Nerve-sparing radical prostatectomy: A European discovery? Let’s take a look back in time
textbook. In March 1977, my wife and I attended an important international conference and the night before the meeting we went downtown to a restaurant. As we were about to sit down, I noticed an older man standing behind the maître d’ who looked very lonely. For the first and only time in my life, I went up to a total stranger and asked him if you would like to join us for dinner and why he was in town? It turned out that he was attending the same meeting and had been advised by the concierge, like us, to go to this same restaurant. His name was Pieter Donker, the Professor and Chairman of Urology at the University of Leiden in the Netherlands, whose specialty was neurourology. (Figure 1) After a wonderful dinner and conversation, I thought that was the end of it. But four years later, 4000 miles away we met again. He was now retired and I was invited by Udo Jonas, Donker’s successor, and my good friend Fritz Schroder to spend five days at the Boerhaave Surgical Congress in Leiden, operating, lecturing, and visiting laboratories. Finally, on my last day, Friday February 13, 1981, my 43rd birthday, my host told me that Dr. Donker appreciated my kindness a few years earlier and wanted to return the favour by taking me to see the windmill museum in Leiden. When I met Donker, I asked him what he was doing now that he was retired and learned that he was working in an anatomy laboratory. Without any premonition of what I was going to see, I asked to go there instead. In the laboratory, he took out a stillborn infant, a dissecting microscope, and his drawings. When I asked what he was doing, he said that he was dissecting out the nerves to the bladder. When I asked why, he said this it had never been done before, for the reasons I’ve given previously. When I asked about the location of the cavernous nerves, he said he had never looked. Three hours later, we located them outside the prostate. [4] Figure 2. From this observation, we knew where these microscopic nerves were located in a foetus. The trick was how to identify them in the adult male pelvis. It was like having the schematic to your television set and trying to find some tiny filamentous wires inside. I returned to Hopkins and once again used the operating room as an anatomy laboratory. While performing a radical prostatectomy in October1981, I noticed that the capsular arteries and veins of the prostate were located in the exact site where the nerves were present in our foetal dissections. I speculated that these vessels might provide the scaffolding for these microscopic nerves and that this neurovascular bundle could be used as the macroscopic landmark to identify them in the operating room. (Figure 3.) This observation fulfils the advice of Dr. Merrill Sosman, the Peter Bent Brigham radiologist “You only see what you look for and you recognise only what you know”. In March, 1982, Donker and I met again. He had performed more foetal dissections and microscopic step-section reconstructions that confirmed our original anatomical observation. I told him about my idea of the neurovascular bundle and he agreed with the suggestion. When I returned home, I performed a radical cystectomy on a 60-year-old man. I had never seen or heard of a patient who was potent after a cystectomy but on his 10th postoperative day he awoke with an erection! I now knew that we were on the right track. Using that technique, on April 26, 1982, I performed the first nerve-sparing radical prostatectomy on a 52-year-old man. He died 35 years following surgery, cancer free, having lived a normal life. To confirm our findings, we conducted further anatomical studies by removing en bloc the pelvic organs from a male cadaver that had been perfused with Bouin’s shortly after death, prepared 10,000 whole mount step sections, and performed a 3D reconstruction. This confirmed the constant association of the cavernous nerves with the capsular vessels to the prostate. [5] The final piece of the puzzle that remained was the fascia surrounding the prostate. Although everyone who performed prostatectomies was familiar with Denonvilliers’ fascia, little or nothing had been written about the layers of the lateral pelvic fashion. However, based upon a whole mount step-sectioned prostate that was harvested by Dr. Herbert Lepor (US) when he was a resident, it became clear that
Prof. Patrick Walsh James Buchannan Urological Institute Johns Hopkins Hospital (US)
pwalsh@jhmi.edu
The first operation for the cure of prostate cancer was performed via the perineal approach by Hugh Hampton Young at Johns Hopkins Hospital in 1904. In 1947, Terence Millin, an Irish urologist who worked in London, pioneered the retropubic approach. [1,2)] Although surgery proved effective in controlling cancer, it had substantial morbidity: impotence (90-100%), total incontinence (10-25%), and major bleeding, which was often life threatening when performed retropubically. For this reason, when treatment with external beam radiation began in the 1960s, surgery rapidly fell into disuse. In 1974, I arrived at Johns Hopkins Hospital to assume the position as the third director of the James Buchannan Urological Institute. When I arrived, I was surprised to learn that radical prostatectomies were rarely performed, even at the centre where it had been pioneered. Over the prior decade, I had trained at outstanding centres on the east and west coast but had never heard anyone suggest that these complications might be preventable. They were considered the price a patient paid for a chance at cure. At this time, I wondered what caused them and if it was possible to prevent them. As a successor of Hugh Young, I felt the personal responsibility to solve this problem. I began by looking into the anatomy of the dorsal vein complex and Santorini’s plexus and was surprised that had never been charted. Also, although the location of the cavernous nerves was not known, because all men were impotent, it was universally assumed that the nerves must run through the prostate. And only later did it become clear that men were incontinent because the location of the sphincter responsible for passive urinary control was not known. Why were we so ignorant? Because of limitations in using the adult cadaver. In the post mortem state, the abdominal contents compress the bladder and prostate into a thick pancake of tissue and formalin preservatives dissolve the fatty tissue planes making dissections impossible. So, I decided to use the operating room as an anatomy laboratory. Urologists were reluctant to operate because of the life threatening bleeding. So, this was the first problem I tackled. While performing radical cystectomies and the rare radical retropubic prostatectomy, I identified a common trunk of vessels over the urethra. This led to a technique that reduced blood loss dramatically, providing a safer and more thorough cancer operation. [3] Soon thereafter a patient came back to see me and told me that he was fully potent. How could that be? At that time everyone believed that because the nerves must run through the prostate, it would be impossible to preserve potency. But from this one patient I knew that was not true, but where were the nerves? The answer was not available in any
Figure 2. Optional: Dissection of left pelvic plexus in stillborn male. Bladder has been retracted to right. Peritoneum, pelvic vessels, pelvic fascia and pubic symphysis have been removed.
Figure 3. October,1981: author’s intraoperative drawing of the capsular vessels of the prostate that travelled in the same location as the cavernous nerves in the foetus.
the lateral pelvic fascia was divided into two layers, the prostatic fascia and levator fascia with the neurovascular bundle positioned between them and that if nerve sparing is properly performed, the prostatic fascia must remain on the prostate. Armed with this information, it also became possible to excise the neurovascular bundle thus providing wider margins of excision than ever before. This is why I called it an anatomic radical prostatectomy: nerve-sparing when possible; wide excision when necessary. Dr. Joseph Eggleston (US)., the director of surgical pathology, studied surgical specimens removed by the perineal, standard retropubic, and nerve-sparing approaches and concluded that nerve-preservation did not compromise the adequacy of the surgical margins. [6] Based on these discoveries, over the next decade radical prostatectomy became the most common form of treatment for localised prostate cancer in the U.S. In 1982, only 7% of men with prostate cancer underwent surgery. However, by 1992, with the availability of a safer procedure that had fewer side effects, and PSA screening to identify more men with curable disease, 70% of men ages 50-59 and 55% ages 60-69 underwent surgery and that year 100,000 operations were performed. A decade later, deaths from prostate cancer had declined by 33%, greater than for any other cancer in men or women over the same time. What would have happened without Pieter Donker’s contribution? In closing, this discovery would not have happened if: a patient had told me that he was potent following surgery and I had not listened and wondered why; and I had not invited an older, lonely man who was a total stranger to dinner; and I had not met him four years later 4000 miles away; and I had gone to the windmill museum and not asked to see what he was doing in retirement. If you asked Yogi Berra to explain how all this happened he would say that “it’s
too much of a coincidence to be coincidental”. If you asked Albert Einstein, he would say, “coincidence is God’s way of remaining anonymous”. And if you asked St. John Paul II, he would say that “in divine providence nothing is a coincidence”. That is what I believe. References: 1. Young HH: The early diagnosis and radical cure of carcinoma of the prostate: being a study of 40 cases and presentations of a radical operation which was carried out in 4 cases. Bull Johns Hopkins Hosp 1905; 16: 315. 2. Millin T: Retropubic Urinary Surgery. London: Livingston 1947. 3. Reiner WG and Walsh PC: An anatomical approach to the surgical management of the dorsal vein and Santorini’s plexus during radical retropubic surgery. J Urol 1979; 121: 198. 4. Walsh PC and Donker PJ: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982; 128: 492. 5. Lepor H, Gregerman M, Crosby R, Mostofi FK and Walsh PC: Precise localization of the autonomic nerves from the pelvic plexus to the corpora cavernosa: a detailed anatomical study of the adult male pelvis. J Urol 1985; 133: 207. 6. Walsh PC, Lepor H and Eggleston JC: Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 1983; 4: 473.
Friday, 10 March 11:00 – 11:15 7th International Congress on the History of Urology Yellow Area, Amber 7
Professor Pieter J. Donker 1914-1999
European Urology Today
46
February/March 2023
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