Functional Outcome and Complications following Ileal Neobladder Reconstruction in Male Patients without Tumor Recurrence. More than 35 Years of Experience from a Single Center.

PURPOSE: There is a lack of data on true long-term functional outcome of orthotopic bladder substitution. The primary study objective was to report our 35-year clinical experience. MATERIALS AND METHODS: Since October 1985, 259 male patients from a large single center radical cystectomy series with complete followup of more than 60 months (median 121, range 60-267) without recurrence, irradiation or undiversion that might have affected the functional outcome, were included. RESULTS: Median age at radical cystectomy and at survey was 63 (range 23-81) and 75 (range 43-92) years, respectively. Overall 87% of patients voided spontaneously and residual-free. This rate decreased with increasing age at the time of surgery (less than 50 years old 94%, 70 years old or older 82%). Overall day/nighttime continence rates were 90%/82%. These rates decreased with increasing age at the time of surgery from 100%/88% to 87%/80%. The overall pad-free rate was 71%/47%. Bicarbonate use decreased from 51% (5 years) to 19% (25 years). Patients with a followup of more than 20 years had the lowest rate of residual urine and clean intermittent catheterization (0.0%) as well as use of more than 1 pad at daytime/nighttime (6.3%/12.5%) and mucus obstruction (0.0%). Serum creatinine showed only the age related increase. The surgical complication rate was 27% and correlated inversely with functional results (chi-squared 11.227, p <0.005), even when the younger age at the time of surgery (younger than 60 years) was related to higher rates of surgical complications (chi-squared 6.80, p <0.05). CONCLUSIONS: The ileal neobladder represents an excellent long-term option for urinary diversion with an acceptable complication rate.

Unexpected Early Oncologic Mortality after Open Radical Cystectomy for Bladder Cancer: Who Is to Be Blamed?

PURPOSE: To investigate prevalence and variables associated with early oncologic mortality (EOM; within ≥30 to ≤90 days) of open radical cystectomy (RC) for bladder cancer. The unexpected rapidity of tumour recurrence and the huge metastatic burden of these patients drew us to analyse this cohort. METHODS: We reviewed our RC database. All 1,487 patients were treated with curative intent between January 1986 and December 2008. Imaging for staging was done by CT (chest) and CT or MRI (abdomen). Clinical and histopathological variables were recorded until death to determine whether disease- or treatment-related factors were associated with mortality. RESULTS: There were 93 deaths within 90 days of surgery. Twenty-four patients died from early progression to high volume disseminated metastatic disease. Group 1: unresectable tumours, which were never free of disease. Group 2: resectable tumours, considered tumour-free after RC. Group 1 is characterized by local tumour spread and a low distant failure rate. Group 2 has a low local and a high distant failure rate. CONCLUSIONS: Disease related (advanced tumour stage, positive soft tissue surgical margins (+STSM), non urothelial histology, unresectable tumours, atypical occult metastasis), rather than technical factors, had the leading role in EOM. Understaging was universal.

Update of the ICUD-SIU International Consultation on Bladder Cancer 2018: urinary diversion.

PURPOSE: To provide a comprehensive overview and update of the joint consultation of the International Consultation on Urological Diseases (ICUD) and Société Internationale d'Urologie on Bladder Cancer Urinary Diversion (UD). METHODS: A detailed analysis of the literature was conducted reporting on the different modalities of UD. For this updated publication, an exhaustive search was conducted in PubMed for recent relevant papers published between October 2013 and August 2018. Via this search, a total of 438 references were identified and 52 of them were finally eligible for analysis. An international, multidisciplinary expert committee evaluated and graded the data according to the Oxford System of Evidence-based Medicine. RESULTS: The incidence of early complications has been reported retrospectively in the range of 20-57%. Unfortunately, only a few randomized controlled studies exist within the field of UD. Consequently, almost all studies used in this report are of level 3-4 evidence including expert opinion based on "first principles" research. CONCLUSIONS: Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Complications can occur up to 20 years after surgery, emphasizing the need for lifelong follow-up. Progress has been made to prevent complications implementing robotic surgery and fast track protocols. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good results.

Development and validation of surgical training tool: cystectomy assessment and surgical evaluation (CASE) for robot-assisted radical cystectomy for men.

BACKGROUND: We aimed to develop a structured scoring tool: cystectomy assessment and surgical evaluation (CASE) that objectively measures and quantifies performance during robot-assisted radical cystectomy (RARC) for men. METHODS: A multinational 10-surgeon expert panel collaborated towards development and validation of CASE. The critical steps of RARC in men were deconstructed into nine key domains, each assessed by five anchors. Content validation was done utilizing the Delphi methodology. Each anchor was assessed in terms of context, score concordance, and clarity. The content validity index (CVI) was calculated for each aspect. A CVI ≥ 0.75 represented consensus, and this statement was removed from the next round. This process was repeated until consensus was achieved for all statements. CASE was used to assess de-identified videos of RARC to determine reliability and construct validity. Linearly weighted percent agreement was used to assess inter-rater reliability (IRR). A logit model for odds ratio (OR) was used to assess construct validation. RESULTS: The expert panel reached consensus on CASE after four rounds. The final eight domains of the CASE included: pelvic lymph node dissection, development of the peri-ureteral space, lateral pelvic space, anterior rectal space, control of the vascular pedicle, anterior vesical space, control of the dorsal venous complex, and apical dissection. IRR > 0.6 was achieved for all eight domains. Experts outperformed trainees across all domains. CONCLUSION: We developed and validated a reliable structured, procedure-specific tool for objective evaluation of surgical performance during RARC. CASE may help differentiate novice from expert performances.

Preoperatively Dilated Ureters are a Specific Risk Factor for the Development of Ureteroenteric Strictures after Open Radical Cystectomy and Ileal Neobladder.

PURPOSE: We evaluated preoperative ureteral obstruction as a risk factor for benign ureteroenteric anastomosis strictures in patients who underwent open radical cystectomy and ileal neobladder diversion. MATERIALS AND METHODS: A total of 953 patients in whom bilateral ileoureterostomy was performed between January 1986 and March 2009 formed the study population. A nonrefluxing Le Duc technique was applied in 357 consecutive patients and a refluxing Wallace type technique was applied in 596. We defined ureteroenteric anastomosis stricture as the need for specific therapy (eg stenting, dilatation or reimplantation) or as proven loss of renal function. Kaplan-Meier analysis was done to calculate the likelihood of ureteroenteric anastomosis stricture development. RESULTS: Median followup in the study population was 65 months. Preoperatively 109 patients had unilateral or bilateral obstructed ureters. Unilateral or bilateral obstruction developed in 107 of the 953 patients (127 reno-ureteral units, including 63 on the right side and 64 on the left side). Of the reno-ureteral units 98 had benign and 29 had malignant ureteroenteric anastomosis strictures. The overall stricture rate due to any cause in preoperatively obstructed ureters was 19.3% at 10 years vs 6.4% in preoperatively undilated ureters. For the refluxing Wallace type technique the 10-year ureteroenteric anastomosis stricture rate was 2.4% for preoperatively undilated and 7.6% for preoperatively obstructed ureters. For the nonrefluxing technique the corresponding rates at 10 years were 14.2% and 35.54%, respectively. CONCLUSIONS: Preoperatively obstructed ureters are at significantly higher risk for benign ureteroenteric anastomosis strictures during the postoperative course after ileal neobladder diversion. Most such Le Duc strictures are bilateral and most such Wallace type strictures are unilateral. The risk of ureteroenteric anastomosis stricture after ureteroenterostomy using the nonrefluxing technique is threefold the risk of the refluxing technique. There was no preponderance of left ureteroenteric anastomosis strictures after each technique.

Single Center Experience with Secondary Urinary Diversion after Initial Radical Cystectomy and Primary Urinary Diversion.

PURPOSE: We evaluate the risk of a second urinary diversion in patients after radical cystectomy and urinary diversion. MATERIALS AND METHODS: We retrospectively analyzed the records of 1,614 patients who underwent urinary diversion from January 1986 to March 2009. The primary diversion was neobladder in 71.9% of male patients and 42.3% of female patients, conduit in 17.6% and 38.6%, and ureterocutaneostomy in 9.5% and 12.5%, respectively. The outcome of interest was the need for a second urinary diversion. RESULTS: A total of 51 second/third diversions in 48 patients formed the study population. Mean time from primary to second diversion was 57 months (range 0 to 286). The indication for cystectomy was oncologic in 28 patients and nononcologic in 23. Conversions were continent to continent (14), incontinent to continent (14), continent to incontinent (13) and incontinent to incontinent (10). Twelve patients had tumor recurrence impacting the initial diversion. In 8 patients the indication was abscess necrosis of the diversion or radiogenic damage. Six patients with renal failure required conversion. All patients with conversion from incontinent to continent had a strong desire to avoid a stoma. Four patients died perioperatively and short bowel syndrome developed in 1 patient. CONCLUSIONS: A second urinary diversion was required in 1.8% of patients with bladder cancer with a heterogenous etiology vs 25% when the underlying disease was nononcologic. Only men with apex sparing cystectomy and women whose bladder had not been removed achieved excellent functional outcomes for later orthotopic reconstruction.

Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder.

PURPOSE: Oncofetal proteins are expressed in the developing embryo. Oncofetal protein expression correlates with the clinical outcome of nonmuscle invasive bladder urothelial carcinoma. IMP3, MAGE-A, glypican-3 and TPBG are oncofetal proteins that have not been well characterized in urothelial carcinoma of the bladder. MATERIALS AND METHODS: We investigated the expression of these 4 proteins and their association with clinical outcomes using tissue microarrays from 384 consecutive patients treated with radical cystectomy between 1988 and 2003 at 1 academic center. We stained for IMP3, MAGE-A, glypican-3 and TPBG. Univariable and multivariable Cox regression analyses were done to evaluate the association of oncofetal protein expression with disease recurrence and cancer specific mortality. RESULTS: IMP3, MAGE-A, glypican-3 and TPBG were expressed in 39.5%, 45%, 6% and 85% of urothelial bladder carcinomas, respectively. Expression was tumor specific and did not correlate with pathological features except for TPBG. At a median followup of 128 months 176 patients (46%) experienced disease recurrence, 175 (45.5%) had died of the disease and 96 (27.5%) had died of another cause. On univariable analysis IMP3 and MAGE-A expression was associated with an increased risk of disease recurrence (p <0.001 and 0.03) and cancer specific mortality (p = 0.004 and 0.03, respectively). On multivariable Cox regression analysis adjusted for the effects of standard clinicopathological features IMP3 and MAGE-A expression was independently associated with disease recurrence (p = 0.004, HR 1.55, 95% CI 1.15-2.11 and p = 0.02, HR 1.44, 95% CI 1.05-1.99, respectively) but not with cancer specific mortality. CONCLUSIONS: Oncofetal proteins are commonly and differentially expressed in urothelial carcinoma of the bladder compared to normal urothelium. IMP3 and MAGE-A expression was associated with disease recurrence and cancer specific mortality but glypican-3 and TPBG expression was not.

Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes.

CONTEXT: The urinary reconstructive options available after radical cystectomy (RC) for bladder cancer are discussed, as are the criteria for selection of the most appropriate diversion, and the outcomes and complications associated with different diversion options. OBJECTIVE: To critically review the peer-reviewed literature on the function and oncological outcomes, complications, and factors influencing choice of procedure with urinary diversion after RC for bladder carcinoma. EVIDENCE ACQUISITION: A Medline search was conducted to identify original articles, review articles, and editorials on urinary diversion in patients treated with RC. Searches were limited to the English language. Keywords included: 'bladder cancer', 'cystectomy', 'diversion', 'neobladder', and 'conduit'. The articles with the highest level of evidence were selected and reviewed, with the consensus of all of the authors of this paper. EVIDENCE SYNTHESIS: Both continent and incontinent diversions are available for urinary reconstruction after RC. In appropriately selected patients, an orthotopic neobladder permits the elimination of an external stoma and preservation of body image without compromising cancer control. However, the patient must be fully educated and committed to the labour-intensive rehabilitation process. He must also be able to perform self-catheterisation if necessary. When involvement of the urinary outflow tract by tumour prevents the use of an orthotopic neobladder, a continent cutaneous reservoir may still offer the opportunity for continence albeit one that requires obligate self-catheterisation. For patients who are not candidates for continent diversion, the ileal loop remains an acceptable and reliable option. CONCLUSIONS: Both continent and incontinent diversions are available for urinary reconstruction after RC. Orthotopic neobladders optimally preserve body image, while continent cutaneous diversions represent a reasonable alternative. Ileal conduits represent the fastest, easiest, least complication-prone, and most commonly performed urinary diversion.

The feasibility of ureteral tissue engineering using autologous veins: an orthotopic animal model with long term results.

BACKGROUND: In an earlier study we demonstrated the feasibility to create tissue engineered venous scaffolds in vitro and in vivo. In this study we investigated the use of tissue engineered constructs for ureteral replacement in a long term orthotopic minipig model. In many different projects well functional ureretal tissue was established using tissue engineering in animals with short-time follow up (12 weeks). Therefore urothelial cells were harvested from the bladder, cultured, expanded in vitro, labelled with fluorescence and seeded onto the autologous veins, which were harvested from animals during a second surgery. Three days after cell seeding the right ureter was replaced with the cell-seeded matrices in six animals, while further 6 animals received an unseeded vein for ureteral replacement. The animals were sacrificed 12, 24, and 48 weeks after implantation. Gross examination, intravenous pyelogram (IVP), H&E staining, Trichrome Masson's Staining, and immunohistochemistry with pancytokeratin AE1/AE3, smooth muscle alpha actin, and von Willebrand factor were performed in retrieved specimens. RESULTS: The IVP and gross examination demonstrated that no animals with tissue engineered ureters and all animals of the control group presented with hydronephrosis after 12 weeks. In the 24-week group, one tissue engineered and one unseeded vein revealed hydronephrosis. After 48 weeks all tissue engineered animals and none of the control group showed hydronephrosis on the treated side. Histochemistry and immunohistochemistry revealed a multilayer of urothelial cells attached to the seeded venous grafts. CONCLUSIONS: Venous grafts may be a potential source for ureteral reconstruction. The results of so far published ureteral tissue engineering projects reveal data up to 12 weeks after implantation. Even if the animal numbers of this study are small, there is an increasing rate of hydronephrosis revealing failure of ureteral tissue engineering with autologous matrices in time points longer than 3 months after implantation. Further investigations have to prove adequate clinical outcome and appropriate functional long-term results.

25 years of experience with 1,000 neobladders: long-term complications.

PURPOSE: We analyzed the long-term complications (greater than 90 days postoperatively) in a large, single center series of patients who underwent cystectomy and substitution with an ileal neobladder. MATERIALS AND METHODS: A total of 1,540 radical cystectomies were performed at our center between January 1986 and September 2008. Of the patients 1,013 received an ileal neobladder. Only the 923 patients with followup longer than 90 days (median 72 months, range 3 to 267) were included in analysis. All long-term complications were identified. The complication rate was calculated using the Kaplan-Meier method. RESULTS: The overall survival rate was 65.5%, 49.8% and 28.3% at 5, 10 and 20 years, respectively. The overall long-term complication rate was 40.8% with 3 neobladder related deaths. Hydronephrosis, incisional hernia, ileus or small bowel obstruction and feverish urinary tract infection were observed in 16.9%, 6.4%, 3.6% and 5.7% of patients, respectively, 20 years postoperatively. Subneovesical obstruction in 3.1% of cases was due to local tumor recurrence in 1.1%, neovesicourethral anastomotic stricture in 1.2% and urethral stricture in 0.9%. Chronic diarrhea was noted in 9 patients. Vitamin B12 was substituted in 2 patients. Episodes of severe metabolic acidosis occurred in 11 patients and 307 of 923 required long-term bicarbonate substitution. Rare complications included cutaneous neobladder fistulas in 2 cases, and intestinal neobladder fistulas, iatrogenic neobladder perforation, spontaneous perforation and necrotizing pyocystis in 1 each. CONCLUSIONS: Even in experienced hands the long-term complication rate of radical cystectomy and neobladder formation are not negligible. Most complications are diversion related. The challenge of optimum care for these elderly patients with comorbidities is best mastered at high volume hospitals by high volume surgeons.