females were segregated by age (A: <35, B: 35-37, C: 38-40). Females greater than age 40 were excluded from the analysis. Pregnancy rates (PR) were determined by the presence of bHCG circulation in the blood stream (positive bHCG). Student&[prime]s t-test and chi-square analysis were performed with significance set at p<0.05.

Results

IUI cycles (n=23,035) that met the study&[prime]s inclusion criteria were evaluated. Overall, 4,019 IUI protocols resulted in achieving a positive pregnancy outcome (PR: 17.45%). In females <35, pregnancy rates rose steadily (PR: 13.4-24.3%) as percent of normal sperm morphology increased (% Normal Sperm: 1-11%). A similar trend was observed in older female cohorts (Age: 35-37; 38-40), albeit to a lesser degree (PR: 11.4-19.1%; 9.6-19.5% respectively) than the youngest cohort. Overall, a significant decline in pregnancy rate was between all patient age cohorts (<35-40) when the percent normal sperm morphology was ≤ 4% versus > 4% (PR: 14.4% versus 19.3%)(p<0.05).

Conclusions

Female age and sperm morphology have an influence on IUI pregnancy potential. This study demonstrated that females <35 to 40 can successfully utilize an IUI approach, albeit their cycle’s chances of success appear to diminish in the presence of low percentages of normal sperm morphology. This study confirms the utility of strict Kruger morphology criteria in counseling couples regarding their expected success with IUI intervention.

Funding

None.

Introduction

It has been reported that many testis-specific functional genes are drastically expressed during spermatogenesis, and defects in their expression cause male infertility. Haspin, encoding a germ cell-specific protein kinase, was cloned from a subtracted cDNA library constructed from mouse testis. Genomic analyses revealed that mouse Haspin is an intron-less gene located within the 26th intron of the integrin alpha E (Itgae) gene on chromosome 6, which is conserved in rats and humans. It was shown that human HASPIN phosphorylates histone H3 at threonine 3 and is required for this phosphorylation event in mitotic cells. HASPIN is found at the centrosomes and spindles during mitosis, where it integrates the regulation of chromosome and spindle function during mitosis and meiosis. The present study assessed whether HASPIN is a cause of infertility in Japanese males.

Methods

Japanese subjects with nonobstructive infertility (n = 282) were divided into subgroups according to their degree of defective spermatogenesis: 192 (68%) of these patients had nonobstructive azoospermia, while 90 (32%) had severe oligospermia (<5 × 106 cells/ml). The control group consisted of fertile males who had fathered children born at a maternity clinic (n = 262). Their HASPIN coding sequence (CDS) was screened by the direct sequencing of PCR amplified DNA. This study was conducted with approval from the institutional review board and an independent ethics committee at Osaka University.

Results

Polymorphisms were found at 10 positions within the HASPIN CDS. Among those polymorphisms, there were six nt changes causing an amino acid substitution, one insertion (TCCCGACGA) leading to the addition of three amino acids (aspartic acid- aspartic acid-proline: DDP), and three silent mutations. There were no correlations among the polymorphisms in terms of their co-occurrence. Three single nucleotide polymorphisms (SNPs) (c365C > A, c560T > C, and c2205A > G) and the insertion resulting in three additional amino acids (c204-/TCCCGACGA) were identified in Japanese males for the first time. Unexpectedly, c2143G > A (rs376754182) was present only in homozygous form in the infertile group.

Conclusions

In this study, we found 10 polymorphisms within the HASPIN CDS. Among those, 5 were found only in the infertile group, 3 of which were nonsynonymous. These polymorphisms found only in the infertile patients may be a cause of male infertility, although significant differences in the frequencies of the genotypes were not identified. This is the first analysis of HASPIN genetic polymorphisms in male infertile population and these results will contribute significantly to future large-scale studies on the genetic background of infertility in Japanese males and on functional analyses of the role of HASPIN in cell cycle progression.

Funding

none

Introduction

Testicular cancer is the most common malignancy affecting men in their fertile years. One in ten are azoospermic, when banking sperm, at initial presentation. Knowledge of patients' fertility potential and sperm count, prior to orchidectomy, may allow potential sperm retrieval from the testis removed during surgery. We assessed orchidectomy specimens to identify whether spermatogenesis was present in malignant testes, and what features affected spermatogenesis.

Methods

A retrospective review of 103 radical orchidectomy specimens for germ cell tumours, from 2011 to 2016, by a single expert pathologist (CH), was conducted. Tumour stage, type, volume, presence of testicular microlithiasis (TML) and the relationship to spermatogenesis (focal/widespread) were assessed and compared using Chi Square (significance p<0.0.5).

Results

Overall spermatogeneis was seen in 72/103 (70%), it was focal in 27/72 (38%) and it was widespread in 45/72 (62%). Neither tumour type (seminoma vs. non seminoma, p=0.87), stage (T1 vs. T3, p=0.09), nor presence of TML (p=0.12) were significantly related to spermatogenesis. The percentage volume of testis affected by tumours did significantly correlate with spermatogenesis (28.3% with sperm vs. 48.4% when no sperm found, p=0.05)._x000D_ _x000D_ _x000D_ _x000D_

Conclusions

Spermatogeneis is present in the majority of testes affected by germ cell tumours (70%), and it does not appear to be related to any tumour pathology, apart from percentage tumour volume. Sperm extraction at the time of orchidectomy is a sensible approach, as testis specimens, destined for the pathology lab, would otherwise be a waste of functionally viable tissue. Given that spermatogenesis was focal in 38%, sperm retrieval is best performed with a microTESE (onco microTESE) to allow identification of these small foci. In our own experience, we have found sperm in 60% of patients with testicular tumour and azoospermia, at first presentation, using this technique. A change in focus to identify the azoospermic patient, prior to orchidecotmy, is vital to allow such an approach to be adopted.

Funding

None

Introduction

Lactoferrin (LF) is abundant in human seminal plasma and on sperm surfaces. However, lactoferrin receptor (LFR) on human spermatozoa has not yet been reported.

Methods

To study the expression, localization and characteristics of LFR on human spermatozoa, different experimental approaches were applied: LFR gene was amplified from a human testis cDNA library and recombinant LFR (rLFR) protein was produced in the expression vector Escherichia coli BL21 (DE3); human sperm membrane proteins were extracted and analysed via Western blot; the binding of LF to LFR was investigated by Far-Western blot, immunoprecipitation and autoradiography analysis and the localization of LFR on sperm surfaces was detected using immunofluorescence.

Results

LFR gene was amplified from a human testis cDNA library and the molecular weight of rLFR was 34 kDa. The native LFR on human spermatozoa was a 136-kDa tetramer which was anchored to the sperm head and mid-piece through glycophosphatidylinositol. LF could bind to LFR competitively in vitro.

Conclusions

As far as is known, this study has elucidated for the first time that LFR was expressed at the testis level, was anchored to the sperm membrane by glycophosphatidylinositol during spermatogenesis. LFR may play important roles through binding to and mediating LF.  

Funding

None

Introduction

Klinefelter syndrome (KS) is characterized by the presence of an additional X chromosome (47,XXY) and leads to sertoli cell only (SCO) histological phenotype. Age dependent progressive hyalinization observed in men with KS and SCO is not seen in 46,XY men with SCO. Hyalinization in KS is believed to play a significant role in age dependent decline in sperm recovery during microscopic testicular sperm extraction. The objective of our study was to evaluate if there are genes differentially expressed between men with KS (47,XXY) and men with 46,XY and histological pattern of SCO. Therefore, providing insight on the role that the additional X chromosome contributes to progressive testicular hyalinization in men with KS. _x000D_ _x000D_

Methods

Total RNA was extracted from tissue harvested during microscopic testicular sperm extraction (mTESE) from patients with NOA and KS, and SCO as well as normal testicular tissue. RNA libraries were sequenced on an Illumina HiSeq 2000 platform. Results were mapped to the genome and transcriptome using TopHat (v2.0.8). Cufflinks was then used to quantify the number of reads. RNA Seq data was expressed as FPKMs and normalized using a TMM, JMP genomic was used to identify differentially expressed (DE) transcripts at FDR = 0.001._x000D_ _x000D_

Results

Testicular tissue from 6 patients with KS 47,XXY SCO, 11 with SCO and 10 with normal spermatogenesis were harvested, processed and sequenced. Using a clustering analysis, RNA expression in SCO 47,XXY was most similar to SCO 46,XY. 10,777 genes were found to be DE between SCO and normal controls largely representing genes expressed in germ cells. However when men with SCO 47,XXY were compared to men with SCO 46,XY we identified that only 546 transcripts (5%) were differentially expressed between these two groups despite both having SCO histology. Further analysis demonstrated downregulation of CELA2A and CELA2B as well as PRSS12 in men with SCO and KS as opposed to men with SCO and normal karyotype. These genes are known to code for serine proteases involved in elastin and collagen metabolism. Elastin and Type 4 collagen are known to contribute the characteristic hyalinization of KS tubules. Therefore, loss of these genes in men with KS may explain age dependent progressive hyalinization of tubules observed commonly in KS. _x000D_ _x000D_

Conclusions

Hierarchical clustering of gene transcripts demonstrates that 46,XY and 47XXY men with SCO share very similar expression profiles. Reduced expression of CELA2A, CELA2B and PRSS12 in men with KS may explain age-dependent progressive hyalinization of seminiferous tubules among these men._x000D_

Funding

P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund

Introduction

Despite the necessity of semen analysis on diagnosis and treatment of infertile couples, male partners are hesitant to receive outpatient services for infertility claiming pressure of business and embarrassment. As a result, in many cases, only female partners seek examination and treatment, and are thus forced to bear a great psychological and physical burden. In response to this situation, we validated the usability of a portable computer-assisted sperm analyzer(CASA) system utilizing a smartphone as a camera and an analyzer, an app, and a microscopic lens integrated with a semen specimen chamber(Figure 1). Using this system patients themselves can measure sperm motility as well as sperm concentration at home(Figure 2).

Methods

A total of 100 semen samples obtained from volunteers who had visited our outpatient clinic because of infertility were used in automated analysis for sperm concentration and motility after obtaining written informed consent. After adjusting the system through measurement of first 13 semen samples, we compared the results of succeeding 87 samples between the system and visual observation, then calculated correlation coefficients for sperm concentration and motility between them. Measurement of first 70 samples were conducted by embryologists and next 30 samples by patients themselves. The smartphone used was an iPhone 6.

Results

The correlation factor between the results of the measurement with the system and those with visual observation was 0.76 for sperm density and 0.65 for sperm motility. There were no particular problems with patient use of the system.

Conclusions

We are confident that this portable CASA system plays a role in motivating infertile men to visit clinics, thus resulting in early diagnosis and treatment. It is also hoped that this system contributes to a decrease in the mental and physical burden for women on the infertility treatment, a shortening of the time required to achieve pregnancy and a decrease in medical expenses.

Funding

Scholarship donations

Introduction

Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood.

Methods

Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. The transcriptome of the testicular homogenate using the Illumina platform were expressed as fragments per kilobase. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin’s solution-fixed sections. Apoptosis of germ cells was assessed by TdT-mediated digoxygenin-dUTP nick end labelling (TUNEL). Expression and localization of H3.5 were compared with patient background, germinal stage and PCNA expression.

Results

In normal spermatogenesis testes, the H3.5 protein was mainly localized in leptotene spermatocytes, independent of germinal stage. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p<0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p<0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy.

Conclusions

Different from other testis-specific histones, which are often expressed during the histone to protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.

Funding

none

Introduction

Atrophy of seminiferous tubules (ST) and thickening of lamina propria (LP) are the major histological findings in testes with impaired spermatogenesis, and are variably present in patients with Sertoli cell only syndrome (SCOS). However, the clinical significance of the different degrees of ST atrophy and thickening of LP is unknown. In this study, we assessed ST atrophy and thickening of LP according to age and serum hormone levels in men with SCOS.

Methods

A total of 2,179 seminiferous tubules of 15 patients without any known etiology such as cryptorchidism or chromosomal anomalies who were diagnosed with SCOS by testicular biopsy during microdissection testicular sperm extraction (micro-TESE) were assessed. Diameter of ST and thickness of LP were measured in cross-sections, and average values were calculated in each patient. Correlation between these histological parameters (diameter of ST and thickness of LP) and patient age or serum hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and total testosterone [TT]) levels were assessed using Pearson's product-moment correlation coefficient.

Results

The mean diameter of ST and thickness of LP were 97.2 ± 32.0 (range 19.0 – 212.5) µm and 13.3 ± 6.3 (range 2.0 – 39.0) µm, respectively. There were no significant correlations between diameter of ST or thickness of LP and serum LH or FSH levels. Diameter of ST had significant negative and positive correlations with patient age (Figure A) and serum TT levels (Figure C), respectively. Similarly, thickness of LP had significant positive and negative correlations with patient age (Figure B) and serum TT levels (Figure D), respectively.

Conclusions

Our results indicated that degeneration of ST in patients with SCOS progresses with aging. Immediate planning for micro-TESE is necessary for patients with azoospermia.

Funding

none

Introduction

Testicular torsion makes testis ischemic. Surgery is immediately needed to reestablish blood flow. Even if the surgery succeed, testicular atrophy is often appear and lead to spermatic dysfunction. However, the etiology is still controversial in terms of pathophysiological changes. Recently it was reported that loss of the formation in any tissue after ischemia-reperfusion (IR) was involved in necroptosis, which is one of programmed cell death series. Necrostatin-1 (Nec-1) blocks both necroptosis and indoleamine 2,3-dioxygenase (IDO). In our previous research, we elucidated that IDO inhibitor decrease inflammation in testis and epididymis. First, we investigated pathophysiological change of testicular IR researching histological and biochemical phase in this study. Subsequently to the analysis, we tried to inhibit Receptor-interacting protein kinase 1 (RIPK1) and clarify a function of necroptosis in testicular IR.

Methods

Twelve weeks old ICR male mice were used in this study. Their unilateral testicular artery was clamped under general anesthesia. Declamping three hours later, their testicular blood flow were resumed. After the procedure, bilateral testes were removed in time dependent manner (at day 1, 3, 5 and 7). Histological and biochemical change were evaluated by immunostaining and ELISA methods. Spermatic analysis from the epididymal cauda were evaluated by computer aided sperm analysis (CASA). In the following research, Nec-1 4 µg/g was administrated (iv) after declamping testicular blood flow. After the treatment, bilateral testes were removed in time dependent manner. Then, histological, biochemical and semen analysis were evaluated. Sham surgery was performed as control. Their experiments were duplicated at least.

Results

Regarding histological change, invasion of lymphocyte-predominant inflammatory cells accumulated at day 3, 5 and destruction of seminiferous structure were observed at day 5, 7. Necroptosis cell using RIPK staining was abundantly expressed. In semen analysis, significant decreased spermatic concentration was observed at day 5 and 7 compared to control (p<0.05). Significant decreased spermatic motility was observed at day 1, 3, 5 and 7 compared to control (p<0.05). Interestingly, in contralateral (unaffected side) testes, significant decreased spermatic motility was observed at day 5 and 7 compared to control (p<0.05). Some candidates were picked up as molecular marker. Significant increased E-selectin expression, which is a marker of leukocyte-endothelial cell adhesion molecule, was observed at day 1 compared to control (p<0.05). Significant increased IL-6 expression, which is a marker of inflammation, was observed at day 3 compared to control (p<0.05). Significant increased 8-OHdG expression, which is a biomarker of oxidative stress, was observed at day 7 compared to control (p<0.05). Interestingly, significant increased the highest expression of E-selectin, IL-6 and 8-OHdG were observed in contralateral testes. Same results were introduced in immunohistochemical staining. After treatment of Nec-1, testicular structure were maintained and little invasion of inflammatory cells were observed. Significant decreased germ cell death (necroptosis) in seminiferous tubules were statistically observed. Significant decreased E-selectin, IL-6 and 8-OHdG were also observed. Importantly, Spermatic motility also maintained in both treated testis and contralateral testes.

Conclusions

Oxidative stress via inflammation and necroptosis should induce spermatogenetic dysfunction in IR testis. First, prominent inflammation was occurred in testicular ischemia-reperfusion model and not only expression of cytokines were increased, but also in contralateral testes. Subsequently, oxidative stress highly expressed and cell death appeared. Therefore, their change of bilateral testis would be one of pathophysiology in patients with ischemic testis. To inhibit RIPK1 would be contribute to protection of testicular tissue and spermatogenesis in IR model.

Funding

none

Introduction

Voltage-dependent anion channel (VDAC), a channel protein, exists in the outer mitochondrial membrane of somatic cells and is involved in multiple physiological and pathophysiological processes. Up until now, little has been known about VDAC in male germ cells. In the present study, the relationship between VDAC and human sperm motility was explored.

Methods

Highly motile human spermatozoa were incubated in vitro with anti-VDAC antibody. Total sperm motility, straight line velocity (VSL), curvilinear velocity (VCL), and average path velocity (VAP) were recorded. Intracellular free calcium concentration ([Ca2+]i), pH value (pHi), and ATP content were determined.

Results

Co-incubation with anti-VDAC antibody reduced VSL, VCL, and VAP of spermatozoa. Co-incubation further reduced [Ca2+]i. Anti-VDAC antibody did not significantly alter total sperm motility, pHi and intracellular ATP content.

Conclusions

The data suggest that co-incubation with anti-VDAC antibody reduces sperm motility through inhibition of Ca2+ transmembrane flow. In this way, VDAC participates in the modulation of human sperm motility through mediating Ca2+ transmembrane transport and exchange.

Funding

None

Introduction

Epidemiological data indicate that up to 13% of infertility is attributed to cigarette smoking. Nicotine is the most abundant alkaloid chemical in tobacco. We selected nicotine as a major addictive substance of tobacco and investigated its the effects in oxidative stress (OS) changes in epididymis and testis. Additionally we examined if abstinence from nicotine can reverse these changes.

Methods

Eight-week-old Wistar rats were exposed to oral administration of nicotine (15 mg/kg). One group was exposed to nicotine for 10 weeks (Nico-group) and another group was exposed to nicotine for 7 weeks followed by 3 weeks of abstinence (Abst-group). Control animals had access to fresh water. Tissue levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were evaluated both in the testis and the epididymis. Additionally, cotinine levels in the urine, serum and seminal vesicular fluid (SVF) were evaluated. Furthermore, testosterone was measured in the urine samples. Finally, immunohistochemistry was performed for OS-markers and Cytochrome P450 2A6 (CYP2A6) in epididymal tail samples.

Results

Nicotine treatment induced significant increases of MDA levels both in the testis and epididymis in Nico-group compared to Abst and Control groups. TAC was significantly lower in both epididymis and testis in Nico group compared to Abst and Control groups. Cotinine levels in urine, serum and SVF were significantly increased in Nico-group compared to Abst group. Control samples were negative for cotinine. Urine testosterone levels in Nico group were significantly lower compared to Control-group, while there was no significant difference between Control and Abst-group, neither between Nico and Abst groups. Immunohistochemistry revealed mildly stronger intensity for all OS-markers in Nico-group compared with Abst and Control groups. CYP2A6 which is the primary enzyme responsible for the oxidation of nicotine and cotinine was expressed and localized in the epithelial cells of the epididymis in Nico-group.

Conclusions

Our data demonstrate that the harmful effects of nicotine in the testis and epididymis can be reversed by abstinence. Probably treatment with an antioxidant reagent could enhance the antioxidant defenses of testis and epididymis, and further ameliorate the cigarette smoke-induced oxidative stress in both testicular and epididymal tissue. The present data can provide a helpful tool for clinicians to advice smokers, especially those who attend assisted-reproductive programs, to quit smoking.

Funding

Grant-In-Aid (KAKENHI) by the Japan Society for the Promotion of Science (25-03102).

Introduction

The use of cryopreserved of sperm cells from human and animal semen has been a described technique since the 1950s. However, the actual utilization of available cryopreservation technology for human reproduction in sexually intimate partners has been infrequently reported. We set out to examine the utilization of cryopreserved lots of sperm cells processed for males seeking this service at a multispecialty clinic in central Texas during the interval from 1988 through 2015. _x000D_ _x000D_

Methods

A retrospective chart review was undertaken of all the cryopreserved semen samples at our institution from the time period specified above. The purpose for cryopreservation and eventual utilization of the sample were recorded along with outcomes of use for insemination. The types of utilization were accumulated as proportions for different purposes. The timing for use for insemination procedures was evaluated using survival statistics. The frequency of patients arranging to destroy samples was also reported. _x000D_

Results

A total of 1361 cryopreserved semen samples and 81 testicular or epididymal tissue samples were identified. Samples were cryopreserved for 4 purposes: planned intrauterine insemination (IUI), planned in vitro fertilization/intracellular injection (IVF/ICSI), fertility preservation related to cancer treatment, or prior to military deployment. See table 1. Samples cryopreserved for IUI were more likely to be used, whereas VF/ICSI samples were more likely to be destroyed. Of note, while accounting for only a small amount of the samples, those collected for deployment were more likely to be utilized, while those collected for cancer were the least likely to be used. See table 1 for utilization detail. The longest duration from cryopreservation until use was 9.6 years in the cancer cohort. The deployment samples were typically used the earliest. IVF/ICSI samples had the highest proportion of pregnancies (35%). _x000D_ _x000D_

Conclusions

The overall utilization rate of cryopreserved samples in our patients was low (mean, 19.3%). Not previously reported, to our knowledge, was that deployment related samples were used second only to IUI and that usage was earlier compared to other than storage indications._x000D_

Funding

none

Introduction

Patients with varicocele tend to have poor sperm quality and are at higher risk of being infertile. Although the pathophysiology of infertility in males with varicocele has been extensively studied, the underlying mechanism remains unclear. Oxidative stress has been recognized as a possible mechanism. We therefore performed a study to determine the correlation between oxidation reduction potential (ORP) and poor semen quality in infertile men with varicocele.

Methods

318 infertile men with varicocele and 51 normal healthy men were recruited as the control group. Patients with varicocele were further divided into three groups according to the clinical grade of their varicoceles (grade1-3). Semen samples were analyzed using WHO 5th edition guideline and ORP levels were measured by MiOXSYS analyzer. The results were compared by Wilcoxon rank sum test and Kruskal Wallis test and a P value < 0.05 was considered significant.

Results

Table 1 summarized the results of semen parameters and ORP levels between study groups. All semen parameters (concentration, total motility and normal form of sperm) were all found to be lower in patients with varicocele while the ORP levels were significantly higher in patients group. ORP levels were negatively correlated with sperm concentration, motility and morphology (Figure 1). Comparing patients by the severity of varicocele showed no significant differences (Table 2).

Conclusions

ORP plays a role in the pathophysiology of varicocele associated infertility. Treatment targeting on ORP reduction may potentially improve semen quality in these patients.

Funding

None

Introduction

About 10-15% of all infertility patients are diagnosed with idiopathic infertility. Particularly, long term smokers often suffer from a reduction of basic sperm parameters (Ramlau-Hansen, 2007). The effects of smoking on male fertility are still discussed controversially._x000D_ It was shown, that the essential binding between sperm and oviduct is based on a lectine-carbohydrate interaction (Koelle, 2012). A functional reduction of fertility could occur due to a lack of binding capacity._x000D_ Therefore, our group characterized the proteins on glycocalyx of human spermatozoa that are capable to bind sugar residues. Further it was evaluated, if smokers show a restricted sugar-binding ability compared to non-smokers._x000D_

Methods

We separated two study populations (smokers, non-smokers) out of 78 fresh human ejaculate samples. A direct staining with Mitotracker DeepRed, NucBlue (DAPI) and FITC-conjugated sugar residues (sialic acid- (SA), mannose- (MA) and fucose- (FU)) was performed. We used confocal microscopy to examine the fluorescence-marked samples. The fluorescent cells were analysed quantitatively and qualitatively within the study populations._x000D_ Additionally, we extracted the sperm's proteins from smokers and control group which we applied on SDS-Page (4-12.5 %). Western Blot was used to proof the presence of LMAN2 and CatSper1 proteins on the plasma membrane surface._x000D_

Results

We located proteins at the middle part of the spermatozoa's head that are capable of binding sugar residues._x000D_ The ratio of fluorescence-labelled cells to the total cell count, which correspond to the capacity of binding sugar residues, was measured. We showed a significant difference between the groups: For smokers, we counted a proportion of 0.07±0.006 (SA), 0.05±0.006 (MA), 0.05±0.005 (FU) compared to 0.15±0.01 (SA), 0.20±0.02 (MA), 0.19±0.02 (FU) for the non-smokers (p<0.05). Fluorescence intensity did not vary significantly between the groups._x000D_ Protein candidates were found in Western Blot but first experiments did not show a significant difference in the amount between smokers and non-smokers.

Conclusions

Our results point out, that smoking could possibly lead to a reduction of sugar binding proteins on the human sperm glycocalyx. This could be a reason for a decreased binding capacity of sperms to the female reproductive tract which could lead to a reduced fertility potential of smokers. Further work is necessary to lighten the exact molecular interaction between spermatozoa and female reproductive tract. Based on these facts it might be possible to examine new diagnostic and therapeutic approach in the future.

Funding

none

Introduction

Varicocele- associated infertile men tend to have poor sperm quality. However, the underlying pathophysiology of how it leads to poor sperm quality remains unclear. Oxidative stress (OS) has been recognized to be the possible mechanism. In order to determine the role of OS in infertile men with varicocele, we investigated the relationship between oxidation reduction potential (ORP) and poor sperm quality in this group of patients.

Methods

A total of 56 infertile men with varicocele, 132 infertile men without varicocele and 51 healthy males were recruited. The patients with varicocele were subdivided into three groups based on the clinical grade of their varicoceles. Semen analyses were performed based on the WHO 5th edition guideline. ORP measurements were obtained using the MiOXSYS analyzer. The comparisons between different groups were analyzed by Wilcoxon rank sum test and Kruskal Wallis test and a p value of <0.05 was considered significant.

Results

The mean age ± standard deviation of all patients with varicocele involved in the study was 35.3 ± 7 years. The results of sperm parameters and ORP values in patients with varicocele and normal healthy men are summarized in Table 1. Sperm concentration, motility and normal morphology were lower and ORP levels higher in patients with varicocele. However, there were no significant differences in these parameters when compared with the severity of disease (grade 1-3) or within fertile patients without varicocele.

Conclusions

Our result showed that both sperm parameters and ORP values distinguished infertile patients with varicocele from normal healthy men. The elevated ORP levels further support the role of OS as an underlying mechanism of infertility in varicocele patients.

Funding

None

Introduction

There is an association between testis cancer and male subfertility with a number of studies reporting that men with testis cancer may have abnormalities in their semen parameters, although the exact pathogenesis is unknown.The aim of this study was to determine the effects of testicular cancer on semen parameters in men prior to radical orchidectomy and the possible basis of these abnormalities.

Methods

Between 2010 and 2016, 110 men underwent sperm cryopreservation prior to radical orchidectomy. Semen parameters were measured according to 2010 WHO criteria. A multiple regression analysis was undertaken to determine the effects of age, tumour size and histopathological features including lymphovascular invasion, type of tumour and preoperative tumour markers to determine whether these factors had an effect on semen parameters.

Results

The median age of patients was 31 years (IQR 25-35). The median sperm concentration, motility and normal forms were 17.15 million/ml, 54.25% and 6.5% respectively. Seminomatous tumours tended to be weakly but significantly associated with better motility than other tumour types (p = 0.048), whereas tumours associated with higher AFP were significantly associated with poorer morphology (p= 0.02). Median AFP was 3 (IQR 2.6-12.5). Forty nine patients (44.5%) had OAT, 8 were azoospermic (7.3%) and 38 had oligozoospermia (34.5%)._x000D_ None of the other factors, including tumour size, Beta-HCG, LDH and stage were significantly associated with semen parameters. (table 1)_x000D_ _x000D_ _x000D_ _x000D_

Conclusions

44.5% of patients with testicular carcinoma have abnormalities in their semen parameters, with azoospermia in 7.3% of patients. There appears to be an association between higher AFP and morphology, although the pathological basis of these abnormalities needs further investigation, but seems to be unrelated to tumour size.

Funding

None

Introduction

We review our large singe center experience with active surveillance (AS) for cystic renal masses (CRMs), focusing on patients with ≥ 5 years (yrs) of follow-up.

Methods

We queried our prospectively maintained kidney cancer database (n = 2574) to identify patients with CRMs enrolled on AS. Estimated tumor volume (ETV) at presentation was calculated using a standard formula and linear growth rate (LGR) was evaluated. Wilcoxon rank sums were used to assess for demographic differences in growth rates and crossover to delayed intervention (DI). Kaplan-Meier curves were used to evaluate pts who crossed over to DI. A sub-set analysis was performed of patients with ≥5 years follow-up and no cross-over to DI.

Results

Of 601 AS patients, we identified 196 patients with CRMs enrolled in AS (64.3% male, median age 64.3 yrs, and mean ETV of 39.1 cm³). The median follow-up for the CRM cohort was 59.7 months. 48 patients (24%) with cystic renal masses crossed over to DI with a median time to DI of 16.7 months (IQR 10.8 - 27.7 months). When compared to solid masses, patients with CRMs (33.9% vs. 23.3%, p < 0.016) were less likely to proceed to treatment. The majority of patients (64%) with CRMs who crossed over to DI did so within 2 years. Younger patients (57.2 vs. 64.4 yrs, p < 0.001) were more likely to crossover to DI. Mean change in ETV was 5.8 cm³/yr and mean LGR was 2.6 mm/yr. Mean change in ETV of cystic masses was slower than solid masses (5.8 vs. 11.4 cm³/yr, p <0.04). A majority of patients (95.4%) were still alive at 60 months follow-up. A subset of 37 patients with CRMs had ≥5 years of follow-up without crossing over to DI. All of the patients were alive and only one patient developed distant metastasis. Mean LGR for this sub-set was 0.1 mm/yr.

Conclusions

Active surveillance with or without delayed intervention is a successful strategy in well selected patients with localized cystic renal masses. Most patients who cross over into DI are likely to do so within the first 2 years on AS. Metastasis and death are rare events in a well selected group of patients. Cystic masses grow more slowly and are less likely to proceed to intervention when compared to solid masses.

Funding

None

Introduction

Several nephrometry scores have been proposed to predict perioperative outcomes in partial nephrectomy, but for clinical uses, its been questioned as an instrument for helping in decision-making. Therefore, our objective was to compare the ability of Nephrometry scores (R.E.N.A.L., PADUA and ABC) to subjective evaluation of the image by a group of experienced urologists and a group of first-year general surgery residents in predicting surgical outcomes in patients who underwent Partial Nephrectomy.

Methods

Computerized Tomography or Magnetic Resonance preoperative images of 87 patients who underwent nephron sparing surgery were retrospectively analyzed and classified by experienced Radiologist using nephrometry scores (R.E.N.A.L., PADUA and ABC) and subjective classification of the image in low, medium or high complexity was done by a group of blinded urologists (3) and residents (3) with none experience in renal surgery. The most common classification in each group was chosen or in the case of 3 divergent findings, medium complexity was the selected option. The outcomes were postoperative complication, positive surgical margin, ischemia time, surgery lenght, bleeding, renal functional lost and hospital stay period. Chi-Squared test was used for analyzing qualitative outcomes and a Spermans correlation test was used for continuous variables.

Results

R.E.N.A.L., PADUA and ABC Score can predict surgery time (p=0.004, p= 0.003 and p<0.001) and ischemia time (p<0.001 for all). The evaluation performed by the urologists also statistically predicts surgery time (p=0.001) and ischemia time with a better correlation than the Scores (p<0.001) Table 1. The evaluation performed by the urologists was the only one capable for predicting postoperative complications (p=0.049). Regarding bleeding, positive surgical margins, hospital stay and decrease in renal function, none of the scores or subjective evaluation had statistically significant correlation.

Conclusions

Nephrometry scores can overcome a subjective evaluation done by a non-experienced surgeon. On the other hand, experienced urologists perform better than Nephrometry scores in predicting surgical outcomes when analyzing pre-operative imaging. Therefore, those scores have little utility in clinical decision-making.

Funding

none

Introduction

MRI may aid in the management of small renal masses (<=4 cm, SRM) by differentiating among histologic subtypes. However, standardized approaches to MRI interpretation and interobserver agreement data are lacking. _x000D_ _x000D_ To assess the performance of a wide spectrum of MRI features for predicting the histologic diagnosis of SRM, and determine the interobserver agreement among multiple readers._x000D_ _x000D_

Methods

Retrospective HIPAA-compliant IRB-approved study including 109 patients with cT1a SMR and a pre-surgical MRI. Images were reviewed by 7 radiologists with body MRI training and 1-15 years of experience. The following characteristics were analyzed on non-contrast images: T2-weighted (T2W) signal intensity/texture, presence/absence of intravoxel or bulk fat, magnetic susceptibility, central scar, and hemorrhage. Features assessed on post-contrast images included contrast avidity, enhancement homogeneity, dynamic characteristics, and segmental enhancement inversion. Multivariate generalized linear mixed model analysis with logit link was used to identify independent subtype predictors, as confirmed by histopathology, with p < 0.05 considered significant. Pairwise weighted analysis was used to measure interobserver agreement._x000D_

Results

Clear cell renal cell carcinomas (ccRCC) represented 51% of the masses, papillary RCC (pRCC) 25%, chromophobe RCC (chrRCC) 6%, oncocytoma 6%, minimal-fat angiomyolipoma (mfAML) 6%, and others 9%. Table 1 includes values for the MRI features. ccRCC was predicted by signal intensity on T2W (high vs low, OR, odds ratio: 3.2 CI 95%: [1.4, 7.1], p < 0.001) and contrast avidity (avid vs. low, OR: 4.5 [1.8, 10.8], p < 0.0001), while pRCC was predicted by contrast avidity (low vs avid, OR: 0.05 [0.02, 0.2], p < 0.0001) on multivariate analysis. Segmental enhancement inversion was an independent predictor of oncocytoma (present vs absent, OR: 16.2 [1.0, 275.4], p < 0.05). None of the features were significant predictors of chrRCC or mfAML on the multivariate analysis. _x000D_

Conclusions

Our data support the use of T2W signal intensity and contrast avidity as critical steps in the implementation of standardized MRI interpretation algorithms for predicting the histological subtype of SRM. Segmental enhancement inversion can be used as a feature for the diagnosis of oncocytomas.

Funding

Partially funded by grant 5RO1CA154475

Introduction

Underlying disorders associated with Microscopic hematuria (MH) vary from benign conditions to more serious causes such as urinary tract malignancies. American urological association has issued an updated guideline on asymptomatic MH in 2012, addressing this heterogeneity and emphasizing on detection of urinary tract malignancies. The recommended protocol includes cystoscopy and multiphasic computerized tomography urography (CTU) in all patients older than 35 years. Low detection rate of malignancies in patients with MH, has questioned the necessity of performing full evaluations and exposing patients to the risks of radiation, allergic contrast reactions and contrast-induced nephropathy, as well as, imposing financial burdens to the health systems. We conducted this study to evaluate the efficacy of various urologic investigations in determining etiology of MH in young adults.

Methods

In this multi-institutional study, we retrospectively analyzed the records of 408 patients younger than 50 years with unexplained MH who underwent cystourethroscopy between December 2008 and January 2016. Furthermore, results of upper urinary tract investigations, including CTU or intravenous urography (IVU) and ultrasonography, as well as urine cytology and cystoscopy were obtained and analyzed to assess the role of each modality in determining the etiology of MH in young adults.

Results

During the study period, we identified 408 patients with MH, who underwent cystourethroscopy. Mean age of patients was 38.7±7.3, ranging from 22 to 50 years. Extensive urological evaluations revealed no pathology in 363 (89.0%) patients. However, 37 (9.0%) and 8 (2.0%) patients were diagnosed with benign and malignant pathologies, respectively._x000D_ In the present study, neither urine cytology nor upper tract imaging with CTU/IVU changed the diagnosis made by ultrasonography alone. However, cystoscopy was necessary for diagnosis of low grade bladder tumor in one patient. In multivariate analysis, age and the number of RBC/HPF were significantly associated with urothelial malignancies.

Conclusions

Our results showed that the probability of malignant pathologies is low in young patients presenting with MH. Moreover extensive urologic workup including upper tract imaging with CTU/IVU and voided urine cytology add little, if any information to that obtained by ultrasonography.

Funding

None

Introduction

Various methods are currently available to non-invasively quantify bladder volume. The goal of this project was to determine the most accurate method of quantifying bladder volume using 2D and 3D ultrasound techniques during urodynamics.

Methods

Nine female participants with OAB underwent an extended urodynamics procedure (Laborie Aquarius XT) while ultrasound images of the bladder were obtained using a 3D 6MHz transabdominal probe (GE Voluson E8). The bladder was filled with saline at a rate of 10% bladder capacity (based on an initial clinical fill) per minute while ultrasound images were captured once per minute. Bladder volume was estimated from 2D cross-sectional images in the sagittal and transverse planes assuming an ellipsoid geometry (Eqn 1, V_spheroid), assuming a shape in between an ellipsoid and a cube (Eqn 2, V_Bih by Bih et. al. 1998), and from the 3D ultrasound data obtained by tracing the bladder outline in six planes with GE's 4D View software (V_3D, Fig. 1 panel A)._x000D_ V_Spheroid= π/6 (W*H*D) Eqn. 1_x000D_ V_Bih=0.72*W*H*D=1.375*V_Spheroid Eqn. 2_x000D_ In Equations 1 and 2, W is the width (horizontal diameter) and H is the height (vertical diameter) in the sagittal direction and D is the depth in the transverse direction (horizontal diameter)._x000D_

Results

V_Spheroid was significantly lower than infused volume (V_H2O) when compared by a paired t-test. V_Bih and V_3D tended to be slightly, but not statistically, larger than V_H2O (Fig. 1, Fig. 1 panel B).

Conclusions

The bladder shape cannot be assumed to be an ellipsoid in patients with OAB. Tracing the perimeter in several 3D imaging planes better accounts for the non-uniform geometry, providing a more accurate volume measurement. Volumes estimated by V_Bih or by tracing the bladder in 3D were not significantly different from V_H2O, demonstrating that these are the most accurate methods of non-invasive assessment of bladder volume.

Funding

Support provided by NIH R01DK101719, VCU Presidential Research Quest Fund, and VCU Dean's Undergraduate Research Initiative.

Introduction

We evaluated the use of white light imaging (WLI) and narrow-band imaging (NBI) cystoscopy for the detection of bladder cancer. Additional objectives were to provide summary RGB data and to determine a relationship between cancer detection and tumor characteristics.

Methods

A prospective double blinded controlled study of NBI was conducted in 102 consecutive patients with definite or suspected bladder cancer after WLI and NBI cystoscopy by 2 urologists. Transurethral targeted biopsies were performed and the histologic outcomes were compared. We analyzed average RGB color on 3x3 pixel of the randomized 3 other points for abnormal lesions and grossly normal in bladder._x000D_ _x000D_

Results

A total of 172 biopsies for suspicious lesions (WLI+/NBI+=145, WLI-/NBI+=27) were taken. The percentage of malignancies in the sites identified only by NBI was 63.0% (17 sites).Of 15 CIS sites, 53.3% was detected by only NBI. The positive predictive value of NBI and WLI were 70.3% and 67.1%, respectively. _x000D_ Bladder washing cytology positive (HR=3.87, p=0.002). grossly papillary feature (HR=6.80, p<0.001) average blue of lesion for WLI (HR=0.96, p=0.006) were significant risk factors for detection of bladder cancer during transurethral targeted biopsy.

Conclusions

NBI is a simple and effective method for identifying CIS without the need for dyes. RGB analysis for bladder wall would be helpful for discrimination bladder cancer.

Funding

none