History of the Department of Urology Mayo Clinic RochesterHistory of the Department of Urology Mayo Clinic Rochester

Why in the world Rochester, Minnesota?

The father of Mayo Clinic, Dr. William Worrall Mayo, was born in Eccles, England, and studied medicine at Manchester, Glasgow and London before immigrating to the United States in 1845. He initially worked as a pharmacist at Bellevue Hospital in New York and as a tailor in Lafayette, Indiana, prior to completing his medical degree at Indiana Medical College in 1850. Upon graduation he was employed at the University of Missouri, medical department where he contracted malaria. His goal upon leaving Missouri was to “drive until I get healthy, die, or see no one with malaria”. Rochester, Minnesota, became his home town based upon job opportunity as a military surgeon for the regional US Army draft board and the only county in Minnesota without a natural lake (no malaria).

Out of the rubble comes a gem

Mayo Clinic emerged from the rubble of a tornado that struck Rochester, Minnesota, in August of 1883. The twister killed more than 24 individuals and injured another 40. This incident prompted the Head Mother, Sister Alfred Moes from a local convent to approach Dr. William W. Mayo to establish a hospital for Rochester. Dr. WW Mayo then 63 years of age, envisioned that his sons Dr. William J. Mayo (University of Michigan, 1883) and Dr. Charles H. Mayo (Northwestern University, 1888) would take over his practice. His vision however was more than just taking over the practice; he believed that medicine would be at a cross roads at the beginning of the 20th century and that success in a medical practice would only come about by collaboration between physicians. He instilled into his sons that a physician will need to perpetually seek for creativity with a goal toward the establishment of new and better diagnostic and surgical techniques. He therefore encouraged the two brothers to establish a joint practice, where each would practice for 9 months and then travel for 3 months, Dr. Charlie would travel in the spring, Dr. Will in the fall. These 3-month sabbaticals would be spent traveling to areas to learn new diagnostic or surgical techniques and bring them back to the practice; arguably the fi rst concept of post-graduate medical education. This habit fostered by Dr. WW Mayo, and practiced by his sons brought the concepts of listerism, (antiseptic surgery), new principles of anesthesia, roetengraphy and the cross pollination of new surgical techniques to the region. The adoption of the techniques learned elsewhere were then perfected in their practice resulting in unheard of low morbidity and mortaility rates. By the mid-1890’s the Mayo brothers and the hospital they helped establish were gaining regional, national and international recognition as a high-quality medical institution.

The vision of Urology (Drs Millet and Braasch) and Post graduate Medical Education

At the turn of the 20th century, the practice of urology was limited to the treatment and complications of gonorrhea, syphilis, genitourinary tuberculosis, bladder calculi, urinary incontinence and urinary retention. The Mayo Brothers however had a different vision. As dedicated general surgeons, they knew that the surgical techniques employed were based upon accurate diagnosis and that the diagnosis of urologic conditions were in their infancy.

It was the vision of Dr. William Mayo, who in 1898, asked Dr. Melvin Millet, (a graduate of the University of Minnesota, 1895 with an additional year of training in urology in London) to join their staff. Dr. Millet was to be the third associate outside of the brothers. Dr. Will requested that Dr. Millet dedicate his practice to diagnosis and treatment of the diseases of the urinary tract. As the habit of the brothers they sent Dr. Millet to Germany to evaluate the cystoscope that was then being used by Dr. Maximilian Nitze and to review another new technology, the X-ray machine by Dr. William Roentegen. Their purpose was to see if the combination of these two methodologies had applicability to a urologic practice.

Dr. Millet returned to Mayo Clinic with the concept of how to combine these two modalities for the diagnosis of genitourinary problems. Dr. Millet was the fi rst physician to develop a technique to use water instead of air as the medium for cystoscopy. Unfortunately, before he could capitalize on the knowledge he had gained during his sabbatical, Dr. Millet developed acute renal failure, that resulted in his untimely death at age 38 in 1907.

Shortly after Dr. Millets death, Dr. Will invited Dr. William F. Braasch to join the then 11-man Mayo group practice. Will’s vision was that Dr. Braasch would become the expert in diagnostic and therapeutic endoscopic methodology leaving any open surgery needed on the genitourinary tract to the general surgeons. Dr. Braasch, a trained internist and pathologist, with no experience in endoscopy was intrigued by the concept of how panendoscopy could revolutionize the practice of medicine and agreed to join the practice with operative privileges limited to the diagnositic and therapeutic endeavors he could perform via endoscopic methods. As Millet’s successor, he followed Dr. Will’s suggestion to visit various physicians to learn the trade of “urology”. During this time span, he spent time with Dr. William E. Lower, founder of the Cleveland Clinic, to learn diagnostic endoscopy of the genitourinary tract, Dr. Edwin Beer, who had perfected the use of “electric fulguration using a probe through the cystoscope” to destroy bladder tumors,

Dr. Leo Burger, who had modifi ed the cystoscopic lens to improve visualization and Drs. Hugh Hampton Young and JT Geraghty of Johns Hopkins to gain expertise in treating prostatic and urogenital lesions. He learned the technique of retrograde cystography and pyelography using a silver solution, a process developed by German surgeons Drs. Lichtenberg and Volecker and currently employed at Hopkins.

Following his educational journey, he returned to Rochester where he developed a diagnostic and operative cystoscope that perfected the ability to introduce ureteral catheters through separate ports that were within the cystoscope, thus enabling canalization of the ureteral orifi ces under direct vision. With minor modifi cations, the Braasch cystoscope that he developed and failed to patent was the predominant cystoscopic instrument used from 1910 to 1970. During this time span, Dr. Braasch recognized that the colloidal silver solution used for retrograde pyelography was associated with sterile abscess formations in the renal cortex if the solution had infi ltrated into the renal parenchyma. He subsequently became a major advocate to pursue the development of better techniques and different solutions for use in the radiographic assessment of the genitourinary tract. He published the fi rst comprehensive collection of genitourinary radiographic studies entitled “Pyelography” that became a instant classic in 1915. He published the fi rst pyelographic images of genitourinary tuberculosis, renal carcinoma, urothelial carcinoma, UPJ and UVJ obstruction. Dr. Braasch was the fi rst Chairman of the Division (section) of Urology at Mayo Clinic, serving in this capacity from 1914-1939. Despite an outstanding career with the publication of > 200 peer review papers, being the president of multiple organizations including the American Urologic Association, the Association of Genitourinary Surgeons, and the Minnesota State Medical Association, serving on the Mayo Board of Governors and receiving the prestigious “Keyes Award for outstanding contributions to Urology”, Dr. Braasch always believed he did not reach elite status as a urologist while practicing at the Mayo Clinic. As a pure endoscopist having not trained in open surgical techniques, he felt that he was only the handmaiden to the surgeons, never on equal footing. Dr. Braasch retired from the clinic in 1946 and died at age 97 in 1975.

The inception of Post Graduate Medical Education (Fellowships)

at the Mayo Clinic

Dr. Will and Charlie Mayo were among the fi rst physicians to recognize the need for post-graduate medical education, encouraged by their father to routinely take sabbaticals for educational purposes. Although they early on encouraged the staff to do likewise, they soon realized this would not be practical in the long term and sought to enhance post-graduate medical education on regional levels. With this in mind, Dr. Will took several of his sabbaticals to observe post-graduate medical training throughout the US and Europe during the 1907-1914 time period. During these visits he observed that interns and resident assistants were treated like “fl unkies” to the staff physician performing the “scut work” with little formal education or the opportunity to learn surgical techniques with “hands on experience” surgery usually being taught by observation alone. In 1915 Dr. Will Mayo developed several 3-year formalized fellowships (post internship and residency) at Mayo Clinic in the various specialties. The fellowships developed followed a formalized educational plan, with all of the “fellows” having to spend time in the areas of clinical diagnosis, research +/- surgery, and +/- endoscopy (depending on specialty). Weekly didactic and patient management conferences were mandatory and built into the schedule. The fi rst fellowships at the clinic were offered in the 1915-1916 school year and became an instant success.

Accidental Discovery of Genitourinary Radio-opacity of 10% Sodium Iodide

Due to the infl uence of Dr. Braash, members of the Department of Urology were always seeking better ways to visualize the genitourinary system. In this regard, Dr. Earl Osborne, a urology fellow at Mayo Clinic, decided to take radiographic studies of the abdomen after the intravenous injection of 10% sodium iodide solution, a then current treatment for patients with syphilis. Dr. Osborne when reviewing these fi lms noted that the kidneys and bladder had became opaque. He brought his fi ndings to Dr. Braasch. Dr. Braasch was concerned that the toxicity of 10% sodium iodide solution, i.e. increased renal insuffi ciency would make this solution clinically impractical for diagnostic use. He however requested that Dr. Rowntree, chairman of the Department of Medicine, be brought into the study to manage complications and then assigned a resident, Dr. Albert Scholl, to the project to help Drs. Osborne, Roundtree and Sutherland (Radiology) to study the concept. The presentation of their fi ndings and data at a national meeting in 1920 and their fi nal paper noting the radio-opacity of sodium iodide published in JAMA in 1923, is noted to be the foundation for the eventual development of radio-opaque contrast dye.

Punch (Braasch-Bumpus) Resectoscope

Dr. Hermon Bumpus modifi ed the Braasch resectoscope by adding both a Bugbee electrode to the resectoscope to control bleeding and by the development of a closed loop fl uid irrigation system that combined temperature control of the irrigating fl uid with maintenance of water pressure by a circulating pump. The later modifi cations, a entirely new concept at that time, were adapted to improve aseptic technique and reduce postoperative complications during prostatic resection. The development of the Braasch-Bumpus punch resectoscope in 1927 (Further modifi ed by Dr. Gershom Thompson in 1935) was however directly competing with the “hot loop” resectoscope developed in 1920 by Dr. John Caulk of St Louis. Although the two methodologies competed against each other for the next 40 years, the hot loop resectoscope would eventually win out.

Defending the TURP, Defi ning the TUR syndrome and the Division of Mayo

Urology helping establishment of Urology as a separate fi eld from General Surgery

From 1932-1947 urologists at Mayo Clinic performed between 800-1000 TURP’s per year. The sheer numbers of the procedure performed at Mayo Clinic by the Division of Urology was having a major impact on the regional general surgeons and prompted signifi cant national and international controversy at general surgical conferences throughout this time period. Open criticism aimed directly at Mayo Clinic Division of Urology repetitively occurred at national and international surgical meetings. This criticism came to a head when a written open challenge occurred in the British Medical Journal in early 1939. Specifi cally the editorial piece in that journal stated that Mayo urologists embraced the TURP as a procedure because it was the only way they could be considered a surgeon because they lacked open surgical skills. This criticism prompted an in-depth response from Dr. Gershom Thompson then chair of Urology at Mayo Clinic. In 1939 he authored or coauthored 38 articles in response. Within this series of papers Dr. Thompson outlined that use of the TURP for treatment of BPH compared to a single stage suprapubic prostatectomy resulting in a 75% reduction in hospital stay and a decrease in mortality from then reported national standard of mortality of 30-55% for suprapubic prostatectomy to 1% for TURP. He further delineated that 20% of the deaths following a TURP occurred due to hemolysis and an ensuing electrolyte imbalance from fl uid reabsorption, in essence becoming the fi rst to describe the TUR syndrome. These articles accomplished two important events; they prompted the search for non-hemolytic irrigating solutions and permanently established urology as a separate fi eld from general surgery.

Innovation in the Treatment of Urinary Calculi

Beginning in 1967 the Departments of Urology and Nephrology became world famous with arguably one of the fi rst metabolic stone clinics in the world that combined the efforts of the two departments in the management of stone disease. Dr. Lynwood Smith for decades led the efforts from nephrology, and although a variety of urologists worked with Dr. Smith, it was Dr. Joseph Segura that eventually led the Department of Urology in this fi eld. In 1981 Dr. Segura attended a urological conference in England and reviewed a case presentation on how a group of German physicians had inserted a guide wire from the back into the kidney and sequentially dilated up the tract 2 mm per week over a 5 week time span until they reached 10 mm. They then introduced a ultrasonic lithotripter to break up and remove a renal stone. Upon his return to Rochester, Dr. Segura contacted Dr. David Patterson (Urology) and Dr. Andrew LeRoy (Interventional Radiology) and discussed with them the concept of rapid dilation of the percutaneous tract, a practice that had already been adapted by Dr. LeRoy for placement of nephrostomy tubes. Dr. Segura subsequently suggested same-day treatment of renal calculi by the percutaneous route. Over the next year this triumvirate performed slightly greater than 1000 cases in an 18-month time span from 1981-1982 becoming one of the pioneering centers for management of urinary tract calculi in the world. Over Dr. Segura's remaining career this triumvirate, in conjunction with the Mineral and Metabolism Clinic of Dr. Smith, came forth with multiple innovations in the medical and surgical management of stone disease. Although these individuals were innovative geniuses, they did miss one pioneering moment when Dornier asked the Mayo stone group to become one of the fi rst 5 stone centers for the HM3 machine in the world. Although they rejected the initial offer, they returned to Dornier, hat in hand and became the 8th center with a HM3 machine in the United States. Due to their combined endoscopic skill and lithotripsy expertise for the etiology of stone disease, Mayo became one of the leading centers in delineating the long-term complications of lithotripsy and indications for when it should be the primary treatment modality employed. The combination of surgical skills and metabolic evaluations for the etiology of stone disease has placed Mayo as one of the primary centers for the evaluation and management of stone disease in the US and world.

Division of Urology becomes Department of Urology in 1970

Dr. Ormond Culp (chair of the division-department from 1962-1972) pushed for and received separation of the Division of Urology from the Department of General Surgery in 1970. The separation from the Department of General Surgery was cleared by the Mayo Board of Governors and was based upon the unique endoscopic skills of the urologist, the prestige of the division, and the concept that a department would allow recognition of the increased national and international stature of the urologic practice.

Controversy regarding urologists becoming open surgeons at the Mayo Clinic

The debate on the defi nition of what constitutes a urologist that began in 1939 in the British Medical Journal came to a head in 1947, when the American Board of Urology denied two graduates of the Mayo Urology Residency to sit for board certifi cation “due to failure from being trained to do open urologic surgery”. At that time all members of the Department of Urology, Drs. Thompson, Emmett, Cook, Pool and Greene were world renown for their expertise in transurethral surgery; indeed, they had developed or enhanced techniques for transurethral removal of ureteral and bladder stones, treatment of bladder tumors and benign prostate disease but were blocked by the Mayo General Surgery Department from performing open surgery. With the recognition that the Board of Urology had changed their criteria for membership in 1947 and that they were not going to recognize any physician who trained at Mayo Clinic to be eligible for board certifi cation in urology, an intense concern arose that Mayo Clinic would lose national and international prestige. Although the Department of General Surgery adamantly fought against urologists becoming open surgeons, the Mayo Board of Governors bypassed their veto in 1950 and personally hired Dr. Ormond Culp on staff. Dr. Culp had completed his residency at Johns Hopkins Hospital under Drs. Hugh Hampton Young, Hugh Jewett and William Scott, had practiced endoscopic and open urologic techniques in the US Army Medical Corp during WWII and had been on the urology staff at Henry Ford Hospital in Detroit. Urology subsequently became the third recognized surgical sub-specialty at Mayo Clinic allowed to do open surgical procedures following orthopedic and plastic surgery.

Excretory Urography (Intravenous pyelography), the Department of Urology and the Mayo Clinic

The discovery that sodium iodide was a radio-opaque substance that would allow imaging of the genitourinary tract was incidentally noted within the division of Urology at Mayo Clinic during the treatment of syphilis in 1920 and the fi ndings published in 1923. Although extensive work to fi nd alternative substances to opacify the genitourinary tract that were less toxic than sodium iodide were performed within the department for numerous decades, the eventual ideal substance used for the standard IVP, a hydrophilic non-ionic triiodinated contrast medium was perfected by Nyegaard and Company from Norway. The Department of Urology however had gained expertise in the technique for IVP and was responsible for the performance and reading of all IVP’s from 1920 until 1969. Indeed the Department of Urology, together with Kodak developed the process of nephrotomography at Mayo Clinic from 1960-1962. In 1968, the Board of Radiology came to Mayo Clinic and demanded that the performance of IVP’s be removed from the division of Urology and be given to the Department of Radiology. Although an intensive internal confl ict arose regarding this request, the Mayo Board of Governors forcibly removed the performance of IVP’s away from the Division of Urology and gave this to the Department of Radiology in 1969.

© 2012 Mayo Foundation for Medical Education and ResearchCompiled by D. A. Husmann

History of the Department of Urology Mayo Clinic RochesterHistory of the Department of Urology Mayo Clinic Rochester

© 2012 Mayo Foundation for Medical Education and Research

Innovation for IPP and AUS

In 1971 at the inception of the University of Urologic Forum (eventually the Society for University Urologists) Dr. Green introduced Dr. Furlow to Dr. Brantley Scott (Baylor University, Houston Texas). No one realized at that time the fruition of this relationship. These two giants, over the next two decades, would establish the fi eld of genitourinary prosthetics and clarify the diagnosis of erectile dysfunction. Working together, they would hold the majority of patents on the infl atable penile prosthesis and the artifi cial urinary sphincter. Although the initial concept of both of these devices arose from Dr. Scott, Dr. Furlow would do an integral portion of their modifi cations, holding patents on the modifi cation for use of the Keith needle to aid in placement of the penile cylinders, the development of the penile rear tip extenders, (enabling a reduction in inventory from 16-20 different penile prosthetic lengths to one basic size with adding length by the use of the rear stackable standardized extensions), the Furlow insertion tool for placement of the penile prosthesis, the development of secondary activation techniques, the moving of the AUS from the initial location with placement at the bladder neck to the bulbar urethra (Drs. Furlow and Barrett), development in techniques that would reduce infection rates of prosthetic devices to < 1%, the development of techniques to salvage infected prosthetic devises (Drs. Furlow and Barrett), and the description of urinary undiversion with use of simultaneous bladder augmentation and AUS placement (Drs. Barrett and Kramer). In addition to the outstanding innovations for IPP and AUS, Dr. Furlow worked with Dr. Scott to develop MMPI test for the differentiation of psychogenic versus organic erectile dysfunction and the development of the Nocturnal Penile Tumescence and Rigidity test. Together they lobbied the US government and insurance agencies to recognize organic erectile dysfunction as a medical diagnosis allowing for the coding and billing for the diagnosis and treatment of this disorder.

The development and fruition of prospective data bases: Olmsted County database, Prostate,

Renal and Bladder Cancer databases

There is no doubt that we stand on the shoulders of the giants who preceded us. The initial prospective database started at Mayo Clinic was by the Department of Medical Statistics and Epidemiology in 1974. This data base contains all medical records of individuals living in Olmsted County, Minnesota, with data acquired in a prospective fashion. Dr. Horst Zincke, observing the wealth of information found within the Olmsted county prospective data base, originated the concept of genitourinary-specifi c oncologic prospective databanks. Together with Dr. Fleming (Medical Statistics and Epidemiology) they began the prostate cancer prospective data base in 1985. Subsequently Dr. Blute, together with Dr. Leibovich, founded and maintained the renal cell cancer data base, and Dr. Blute, together with Dr. Frank, founded and maintained the bladder cancer data base beginning with both of these prospective data banks in 1994. Each data base has independent observers entering the data, and are associated with a urologist, pathologist, appropriate PhD scientist and statistician assigned to the project. Since these data bases were fi rst mined for information in 1982, they have led to > 300 peer-review and cited papers and numerous advances in the management of benign prostatic hyperplasia, prostate, renal and bladder cancer.

Pushing the horizons for surgical management of advanced prostate cancer

and renal cell carcinoma

Prostate CancerBy the early 1980s, Dr. Horst Zincke began to push the frontiers for the acceptable surgical management of prostate cancer. At that time most physicians considered advanced prostate cancer inoperable, and at the time of surgery if lymph node-positive disease was found, the procedure was abandoned and radiation therapy, hormonal therapy, or a combination of both were administered. Dr. Zincke, reviewing the Olmsted County data base in 1982, noted that if no more than two lymph nodes were involved with the disease process, and if radical prostatectomy was completed and postoperative hormonal therapy initiated, the 5-year survival of the patient population was 88%. This compared to comparable patient populations where the procedure was abandoned and either hormonal or radiotherapy given where the 5-year survival was 35%. Dr. Zincke’s fi nding sparked heated debate on the appropriate treatment of regional advanced prostate cancer.

Most institutions were wary of such aggressive treatment for limited metastatic prostate cancer and balked at the recommendations for completion of the radical prostatectomy and hormonal therapy as adjunct therapy. Although not universally accepted, Zincke’s statistics-based conclusions along with the documented excellent technical surgical results of Drs. Zincke and Robert Myers for patients undergoing radical prostatectomy, drew patients seeking hope for treatment of their cancer to the clinic. The outstanding work of Drs. Zincke and Myers established Mayo Clinic as one of the premier institutions for the treatment of prostate cancer.

Renal Cell CarcinomaDr. Reza Malek in 1972 reviewed pathologic fi ndings on patients undergoing nephrectomy for renal cell carcinoma at Mayo Clinic published on the fi ndings that the majority of the renal cell carcinomas then removed by nephrectomy could have been managed by partial nephrectomy. Dr. Malek subsequently recommended that partial nephrectomy should be the procedure of choice in the management of renal cell carcinomas. His concept was rapidly adopted by Dr. Horst Zincke, who chose to do partial nephrectomy on all renal cell cancer patients whenever technically possible. Although criticized for this approach at the time, the use of partial nephrectomy for the management of renal cell carcinoma at Mayo Clinic became the standard of care since 1980. Over the ensuing decades, controversy continues to surround this concept, and only with the accumulation of additional data will this debate that began in 1972 be answered.

Robotic Assisted Laparoscopic and Natural Orifi ce Surgical Techniques

(NOTES)

With the advent of robotic surgical techniques arising in the late 1990’s, the Department of Urology under Dr. Michael Blute, began pushing for the clinic to purchase the da Vinci robot. The clinic balked at the cost of the device and its unproven surgical benefi ts; subsequently the purchase of the robot was hung up in multiple Mayo Clinic committees. In 2002 Dr. Blute did an end run to the situation having a private donor give the money for the purchase of the robot and having the robot delivered to central receiving area. The clinic subsequently did not have much choice but to accept the situation. Dr. Blute then entrusted the development of robotic surgery to Dr. Matthew Gettman, who had just arrived on staff from a fellowship in endourology. Although faced with a daunting task, Dr. Gettman proved up to the challenge, and over the next several years numerous robotic or NOTES procedures were either fi rst performed at or refi ned at Mayo Clinic.

• Pyleoplasty (fi rst) using da Vinci robotic system – Dr. Gettman-2002

• Laparoscopic radical cystectomy with orthotopic ileal neobladder – Dr. Gettman-2005

• Robotic-assisted laparoscopic sacral colpopexy – Drs. DiMarco, Chow, Gettmann, Elliot-2004

• Robotic-assited partial nephrectomy – Dr. Gettman-2005• Evaluation of multiple hemostatic agents for management of

bleeding complications following laparoscopic and robotic surgery – Dr. Gettman-2005

• Initial experiences and outcomes on natural orifi ce translumenal endoscopic surgery in urology (NOTES) – Dr. Gettman-2005-2012

• Robotic-laparoscopic; ureterolysis for retroperitoneal fi brosis – Drs. Chow and Gettman-2010

Photovaporization of prostate

Dr. Reza Malek became enamored with the concept of how lasers could affect the practice of urology and began experimenting with their use and refi nement beginning in the early 1990’s. In 1998 Dr. Malek published the fi rst clinical outcomes of patients with BPH treated by photoselective vaporization of the prostate (PVP) using Greenlight laser. The subsequent refi nements in surgical techniques and his publication of the clinical long-term results using GreenLight PVP for BPH in 2000 eventually resulted in clearance of GreenLight PVP for treatment of BPH by the government in 2002. This technique subsequently became the predominant surgical method for treatment of BPH by 2004.

Treatment of Advanced Prostate Cancer

Mayo Clinic Division/Department of Urology has been a leader in research and treatment of prostate cancer since its inception. Its laboratories under the guidance of Dr. Don Tindall found that the blood protein HK-2 is diagnostic for prostate cancer. They were among the fi rst to clone the androgen receptor, develop immunohistochemical techniques for androgen receptor antibodies and evaluate their usefulness in normal and aberrant cellular growth. This research effort was greatly enhanced by the award of an NIH SPORE grant for prostate cancer research in 1992. Since this time numerous research fi ndings and clinical application for the treatment of advanced prostate carcinoma has come forth from the departmental laboratories that were greatly aided and enhanced by the collaborative efforts of the Departments of Biochemistry and Molecular Biology, Immunology, Medical Oncology and Pathology. Specifi cally, the discovery of two proteins, SKP-2 and FOX01 that allow androgen-dependent prostate cancer cells to survive in androgen-free environments – 2005. The development of and the clinical application for anti CTLA-4 monoclonal antibodies in clinically advanced prostatic cancer Drs. Thompson, Karnes, Frank, Blute, Kwon – 2008. The development of a specifi c clinic for the diagnosis and treatment of clinically advanced prostate cancer, Dr. Kwon – 2010. Based on clinical fi ndings from this clinic, Mayo became the fi rst facility to obtain FDA approval of C-11 Choline PET scan for detection of recurrent prostate cancer Departments of Urology, Pathology and Radiology (Dr. Kwon) – 2011.

Indeed, based largely on the success of the urology research efforts, Mayo Clinic (Rochester - Arizona and Florida) become the fi rst multicenter designated comprehensive cancer center by the NCI in 2002.

Innovations from the Department of Urology Mayo Clinic- Rochester

• First use of water as a medium for endoscopic evaluation of the bladder, replacing the use of air for cystoscopy – 1906

• Development of the Braasch cystoscope, the predominant cystoscopic instrument in use with minor modifi cations from 1910-1970

• Development of the Braash resectoscope, allowed resection of the prostate with direct endoscopic visualization, however did not provide for fulguration use limited from 1918-1926

• Development of the tunneled ureteral enteric re-implantation for a non-refl uxing anastomosis for urologic reconstruction primarily used for ureterosigmoidostomy – the Coffey-Mayo method – 1911

• Published fi rst comprehensive collection of genitourinary radiographic studies, Pyelography – Dr. Braasch – 1915

• Radio-opacity of 10% Sodium Iodine noted to result in visualization of the genitourinary tract, founding work for the development of radio-opaque contrast solutions – 1920-23.

• Development of the Braasch-Bumbus punch resectoscope – 1928

• Development of a endoscopic closed loop resectoscope; with temperature and pressure controlled irrigation system for prostate resection – 1928

• Popularized TURP as the defi nitive treatment for BPH compared to suprapubic prostatectomy – 1932-1947

• Defi ned the TUR syndrome – 1947

• Popularization of endoscopic surgery resulting in the recognition of urologists as the defi nitive surgeon for genitourinary system over general surgeons – 1947

• Development of the Culp –DeWeerd spiral fl ap pyeloplasty for UPJ obstruction – 1951

• Published ”Clinical Urology- An Atlas and Textbook of Roentgenologic Diagnosis” the classic textbook for genitourinary radiographic abnormalities from 1951-1985

• Culp hypospadias repair (release of penile chordee and tubularization of the urethral plate from the site of the hypospadias to the cornonal sulcus, the repair not carried into glans due to increased incidence of fi stula and stricture) – 1959

• Cecil-Culp repair of urethral strictures and urethral fi stulas following traumatic urethral injuries or failed hypospadias repairs – 1959

• Co-developed with Kodak for the process for nephrotomography 1960-1962

• Establishment of arguably the fi rst combined nephrology-urology center for the management and metabolic evaluation of urinary stone disease (Dr. Lynwood Smith) – 1967

• Modifi cation of the Braash cystoscope by Dr. Greene to provide fi ber-optic illumination, patented and marked by American Cystoscope Makers – 1970

• University Urologic Forum initiated by Drs. Furlow and Greene, this will eventually become the Society for University Urologists – 1972

• Co-development of the artifi cial urinary sphincter (AUS), and infl atable penile prosthesis (IPP) between Dr. Brantley Scott ( Baylor University) and Dr. Furlow (Mayo), Mayo was the second center to place both AUS and IPP and still holds patents on Furlow penile insertion tool to measure corpora internal diameter and length, IPP patent redesign to accommodate preloaded Keith needle for placement of IPP and rear tip extenders – 1970-1973

• Co-development with Baylor University and Mayo Clinic of MMPI testing and nocturnal penile detumense tests for accurate diagnosis of erectile dysfunction; this work will eventually be the basis used to have erectile dysfunction be recognized as a medical condition with appropriate diagnostic codes. 1970-1975

• Departments of Pathology and Urology establish and document the clinical usefulness of exfoliative urinary cytology in the practice of clinical urology – 1971-1979

• Mayo clinic surgeons (Drs. Malek and Zincke) become some of the fi rst surgeons to advocate for partial nephrectomy to replace total nephrectomy in all cases where this is possible – 1972

• Establishment of Olmsted County database: all medical records of individuals living in Olmsted County MN reviewed with prospective data base maintained will serve invaluable for the study of prostatic and renal disease in the future – 1974

• PP Kelalis, Lowel King and Barry Belman, publish the fi rst edition of “Clinical Pediatric Urology” the standard textbook for pediatric urology from 1976 to date

• Dr. Kelalis adopts and is the second individual to publish results with staged bladder reconstruction for bladder exstrophy- epispadias complex, following techniques described by Dr. R. Jeffs – 1978

• Dr. Kelalis named as the sole pediatric urologist to the National Wilms Tumor Study – 1979-1991

• Defi ned the clinical signifi cance of carcinoma in situ of bladder, Departments of Urology and Pathology – 1980

• Development of photodynamic therapy for carcinoma in situ- Drs. Farrow (Pathology) and Benson (Urology), although this was a prevalent way to treat CIS of the bladder in the 1980’s the advent of effect chemo and immunotherapy supplanted its usefulness. Department of Urology and Pathology – 1980

• Development of “Rapid” same day percutaneous nephrolithotomy: Drs. Segura, Patterson and LeRoy, Departments of Urology and Radiology, 1981-1000 cases performed in an 18-month time span from inception in 1981-1982.

• First to perform cavernosal reconstruction with graft material (Gortex) for reconstruction of the penis with Peyronie’s disease. – Dr. Furlow – 1983

• Discovery that intermittent UPJ obstruction can be unmasked by the use of Lasix, development of the diuretic IVP- 1983 (Dr. Malek) test later supplanted by use of diuretic renograms.

• Development of salvage procedures for infected AUS and IPP – Dr. Furlow

• Clarifi cation of the neuroanatomy of the prostate, prostatic apex and external sphincter, Dr. Myers (Urology and Dr. Cahill (Anatomy) – 1984

• Establishment of Dornier lithotripsy, one of fi rst 10 in the United States – 1985

• Development of fi rst prospective data base for prostate cancer, 1985 onward, (Note: retrospective data placed in databank from 1967-1985) – 1985 Dr. Zincke (Urology) and Dr. Fleming (Medical Statistics and Epidemiology)

• Refi nement of multiple ureteroscopic techniques and development and patenting of Segura stone basket- Drs. Segura and Patterson – 1987

• Described stone clearance rate for percutaneous nephrolithotomy was superior to ECSWL for stones > 2 cm, Drs. Segura, Patterson and Leroy – 1987

• Development of penile revascularization for erectile dysfunction using dorsal vein arterialization- Dr. Furlow – 1987

• Dr. Kelalis and Malizia document Tefl on, used as a injectable bulking agent for vesico-ureteral refl ux and urinary incontinence, has a dangerous migration problem (lungs, lymph nodes and brain) that may lead to signifi cant clinical side effects – 1989

• Initial papers presented on the incidence and progress of BPH in Olmsted County MN, fi rst of hundreds of epidemiology articles on urological and nephrologic diseases using this demographic database- Dr. Lieber – 1989

• Department of Urology Laboratories - One of the fi rst laboratories to clone the androgen receptor gene, develop immunohistochemical assays for the androgen receptor in fresh and pathologic tissues, investigate the modulation of androgen proteins in embryology, androgen responsive and nonresponsive tissues; Drs. Tindall, Young and Husmann – 1989 - to date

• NIH Sore Grant for Prostate Carcinoma Investigations; Dr Tindall – 1992-2012

• Refi nement in the management of renal cell carcinoma IVC thrombus that dropped the then mortality rate of 9% to 3%- Drs. Zincke and Blute – 1992

• Recommendation for age adjusted values for PSA – Dr. Osterling – 1993

• Establishment of prospective renal and bladder cancer databases, Dr. Blute – 1994

• Discovery that blood protein HK-2 is diagnostic for prostate cancer Drs. Tindall and Young – 1995

• Development of Photoselective vaporization of the prostate (PVP) using GreenLight laser for treatment of BPH with publication of fi rst pilot study of clinical outcomes Dr. Malek – 1998

• Publication that laser therapy for superfi cial squamous cell carcinoma of the penis provides 5-yr results equivalent to partial penectomy – resulting in validation of laser therapy for superfi cial squamous cell carcinoma of the penis- Dr. Malek – 1998

• Development of in-situ vaccination to activate T-cells against prostate cancer using CTLA-4 Dr. Kwon – 1999

• Publication of long-term results using GreenLight PVP for BPH Dr. Malek – 2000, studies eventually resulted in clearance of GreenLight PVP for treatment of BPH by the government in 2002 and become the predominant surgical method for treatment of BPH by 2004

• Mayo Clinic (Rochester - Arizona and Florida) become the fi rst multicenter designated comprehensive cancer center by NCI – 2002

• B7-H1 T-cell identifi ed as regulator for kidney cancer and that immune-regulation correlate with clinical outcomes Dr. Kwon – 2002

• Multiple fi rsts in robotic-assisted laparoscopic and natural orifi ce surgical techniques (NOTES) techniques – 2002-2012

- Pyleoplasty using da Vinci robotic system- Dr. Gettman – 2002

- Laparoscopic radical cystectomy with orthtopic ileal neobladder – Dr. Gettman-2005

- Robotic-assisted laparoscopic sacral colpopexy- Drs. DiMarco, Chow, Gettmann, Elliot – 2004

- Robotic-assisted partial nephrectomy- Dr. Gettman – 2005

- Evaluation of multiple hemostatic agents for management of bleeding complications following laparoscopic and robotic surgery – Dr. Gettman – 2005

- Initial experiences and outcomes on natural orifi ce translumenal endoscopic surgery in urology ( NOTES)- Dr. Gettman – 2005-2012

- Robotic-laproscopic; ureterolysis for retroperitoneal fi brosis- Drs. Chow and Gettman – 2010

• Initiation of studies evaluating simulation training on resident performance, multiple reports evaluating the affect of simulation training on resident performance – Dr. Gettman 2002- to date

• First center to demonstrate that intravesical chemo-instillation after transurethral resection of superfi cial bladder cancer reduces recurrence- Dr. Zincke – 2004

• Discovery of two proteins, SKP-2 and FOX01 that allow androgen-dependent prostate cancer cells to survive in androgen- free environments – Dr. Tindall – 2005 to date

• B7-H1 evaluation of methods, diagnosis and prognosis for treatment of multiple cancers: Combined efforts Department of Urology and Pathology): Dr Kwon – 2005 to date

• Clinical application of anti CTLA-4 monoclonal antibodies in clinically advanced prostatic cancer Drs. Thompson, Karnes, Frank, Blute, Kwon – 2008 to date

• Defi nition of Oncofetal protein IMP3 as a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinoma Dr. Kwon – 2008

• Development and evaluation of BioScore: Prognostic algorithm for renal cell carcinoma Drs. Boorjian, Kwon and Leibovich combined effort Departments of Urology and Pathology – 2009

• Use of inhibitors of B-7-CD28 co-stimulation in urologic malignancies – Dr. Kwon – 2009

• B-7-H1 expression, signifi cance and immunotherapeutic applications – Drs. Thompson, Cheville, Leibovich, Kwon, combined effort Departments of Urology and Pathology 2011 to date

• First facility to obtain FDA approval of C-11 Choline PET scan for detection of recurrent prostate cancer Departments of Urology, Pathology and Radiology – 2011

Compiled by D. A. Husmann