Delayed Ureterectomy after Incomplete Nephroureterectomy for Upper Tract Urothelial Carcinoma: Pathologic Findings and Outcomes

Objectives To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks. .

Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.

PURPOSE: A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months. MATERIALS AND METHODS: A total of 17 patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment were enrolled in the study. A single treatment of rAd-IFNα (3 × 10(9) to 3 × 10(11) particles per ml) formulated with the excipient Syn3 was administered. Patient safety was evaluated for 12 or more weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months. RESULTS: Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity was encountered. Urgency was the most common adverse event and all cases were grade 1 or 2. rAd-IFNα DNA was not detected in the blood. However, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses of 10(10) or more particles per ml with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease-free at 29.0 and 39.2 months, respectively. CONCLUSIONS: Intravesical rAd-IFNα/Syn3 was well tolerated with no dose limiting toxicity encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in nonmuscle invasive bladder cancer recurring after bacillus Calmette-Guérin.

Delayed ureterectomy after incomplete nephroureterectomy for upper tract urothelial carcinoma: pathologic findings and outcomes.

OBJECTIVES: To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. MATERIALS AND METHODS: After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. RESULTS: From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. CONCLUSIONS: Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks.

Penoscrotal extramammary Paget's disease: the University of Texas M. D. Anderson Cancer Center contemporary experience.

PURPOSE: Extramammary Paget's disease is a rare intra-epithelial malignancy that is occasionally associated with an invasive adenocarcinoma component as well as other secondary cancers. We investigated a consecutive series of patients referred for extramammary Paget's disease of the penis or scrotum at a single center in the contemporary era to determine the presence of secondary cancers and treatment outcomes. MATERIALS AND METHODS: Between December 1990 and February 2009, 20 patients with extramammary Paget's disease of the scrotum and/or penis were seen. Patients were investigated with computerized tomography of the abdomen/pelvis, chest x-ray, cystoscopy, colonoscopy and serum prostate specific antigen measurement to rule out obvious secondary cancer. Clinical charts were reviewed with institutional review board approval. Mean followup of treated cases was 48 months (range 7 to 208). RESULTS: Patients were 50 to 86 years old with a history of symptoms of between 6 months and 10 years. Eight patients had invasive adenocarcinoma, of whom 2 died of the disease and 3 who had disease at 5, 7 and 40 months, respectively, were undergoing multimodal therapy. No patient with confirmed intra-epidermal disease only died of the disease. Invasive disease predicted nodal and metastatic progression. CONCLUSIONS: Surgical resection to achieve tumor-free margins resulted in durable relapse-free survival of patients with intra-epidermal extramammary Paget's disease alone. Extramammary Paget's disease with invasion was associated with regional metastatic progression. The latter scenario as well as failure to treat localized extramammary Paget's disease alone was associated with a fatal outcome. Systemic chemotherapy should be further explored in patients with invasive adenocarcinoma or lymph node positive disease.

Age and body mass index are independent risk factors for the development of postoperative paralytic ileus after radical cystectomy.

OBJECTIVES: To identify the risk factors that would aid in the identification of patients at the greatest risk of developing postoperative paralytic ileus (POI). POI is a common complication after radical cystectomy and can result in a prolonged hospital stay and delayed recovery. METHODS: A retrospective cohort study design was used to analyze data from consecutive patients presenting to our institution for radical cystectomy with pelvic nodal dissection. POI was declared if patients were without evidence of bowel function beyond the anticipated discharge goal of 6 days. The association between several clinical features and the occurrence of POI was examined. RESULTS: Of 283 patients, 43 (15.2%) developed POI. Of the 43 patients, 38 (88.4%) were given total parenteral nutrition for nutritional supplementation. No difference in the incidence of POI was observed between the sexes, previous abdominal operations, estimated blood loss, transfusion requirement, operative time, neoadjuvant chemotherapy, or previous radiotherapy. POI was observed in 11.3% of normal and overweight patients (body mass index [BMI] <30.0 kg/m(2)) compared with 25.6% of obese patients (BMI ≥30.0 kg/m(2); P = .005). On multivariate analysis adjusted for the influence of competing variables, increasing age (hazard ratio 1.09, 95% confidence interval 1.02-1.16, P = .008) and BMI (hazard ratio 1.09, 95% confidence interval 1.03-1.17, P = .007) were significantly associated with the presence of POI. CONCLUSIONS: Our results showed that increasing age and BMI were significantly associated with the presence of POI in patients undergoing radical cystectomy for bladder cancer.

Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria.

PURPOSE: Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations. MATERIALS AND METHODS: We retrospectively reviewed consecutive radical cystectomies done for urothelial bladder carcinoma at our institution between January 2004 and September 2006. Adverse events within 90 days postoperatively were recorded. We explored the association of important risk factors with the overall complication rate and specific complications. RESULTS: A total of 283 patients were included in the study. Complete 90-day followup data were available on 90% of patients. Median age was 70 years (IQR 62-75). Median body mass index was 26.8 kg/m(2) (IQR 24.4-31.0). At least 1 adverse event was observed in 152 patients (54.0%) and a grade 3-4 adverse event was observed in 40.3%. The most common grade 4 adverse events were myocardial infarction in 3.5% of cases, septic shock in 2.8% and pulmonary embolism in 1.8%. No patient died during followup. An association between body mass index, and any and major adverse events was found after adjusting for confounding variables. CONCLUSIONS: More than 50% of patients experience an adverse event after radical cystectomy and 40% are major. Body mass index is independently associated with adverse events in these patients. These findings are important for individualized risk assessment, patient counseling and uniform assessment of quality care.

Cardiac history and risk of post-cystectomy cardiac complications.

OBJECTIVES: To evaluate risk factors for postoperative cardiac complications (POCC). Patients undergoing cystectomy often have significant baseline cardiac disease. Despite preoperative medical optimization, postoperative cardiac complications remain a significant source of morbidity. METHODS: A retrospective review of all radical cystectomies for bladder cancer between January 2004 and September 2006 was performed. Twelve preoperative risk factors were evaluated, including age, Charlson Comorbidity Index, type of urinary diversion, and previous cardiac history. All complications, including myocardial infarction (MI) and new onset arrhythmia, were recorded for 90 days postoperatively. Univariate and multivariate analysis were performed. RESULTS: A total of 283 patients underwent cystectomy for bladder cancer between January/2004 and September 2006. The median age of the cohort was 70 (35-90) years. Of 283 patients, 64 (23%) had a significant preoperative cardiac history, including 18 (6%) with prior coronary artery bypass and 30 (11%) with a history of MIs. Thirty-one (11%) patients had either new onset arrhythmia (22, 8%) or MI (10, 4%) and 1 had both. On univariate analysis, cardiac history, age, type of urinary diversion, and the Charlson Comorbidity Index demonstrated significance. The risk of POCC was associated with ileal conduit urinary diversion (P = .026, OR 5.58 [1.23-25.36]) and the Charlson Index score (P = .030, OR 1.28 [1.024-1.60]) on multivariate analysis. CONCLUSIONS: Multiple, inter-related factors may predict cardiac complications in the early postoperative period. Despite perioperative optimization, patients with a prior cardiac history should be counseled, regarding the increased risk of postoperative cardiac complications. The association between cardiac complications and ileal conduit diversion highlights the selection bias toward patients with preexisting comorbid disease.

Is vascular endothelial growth factor modulation a predictor of the therapeutic efficacy of gefitinib for bladder cancer?

PURPOSE: The epidermal growth factor receptor inhibitor gefitinib (Iressa) is currently being studied in patients with bladder cancer and it has significant anti-angiogenic activity. We investigated the relationship between the modulation of vascular endothelial growth factor (Santa Cruz Biotechnology, Santa Cruz, California) expression and the biological efficacy of gefitinib for bladder cancer. MATERIALS AND METHODS: In vitro the 4 bladder cancer cell lines 253JB-V, UMUC-3, KU-7 and UMUC-13 were treated with gefitinib and vascular endothelial growth factor secretion was measured. The effects of gefitinib on vascular endothelial growth factor promoter, proliferation, cell cycle and downstream signals were evaluated. In vivo 253JB-V and UMUC-13 were injected into nude mice and tumors were treated with 2 mg gefitinib per day. Tumor kinetics were determined and the levels of phospho-epidermal growth factor receptor (Biosource), vascular endothelial growth factor, phospho-vascular endothelial growth factor (Cell Signaling Technology), angiogenesis and apoptosis were measured. RESULTS: Epidermal growth factor receptor (Neomarkers, Fremont, California) phosphorylation was blocked efficiently in all cell lines at concentrations of 0.5 microM or greater. Gefitinib (1 microM) induced an accumulation of cells in G0/G1 without apoptosis in 253J B-V cells, whereas it had no effect in other cell lines. Gefitinib inhibited vascular endothelial growth factor secretion in 253JB-V and UMUC-13 (concentration inhibiting a 50% response 0.5 and 0.1 microM, respectively) but not in UMUC-3 or KU-7. Gefitinib decreased vascular endothelial growth factor promoter activity in 253JB-V and UMUC-13 by 40% to 60%. In vivo the growth of 253JB-V tumors was significantly inhibited by gefitinib, whereas no effect was demonstrated in UMUC-13 tumors. Vascular endothelial growth factor expression and vascular endothelial growth factor receptor activation were significantly decreased in 253JB-V tumors and to a greater extent in resistant UMUC-13 tumors. Gefitinib inhibited angiogenesis and induced apoptosis in sensitive 253JB-V tumors only. CONCLUSIONS: Epidermal growth factor receptor blockade exerts an anti-angiogenic effect on bladder cancer cells, in part by modulating vascular endothelial growth factor expression. However, down-regulation of vascular endothelial growth factor expression is not sufficient to inhibit bladder cancer growth and it should not be used as a predictor of the therapeutic efficacy of gefitinib.

Efficacy of artificial urinary sphincter implantation after failed bone-anchored male sling for postprostatectomy incontinence.

OBJECTIVES: To evaluate the feasibility and efficacy of artificial urinary sphincter placement after failed bone-anchored male sling for postprostatectomy stress urinary incontinence. METHODS: Eleven patients with postprostatectomy stress urinary incontinence who failed bone-anchored male sling underwent artificial urinary sphincter placement. All patients were evaluated before and after artificial urinary sphincter placement with a history and physical examination, pad score, and the incontinence section of the University of California, Los Angeles (UCLA)/RAND prostate cancer index (total score possible = 26). Urodynamic evaluation was performed before sphincter placement. RESULTS: The average age in our study population was 70 years (range, 51 to 80 years). The mean follow-up after artificial urinary sphincter placement was 14.2 months (range, 3 to 20 months). Incontinence was defined as mild (1 to 2 pads), moderate (3 to 5 pads), or severe (more then 5 pads). After sling placement, cure was defined as no pad use, failure as same pad usage, and improvement as fewer pads used. The severity of incontinence before artificial urinary sphincter placement was mild, moderate, and severe in 3, 1, and 7 patients, respectively. After artificial urinary sphincter placement the severity of incontinence was cured, mild, and moderate in 8, 2, and 0, respectively. One patient required artificial urinary sphincter removal because of infection. Mean UCLA/RAND scores increased from 10.8 to 19.7. Patient satisfaction after artificial urinary sphincter placement was 74.5%. No intraoperative complications or urethral injuries occurred. CONCLUSIONS: Artificial urinary sphincter placement after failed bone-anchored male sling is technically feasible and does not affect the short-term efficacy of the artificial sphincter.

Lift-assisted offset lithotomy: positioning for transurethral operations in morbidly obese.

The incidence of morbid obesity is rapidly increasing in the United States. This presents a unique challenge in the diagnosis, management, and surgical treatment of urologic disease. The use of the lithotomy position for transurethral procedures is often not possible because of the body habitus and equipment-specific weight limitations. During positioning, it becomes imperative to maintain the safety of both the patient and the operating room personnel. We present a new, bariatric lift-assisted positioning technique used in the management of a 311-kg morbidly obese man with high-grade, superficial, papillary urothelial carcinoma.

Extraction of UroLume endoprosthesis with one-stage urethral reconstruction using buccal mucosa.

Long-term analyses of the UroLume Endoprosthesis have shown conflicting results with regard to efficacy and restricture rates. The best management of recurrent urethra stricture disease at the site of a previous UroLume stent is unknown. We describe a previously unreported technique for transperineal excision of the UroLume for recurrent bulbar urethral stricture disease with one-stage reconstruction using buccal mucosa. At 9 months of follow-up, the patient was voiding well with no evidence of stricture recurrence.

Patient opinion of urologists' reimbursement.

OBJECTIVES: To determine patient assumptions and opinions of the billing and reimbursement process in an urban urologic practice. Healthcare policy and physician reimbursement has been discussed in political and economic forums; however, few studies exist that reflect a patient's perspective of reimbursement issues. METHODS: An anonymous, voluntary 11-question survey was given to 825 patients during a 10-week interval. The instrument measured patient perceptions on the amounts (in percentages) that would, and should, be covered by insurance carriers and collected by their urologist. It also measured the time frames perceived for these events to occur. Our aim was to evaluate their knowledge of office urologic reimbursement. RESULTS: Overall, 532 patients (75%) surveyed believed their insurance would cover 80% to 100% of their bill. A total of 309 patients (49%) thought their urologist would receive 80% to 100% of the bill, and 383 (60%) thought they should receive that level of compensation (P < 0.0001). Respondents with prior surgical contact thought their urologist would (P = 0.004) and should (P = 0.01) be reimbursed at a greater level than those without prior surgical contact. When asked about the time to reimbursement, 340 (73%) thought their doctor would be paid within 6 weeks compared with 453 (95%) who thought their urologist should be paid within that time (P < 0.0001). CONCLUSIONS: The survey responses demonstrated patients' convictions that their urologists should be reimbursed in a timely manner. Additional studies examining both patient and healthcare provider perspectives are needed to better educate both of these groups on the medical billing and reimbursement process.

The literature increasingly supports expectant (conservative) management of renal trauma--a systematic review.

BACKGROUND: The perfect degree of operative intervention in renal trauma is unknown. However, expectant management for most blunt renal trauma is the standard of care, and nonoperative management is increasingly accepted for stab wounds. The best treatment of gunshot wounds and vascular injuries is still unclear; however, recent data indicates that a trial of nonoperative therapy may be warranted in those not exsanguinating from the kidney. Conservative management has many benefits, the greatest of which is decreasing the rate of iatrogenic nephrectomy. We have reviewed the world's literature to determine the level of support for expectant management of renal injury. METHODS: The English language literature concerning renal trauma was identified with the assistance of Medline, and additional cited works not picked up in the initial search were obtained. One hundred and ten citations were ultimately reviewed dating back to 1947. RESULTS: Most modern citations support at least a trial of expectant management for renal trauma patients not exsanguinating from the kidney, and without ureteral or renal pelvis injuries. The treatment of renovascular injuries has less consensus, but it appears that 'conservative' management by the application of nephrectomy is often the best approach, although renovascular repair may be attempted in rare cases. CONCLUSION: Dozens of papers going back as far as 50 years seem to support the wider use of nonoperative therapy of renal injuries, although for unclear reasons, this approach is not yet universally accepted.

Breast carcinoma metastatic to the bladder and renal pelvis requiring fulguration.

Breast cancer metastatic to the bladder has rarely been reported in the literature. A patient presented to our institution with pathologically confirmed breast cancer metastatic to the bladder with renal pelvis involvement as seen on retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be the treatment of choice for breast cancer that has metastasized to the bladder because of the low rate of survival in patients with hematuria related to metastatic breast cancer.

Continent urinary diversion with a urachal remnant.

The Mitrofanoff procedure, first described in 1980, has been widely adopted for pediatric continent urinary diversion to increase patient independence and continence, decrease morbidity and infections, and preserve renal function. Although this principle employs the appendix primarily, numerous other tissue conduits have been described. We report a unique use of a urachal remnant as a continent conduit resulting in less morbidity by maintaining the integrity of the native urinary bladder, while maintaining patient continence and allowing easy and successful catheterization.