AUA Summit - The Pioneering and Diverse Contributions of Leonard N. Zinman, M.D. to Urology
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  4. Issue 7 - Fall 2021
  5. Leonard N Zinman

The Pioneering and Diverse Contributions of Leonard N. Zinman, M.D. to Urology

Leonard N. Zinman, MD completed his medical degree at Tufts University School of Medicine; his urologic residency training at the University of California San Francisco, the Tufts University surgical division at the Boston Veterans Affairs Medical Center, and the Massachusetts General Hospital; and his fellowship training the University College London Hospital’s Institute of Urology and the Great Ormond Street Hospital for Sick Children with formative mentorship from Drs. Charles G. Child III, Wyland F. Leadbetter, W. Hardy Hendren III, Richard Turner-Warwick, David Innes Williams, and John Blandy.

Zinman was then recruited to the Lahey Clinic where he spent the remainder of his career and served as Chairman of the Department of Urology from 1986 to 1993. Zinman served as President of the New England American Urologic Association (NE-AUA) from 1991 to 1992, and was a founding member of the Society of Genitourinary Reconstructive Surgeons (GURS) for which he served as President from 1996 to 1997. In recognition of his many valuable contributions to Urology, Zinman was inducted as an honorary fellow into the Royal College of Surgeons in 2011, and was awarded Lifetime Achievement Awards by the AUA in 2015 and GURS in 2019. We chronicle Zinman’s impact on Urology by focusing on his contributions that have altered surgical practice.

Kidney

Surgical Treatment of Renal Malignancies

Zinman persistently evaluated the optimal surgical management of renal cell carcinoma (RCC). He championed the use of partial nephrectomy in patients with contraindications to radical nephrectomy in 1967, long before nephron-sparing surgery became the gold standard treatment for small renal masses.1

In 1987, Zinman challenged the existing Robson staging system2 for RCC with venous extension. His experience operating on 44 patients with RCC and caval thrombus extension highlighted discordance between the Robson staging system and clinical outcomes. With John Libertino, MD, Zinman found that Robson Stage IIIa disease without nodal or perinephric spread demonstrated similar survival to Stage I patients after resection.3 Subsequently, Zinman challenged the utility of cytoreductive nephrectomy in locally advanced and metastatic disease. His work laid the foundation for the ongoing debate about the role of cytoreductive nephrectomy in the age of novel systemic therapies.4

In a 1990 collaboration, Zinman applied total hypothermic circulatory arrest to the surgical management of RCC with tumor thrombus. The technique demonstrated low morbidity and mortality leading to improved surgical outcomes in these patients.5

Sugrical Treatment of Renovascular Disease

Zinman and Libertino described the first viable alternative to the aortorenal bypass for patients with renovascular hypertension (RVH). The hepatorenal bypass successfully revascularized patients with RVH who had contraindications to aortorenal bypass such as prior aortic repairs, severe atherosclerosis, or complete aortic thrombosis. In a small case series, post-operative angiograms demonstrated excellent renal revascularization without compromise of hepatic circulation.

Zinman and Libertino further broadened their work on revascularization for RVH by demonstrating therapeutic benefit of bypass in patients with chronic renal artery occlusion as an alternative to simple nephrectomy. In 1977, Zinman published a series of 9 patients who experienced resolution of RVH and improved renal function after renal artery revascularization.8 The revascularization approach pioneered by Zinman opened the door for modern endovascular procedures that are now the gold standard of RVH management.9

As the treatment options for RVH expanded, Zinman devised new methodology to identify candidates for revascularization by analyzing two renin-based tools to predict the probability of improvement or cure following revascularization: the Divided Renal Vein Renin Ratio and the Vaughan Scoring System.10 In a collaboration, Zinman helped demonstrate that 35% and 48% of patients who were predicted to have ‘incurable’ disease by the Divided Renal Vein Renin Ratio and Vaughan Scoring System, respectively, could benefit from surgical intervention11 Until the late 1980s, revascularization procedures had been utilized primarily in younger patients with RVH secondary to mural dysplasia. Zinman and Libertino expanded the indications by demonstrating improvement or cure of RVH at one year follow up in 95.7% of patients with a mean age of 49.5 years most of whom were affected by atherosclerotic disease12

Ureter

Ureteral Reimplantation During Renal Transplantation

In 1978, Zinman and Libertino described a modified Politano-Leadbetter technique for the creation of an anti-refluxing ureteroneocystostomy in transplant patients13 Zinman reported no major urologic complications in his cohort of 95 patients receiving 100 renal allografts. Previous reports documented urologic complication rates up to 24%, including events such as urinary extravasation, fistula formation, ureterovesical anastomotic disruption, ureteral sloughing, ureterovesical obstruction and kidney loss. Zinman and Libertino attributed the reduced complications to the novel tunneling technique, which eliminated the need for a second incision when creating the detrusor hiatus thereby decreasing potential damage to the submucosal tunnel.14

Bladder

Cecum Use in Augmentation Cystoplasty

In the 1970s, Zinman and Libertino proposed the cecum as a viable augmentation alternative to ileum or sigmoid colon. In a 1980 report on 34 cecocystoplasties, they reported an 8.8% complication rate with 2 patients requiring surgical closure of sinus tracts and 1 patient requiring incisional hernia repair16 Although ileocystoplasty remains the most widely used technique, alternative bowel segments, such as cecum, have proven valuable in specific cases including reoperative and previously radiated fields17

Ileocecal Conduit for Urinary Diversion

Concern was raised regarding the ability of the low-pressure ileal conduit to resolve pre-existing hydronephrosis, prevent upper tract deterioration, and stabilize the incidence of stone disease and pyelonephritis.19,20 Zinman and Libertino developed a novel technique inspired by the Nissen fundoplication to address these concerns. In 1986, they reported on 38 patients who had undergone creation of a conduit with a competent ileocecal sphincter. This technique effectively prevented reflux and created a competent ileocecal valve in 94.7% of patients evaluated by retrograde cecography. At long-term follow-up up to 9 years, resolution of pre-existing hydronephrosis and preservation of normal upper tracts were demonstrated.21-23

Acknowledging the benefit of the ileocecal sphincter, Zinman and Libertino proposed augmenting pre-existing ileal conduits through the addition of an ileocecal loop, leaving the original ureteroileal anastomosis intact and converting the pre-existing stoma into a colonic conduit. Given the high complication rates of ileal conduits reported in contemporary studies,24 the add-on ileocecal loop served as a valuable intervention to prevent reflux and subsequent upper tract deterioration due to ascending urinary tract infections and discoordinate ureteroileal peristalsis.25

Urethra

Mitomycin C For Refractory Bladder Neck Contractures (BNCs)

Recurrent BNCs often require repeated endoscopic treatments or advanced bladder neck reconstruction. In 2011 Dr. Zinman introduced injection of mitomycin C into the endoscopic urethrotomy sites for the treatment of recurrent BNCs. Urethrotomy with injection of mitomycin C was demonstrated to have improved durability compared to urethrotomy alone.37

Urethral Stricture Repair

Beginning in 1997, Zinman described the use of extragenital flaps, such as muscle-assisted skin grafts, prefabricated muscle skin composites, and pudendal fasciocutaneous medial thigh flaps for high-risk urethral strictures.26 Zinman also published extensively on the use of myocutaneous flaps in refractory bulbomembranous and panurethral strictures.26 With Allen Morey, MD, Zinman developed the Q-flap technique, a modified McAninch flap incorporating a midline ventral longitudinal penile extension for panurethral stricture reconstruction in 2000. The Q-flap was the longest vascularized skin pedicle flap utilized in a single stage repair, reducing the need for tissue grafting.27

In 2015, Zinman and Alex J. Vanni, MD expanded the options for patients at high risk of graft failure with the first description of a combined buccal mucosal graft (BMG) and gracilis muscle flap. They demonstrated that BMG urethroplasty with a gracilis muscle flap at the graft bed was a feasible and effective option in a series of 20 patients with a history of radiation or refractory stricture disease. Urethral reconstruction was successful in 80% of patients at a mean follow-up of 40 months.28

Beyond the use of BMG, Zinman also worked with Vanni to repurpose transanal endoscopic microsurgery (TEM) to harvest rectal grafts. In lengthy urethral strictures where oral mucosa grafts and fasciocutaneous flaps are unavailable or contraindicated, rectal mucosa is an effective alternative. Previous techniques required bowel resection, which risked ileus, adhesions, and bowel obstruction. Zinman and Vanni were the first to publish their success in applying the TEM technique, originally developed to resect rectal masses, to the procurement of rectal mucosal grafts. In a 2016 study of4 patients, 1 patient experience stricture recurrence and no colorectal complications were reported.29-30

Zinman introduced a novel technique for removal of Urolume stents in which segmental urethrectomy was avoided through urethral mobilization, dorsal urethrotomy to remove the individual metal tines of the stent, and augmented urethroplasty with a dorsal buccal graft onlay.31 In 2012, Zinman and Jill Buckley, MD retrospectively studied 12 patients who underwent the aforementioned procedure and avoided en bloc removal. Urethral preservation was possible in all cases and 83% of the patients were stricture-free at a median follow-up of 4 years. One patient required a suprapubic catheter following treatment failure and one patient required repeat urethroplasty at 7 years of follow-up.32

Urethral Fistula Repair

In 2003, Zinman demonstrated the successful transperineal repair of rectourethral fistulas (RUFs) with the interposition of a gracilis muscle flap supporting a skin or buccal mucosal graft in 22 patients. This technique represented a viable alternative to the available treatments, which included temporary colonic diversion, rectal pull-through with transperineal primary closure or a York-Mason procedure.33 In 2010, Zinman, Buckley, and Vanni published a study on a cohort of 74 patients who underwent transperineal RUF repair with muscle interposition flaps and selective use of buccal mucosal grafts. By improving buccal mucosal graft take, separating suture lines, and filling the void exposed by dissection of the plane between the rectum, urethra, prostate, and bladder, the gracilis muscle flap was demonstrated to be a reliable component of complex RUF repair.34 In 2016, Zinman and Vanni published a study of the outcomes of this approach 98 patients. At median follow-up of 14.5 months, 90 of 98 patients experienced successful RUF closure after one procedure. The overall 30-day and 90-day complications rates were 29% and 13%, respectively.35

Zinman and Vanni also developed a novel organ-sparing approach for reconstruction of radiation-induced prostato-symphyseal fistulas (PSFs). In 2016, a series of 4 patients who underwent pubic symphysis debridement, fistula closure, and placement of an interposition rectus abdominis muscle flap demonstrated fistula resolution after one repair in each patient at a median follow-up of 27 months. One patient later required permanent urinary diversion secondary to intractable radiation cystitis.36 This approach can avoid permanent urinary diversion and tenuous bladder neck reconstruction in PSF patients and is associated with minimal short-term complications.

Nigro Protocol for Urethral Squamous Cell Carcinoma

The Nigro protocol, originally developed to treat anal squamous cell carcinoma, utilizes systemic 5-fluorouracil and mitomycin combined with local radiation38 Zinman pioneered the application of the Nigro protocol to treat urethral squamous cell carcinoma, which alternatively is treated with extirpative surgery and urinary diversion or radiation therapy. In a cohort of 26 patients who underwent combined chemoradiation, 79% of patients showed a complete response. The 5-year overall, disease-specific, and disease-free survival rates were 52%, 68.4%, and 43.2%, respectively. Comparatively, 5-year survival rates for surgery or radiation therapy alone were reported to be 0-38% and 0-25%, respectively. The transition from extirpative surgery with urinary diversion to a genital-preserving alternative without compromising oncologic outcomes revolutionized management of this disease.39

Founding of the Society for Genitourinary Reconstructive Surgery

Zinman recognized the need for a dedicated professional society to share insights, advance the academic discipline, and recruit trainees to reconstructive urology. With Drs. Charles J. Devine Jr, Charles E. Horton Sr., and Gerald H. Jordan, Zinman helped to convene the first multidisciplinary meeting of genitourinary reconstructive surgeons in 1986 and co-founded the Society of Genitourinary Reconstructive Surgeons (GURS). Zinman and Libertino co-edited the first textbook in genitourinary reconstructive surgery. Zinman remained an active member of GURS since its inception and served as GURS President from 1996 to 1997.40

Conclusion

Zinman’s landmark contributions include advancing surgical management of RCC, developing novel interventions for RVH, refining urinary diversion techniques, pioneering multimodal chemoradiation for urethral squamous cell carcinoma, introducing intralesional injection of mitomycin C for refractory bladder neck contracture, applying advanced flap and graft techniques complex urinary fistula and urethral stricture disease, and co-founding the Society of Genitourinary Reconstructive Surgeons. As a master reconstructive urologist, a visionary who introduced practice-altering advancements, and a mentor to generations of trainees, Leonard N. Zinman, MD will be remembered as one of the most significant contributors to the field of Urology.

Authors

Jamie A. Cavallo, MD, MPHS

Alex Vanni, MD

References

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  37. Nagpal K, Zinman LN, Lebeis C. Durable results of injection of mitomycin C with internal urethrotomy for refractory bladder neck contractures: multi-institutional experience. Urol Pract 2015; 2: 250. Editor Comment. Published online 2015.
  38. Nigro, N. D., Seydel, H. G., Considine, B., Vaitkevicius, V. K., Leichman, L. and Kinzie, J. J.: Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer, 51: 1826, 1983.
  39. Kent M, Zinman L, Girshovich L, Sands J, Vanni A. Combined chemoradiation as primary treatment for invasive male urethral cancer. J Urol. 2015;193(2):532-537. doi:10.1016/j.juro.2014.07.105
  40. Members of the GURS Board of Directors Since 1996. Society of Genitourinary Reconstructive Surgeons Archives. Current as of June 1, 2014. Accessed on June 5, 2020. Managed by Veritas Association Management. East Dundee, IL 60118