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.

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.

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.

Lessons learned from 1,000 neobladders: the 90-day complication rate.

PURPOSE: We report the 90-day morbidity of the ileal neobladder in a large, contemporary, homogenous series of patients who underwent radical cystectomy at a tertiary academic referral center using a standard approach. MATERIALS AND METHODS: Between January 1986 and September 2008 we performed 1,540 radical cystectomies. A total of 281 patients had an absolute contraindication for orthotopic reconstruction. The remaining 1,259 patients were candidates for a neobladder. Of these patients 1,013 (66%) finally received a neobladder and form the basis of this report. All patients had a thorough followup until December 2008 or until death. All complications within 90 days of surgery were defined, categorized and classified by an established 5 grade and 11 domain modification of the original Clavien system. RESULTS: Of 1,013 patients 587 (58%) experienced at least 1 complication within 90 days of surgery. Infectious complications were most common (24%) followed by genitourinary (17%), gastrointestinal (15%) and wound related complications (9%). The 90-day mortality rate was 2.3%. Of the patients 36% had minor (grade 1 to 2) and 22% had major (grade 3 to 5) complications. On univariate analysis the incidence and severity of the 90-day complications rate correlate highly significantly with age, tumor stage, American Society of Anesthesiologists score and preoperative comorbidity. CONCLUSIONS: Radical cystectomy and ileal neobladder formation represent a major surgery with potential relevant early complications even in the most experienced hands. The rate of severe and lethal complications is acceptably low.

Oncological followup after radical cystectomy for bladder cancer-is there any benefit?

PURPOSE: Tumor recurrence after radical cystectomy for bladder cancer can be detected in an asymptomatic patient by regular followup or in a symptomatic patient by symptom guided examination. To our knowledge it is still unknown whether detecting tumor recurrence at an asymptomatic stage offers a better survival rate. MATERIALS AND METHODS: A total of 1,270 radical cystectomies for bladder cancer were performed at a single institution between January 1, 1986 and December 2006. All patients had regular followup examinations with chest x-ray and abdominal ultrasound every 3 months, computerized tomography of the abdomen every 6 months, and bone scan and excretory urography every 12 months. Additional examinations were required for symptomatic disease. We analyzed the first site and date of tumor recurrence. Survival was compared using the log rank test. RESULTS: The 20-year recurrence rate was 48.6% in the complete series. Tumor recurrence developed in 444 patients, including 154 asymptomatic and 290 symptomatic patients, with a mean time after radical cystectomy of 20 and 17.5 months, respectively. The most frequent symptoms were pain, ileus, acute urinary retention, hydronephrosis with flank pain, hematuria, neurological symptoms and a palpable mass. Of the 444 patients 182 (41%) had local recurrence and 324 (73%) had distant failure at the time of first recurrence. The overall survival rate 1, 2 and 5 years after first recurrence was 22.5%, 10.1% and 5.5% in asymptomatic patients, and 18.9%, 8.2% and 2.9% in symptomatic patients, respectively (log rank not significant). CONCLUSIONS: This study fails to demonstrate a survival benefit for detecting tumor recurrence early at an asymptomatic stage by regular followup examinations. These data show that symptom guided followup examinations may provide similar results at lower cost.

Upper urinary tract recurrence after radical cystectomy for bladder cancer--who is at risk?

PURPOSE: Patients who underwent radical cystectomy for bladder cancer are at risk for upper urinary tract recurrence. We identified subgroups of patients at increased risk for upper urinary tract recurrence. MATERIALS AND METHODS: All 1,420 patients who underwent radical cystectomy for bladder cancer at our center between January 1986 and October 2008 were included in the study. Negative frozen sections of the ureteral margins were obtained from all patients. Data analysis included preoperative tumor history, pathological findings of the cystectomy specimen and complete followup. Survival was calculated using the Kaplan-Meier method. RESULTS: Until October 2008, 25 cases of upper urinary tract recurrence were observed. The overall rate of upper urinary tract recurrence at 5, 10 and 15 years was 2.4%, 3.9% and 4.9%, respectively. Of the patients 3 had superficial tumors of the renal pelvis and 22 had invasive upper tract transitional cell carcinoma. Upper urinary tract recurrence did not develop in any patients with nontransitional cell carcinoma. Four risk factors for upper urinary tract recurrence were identified including history of carcinoma in situ (RR 2.3), history of recurrent bladder cancer (RR 2.6), cystectomy for nonmuscle invasive bladder cancer (RR 3.8) and tumor involvement of the distal ureter in the cystectomy specimen (RR 2.7). Patients with transitional cell carcinoma who had none of these risk factors had an upper urinary tract recurrence rate of only 0.8% at 15 years. This rate increased with the number of positive risk factors, ie 8.4% in patients with 1 to 2 risk factors and 13.5% in those with 3 to 4 risk factors. CONCLUSIONS: Patients who underwent cystectomy for transitional cell carcinoma and with at least 1 risk factor for upper urinary tract recurrence should have closer followup regimens than those with nontransitional cell carcinoma or without any of these risk factors.

Quantification of the survival benefit of early versus deferred cystectomy in high-risk non-muscle invasive bladder cancer (T1 G3).

OBJECTIVES: To review understaging and survival of patients who underwent early versus deferred radical cystectomy (RCX) for high-risk non-muscle invasive bladder cancer (NMIBC; T1 G3). METHODS: The results of 1,521 RCXs including 1,420 for bladder cancer were reviewed: (1) A total of 114 patients with high-risk NMIBC underwent a single TUR-BT followed by immediate RCX to estimate the understaging rate. (2) As much as 260 patients with NMIBC had long-term follow-up before RCX to determine the upgrading and upstaging over time. (3) We compared survival in patients with initial T1 G3 bladder cancer (BC) treated with early RCX (n = 175) versus deferred RCX (n = 99) for recurrent T1 G3. RESULTS: (1) Our understaging rate was 20.2%. (2) Allowing NMIBC to upgrade portents a 19% survival disadvantage. (3) The 10 years cancer-specific survival rate was 78.7% in early and 64.5% in deferred RCX. CONCLUSIONS: Early, as compared to deferred RCX, has a distinct survival advantage for high-risk NMIBC. Patients should be counselled accordingly.