Long-term Renal Preservation and Complication Profile With Ileal Ureter Creation.

OBJECTIVE: To examine long-term ileal ureter replacement results at over 32 years at our institution. Long segment or proximal ureteral strictures pose a challenging reconstructive problem. Ureteroureterostomy, psoas hitch, Boari flap, buccal ureteroplasty, and autotransplantation are common reconstructive techniques. We show that ileal ureter remains a lasting option. METHODS: We performed a retrospective review of patients undergoing open ileal ureter creation from 1989-2021. Patient demographics, operative history, and complications were examined. All patients were followed for changes in renal function. Demographic data were analyzed and Cox proportional hazard models were performed. RESULTS: One hundred and fifty-eight patients were identified with median follow-up time of 40 months. Eighty-one percent had a unilateral ileal ureter creation. Fifty percent were female, median age was 53.3. Twenty-seven percent of patients had radiation-induced strictures. Preoperatively, 56.3% of patients were chronic kidney disease stage 1-2 and 43.7% were stage 3-5. Post-operatively, 54% were stage 1-2 and 46% were stage 3-5. Cox proportional hazard models demonstrated no significant correlation between worsening renal function and stricture cause, bilateral repair, complications, or sex (biologically male or female). Seventy-seven percent had no 30-day complications. Clavien complications included grade 1 (18), grade 2 (4), grade 3 (9), and grade 4 (5). Long-term complications included worsening renal function (3%), incisional hernia (8.2%), and small bowel obstruction (6.9%). Five (3.1%) patients ultimately required dialysis and 5 (3.1%) patients developed metabolic acidosis. CONCLUSION: Ileal ureteral reconstruction is often a last resort for patients with complex ureteral injuries. Clinicians can be reassured by our long-term data that ileal ureteral creation is a safe treatment with good preservation of renal function and low risk of hemodialysis and metabolic acidosis.

Ileal Ureter Utilization in Patients With Previous Urinary Diversions.

OBJECTIVE: To evaluate a subset of patients who develop strictures requiring Ileal Ureter (IU) in the setting of prior urinary diversion or augmentation (ileal conduits, neobladders, continent urinary diversions). To our knowledge, there are no prior studies on patients with IU substitution into established lower urinary tract reconstructions. METHODS: A retrospective review of patients (18 years) undergoing IU creation from 1989 to 2021 was performed. A total of 160 patients were identified. In total, 19 (12%) patients had IUs into diversions. We examined demographics, stricture cause, diversion type, renal function, and postoperative complications. RESULTS: Nineteen patients were identified. Sixteen were male. Mean age was 57.7(SD 17.0) years. Diversions included continent urinary reservoirs (4), neobladders (5), ileal conduits (7), and bladder augmentations with Monti channels (3). Fifteen had unilateral surgery, and 4 had bilateral "reverse 7" IU creation. Average length of stay was 7.6 days (SD 2.9). Average follow-up was 32.9 months (SD 27). Mean preoperative creatinine was 1.5 (SD 0.4); mean postoperative creatinine at most recent follow-up was 1.6 (SD 0.7). There was no significant difference between pre- and postoperative creatinine (P = .18). One patient had a ventriculoperitoneal Shunt infection resulting ventriculoperitoneal shunt externalization, 1 had Clostridium difficile infection potentially causing an entero-neobladder fistula, 2 with ileus, 1 urine leak, and 1 wound infection. None required renal replacement therapy. CONCLUSION: Patients with urinary diversions and prior bowel reconstructive surgeries with subsequent ureteral strictures are a challenging cohort of patients. In properly selected patients, ureteral reconstruction with ileum is feasible and preserves renal function with minimal long-term complications.

Early and Midterm Complications of the Continent Catheterizable Indiana Pouch Urinary Diversion: A 7-year Experience.

OBJECTIVES: To describe the most recent 7 year experience with 137 Indiana pouch patients at a single institution and provide data on complications with this type of urinary diversion during the first postoperative year. METHODS: We queried our bladder cancer database to identify all patients who underwent cystectomy with continent catheterizable urinary reservoir between 2012 and 2018. Pre-, intra-, and postoperative data were collected. Complications were stratified into early (within 90 days) and midterm (90-365 days). The primary outcomes were postoperative complications, and overall and cancer-specific mortality. RESULTS: A total of 137 patients underwent open cystectomy with Indiana pouch creation. Of these, 93% were radical cystectomies. On average, the operation took 422 minutes. There were 53 (39%) patients who experienced any type of complication during the first postoperative year (Clavien II-V). Twenty-five patients (18.2%) readmitted in the early postoperative period vs 18 (13.1%) patients midterm. There were 10 (7.3%) patients that required early reoperation and 11 (8%) in the midterm period. The overall mortality rate was 1.5% early and 3.7% midterm, with the majority of the mortality rate attributed to cancer progression (85.7%). CONCLUSION: Patients undergoing continent catheterizable reservoir urinary diversion appear to have comparable complication rates to other urinary diversions published in the literature. At high-volume urologic institutions, Indiana Pouch creation is a suitable option for select patients desiring a continent diversion.

Longitudinal Health Related Quality of Life After Open Radical Cystectomy: Comparison of Ileal Conduit, Indiana Pouch, and Orthotopic Neobladder.

OBJECTIVE: To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. MATERIALS AND METHODS: The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. RESULTS: A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p <.005) yet still experienced similar improvements in health related quality of life commensurate with the other diversion cohorts. There was a significant difference in physical well-being favoring neobladder over IC or Indiana Pouch urinary diversions (p <.05). CONCLUSIONS: To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

Surgical Management of Retrocrural Disease in Germ Cell Tumors: Outcomes and Evolution of Practice.

INTRODUCTION: Residual retrocrural disease in testis cancer following chemotherapy is a surgical challenge. We sought to assess the outcomes and evolution with surgical management of residual retrocrural disease. MATERIALS AND METHODS: We identified 2,788 testicular cancer patients from 1990 to 2010 who underwent retroperitoneal surgery for metastatic testicular cancer at our institution. Patients who also underwent postchemotherapy staged or concurrent retrocrural dissections were stratified for analysis. Surgical approach, clinical characteristics, additional procedures, complications and outcomes were evaluated. RESULTS: Retrocrural dissection was performed in 211 patients. Histology of retrocrural disease demonstrated teratoma in 72%, necrosis in 15.2%, active germ cell cancer in 8.1% and malignant transformation in 2.4%. Our preferred surgical approach to the retrocrural space has evolved over time. Earlier approaches from 1990 to 1995 favored a single thoracoabdominal incision (17, 25%), midline transabdominal incision (22, 32.4%), or with a concurrent or staged thoracotomy (29, 42.6%). A transabdominal/transdiaphragmatic approach at the time of midline retroperitoneal lymph node dissection has been used more frequently in 55% of contemporary cases, decreasing the need for thoracotomies. Patients undergoing a transabdominal/transdiaphragmatic approach had fewer complications (p=0.006) and required fewer associated procedures (p=0.001) and a shorter length of stay (5 vs 6 days, p=0.184). CONCLUSIONS: Metastatic testis cancer to the retrocrural space is surgically challenging however complete resection is needed to maintain an expected excellent oncologic outcome. Coordination between urological and thoracic surgeons for an individualized approach is important. We have found that a transabdominal/transdiaphragmatic approach where appropriate has resulted in fewer complications.

Robotic and open partial nephrectomy for intermediate and high complexity tumors: a matched-pairs comparison of surgical outcomes at a single institution.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when controlling for tumor and patient complexity.Methods: A retrospective review of 222 patients undergoing partial nephrectomy was performed. Patients with intermediate (nephrometry score NS 7-9) or high (NS 10-12) complexity tumors were matched 2:1 for RPN:OPN using NS, Charlson Comorbidity Index (CCI), and BMI. Patient demographics, peri-operative values, renal function, and complication rates were analyzed and compared.Results: Seventy-four OPN patients were matched to 148 RPN patients with no difference in patient demographics. Estimated blood loss in OPN patients was significantly higher (368.5 vs 210.5 mL, p < 0.001) as was transfusion rate (17% vs 1.6%, p < 0.001). Warm ischemia time was longer in OPN (25.5 vs 19.7 min, p = 0.001) while operative time was reduced (200.5 vs 226.5 min, p = 0.010). RPN patients had significantly shorter hospitalizations (5.3 vs 3.0 days, p < 0.001). GFR decrease after one month was not statistically significant (12.9 vs 6.6 ml/min, p = 0.130). Clavien III-V complications incidence was higher for OPN compared to RPN although not significantly (20.3% vs 10.8%, p = 0.055).Conclusion: When matching for tumor and patient complexity, RPN patients had fewer high grade post-operative complications, decreased blood loss, and shorter hospitalizations. RPN is a safe option for patients with intermediate and high complexity tumors.

Improving postoperative quality of care in germ cell tumor patients: Does scheduled alvimopan, acetaminophen, and gabapentin improve short-term clinical outcomes after retroperitoneal lymph node dissection?

INTRODUCTION: To determine the benefits of alvimopan and multimodal pain management strategies in men undergoing retroperitoneal lymph node dissection for testicular cancer. METHODS: A retrospective cohort study was completed in men undergoing retroperitoneal lymph node dissection from January 2017 to May 2018. Patients were placed into the 3-drug, 2-drug, and control cohorts as a result of a prospectively determined protocol during the study period. Men in the 3-drug group were managed using alvimopan 12 mg PO the morning of surgery then BID until bowel movement, gabapentin 300 mg daily, and acetaminophen 1,000 mg q6H. The 2-drug group was managed with the above regimen excluding alvimopan. Controls were treated per our standard perioperative pathway. Primary outcomes were length of stay, IV narcotic consumption, bowel movement during hospitalization, and time to bowel movement and assessed in multivariate models controlling for operative time, concomitant surgery, chemotherapy receipt, and residual mass size. RESULTS: One-hundred and fifty-two consecutive patients underwent RPLND (42 3-drug, 38 2-drug, and 72 controls). Multivariable models indicated that the 3-drug (IRR 0.89, P < 0.0001) and 2-drug group (IRR 0.87, P = 0.0209) had shorter hospital stays than controls. Men in the 3-drug group required less narcotic pain medication than the 2-drug (ß -8.16, P = 0.0405) and the control (ß -8.16, P = 0.0302) group. Men receiving alvimopan (3-drug) were almost 6 times more likely than the 2-drug group (odds ratio 5.94, P < 0.0001) and 4 times more likely than the control group (odds ratio 3.86, P = 0.0017) to have a bowel movement during hospitalization. Men in the 3-drug group had the quickest return of bowel movements. CONCLUSIONS: Multimodal pain management improves length of stay in men undergoing retroperitoneal lymph node dissection for testis cancer. The addition of alvimopan allows for quicker return of bowel movements and reduces overall narcotic requirements.

A Prospective Program to Reduce the Clinical Incidence of Clostridium difficile Colitis Infection after Cystectomy.

PURPOSE: The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of C. difficile and assessed its impact on clinical C. difficile infection rates compared to historical matched controls. MATERIALS AND METHODS: Prospective C. difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients who underwent cystectomy before the initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Patients who screened positive were placed in contact isolation and treated prophylactically with metronidazole. Multivariable models were built on an intent to screen basis and an effectiveness of screening basis to determine whether screening reduced the rate of symptomatic C. difficile infection postoperatively. RESULTS: With the implementation of the screening protocol the C. difficile infection rate declined from 9.4% to 5.5% (OR 0.52, p = 0.0268) in patients on the intent to screen protocol and from 9.2% to 4.9% in those on the effectiveness of screening protocol (OR 0.46, p = 0.0174). CONCLUSIONS: C. difficile screening prior to cystectomy is associated with a significant decrease in the rate of clinically symptomatic infection postoperatively. These results should be confirmed in a randomized controlled trial.

Long term outcomes in the use of ileal ureter for radiation-induced ureteral strictures.

PURPOSE: Radiation-induced ureteral stricture disease poses significant surgical challenges. Ureteral substitution with ileum has long been a versatile option for reconstruction. We evaluated outcomes in patients undergoing ileal ureter replacement for ureteral reconstruction due to radiation-induced ureteral stricture versus other causes. METHODS: Between July 1989 and June 2013, 155 patients underwent consecutive ileal ureter creation. The study cohort included 104 patients with complete data sets and at least 7 months of follow up. Records were retrospectively reviewed with regard to demographics, indications, complications, and renal deterioration. RESULTS: Surgical indications included radiation-induced stricture in 23 (22%) and non-radiation-induced stricture in 81 (78%). Comparing ileal ureter substitution due to radiation versus other stricture etiologies, no statistical significance was observed in regard to age (45.6 vs. 51.2, p = 0.141), hospital length of stay in days (8.8 vs. 7.7, p = 0.216), percent GFR loss (MDRD-4 vs. -5%, p = 0.670 and CKD-EPI-7 vs. -6%, p = 0.914), 30-day surgical complications (26.1 vs. 30.1%, p = 0.658), metabolic acidosis (8.7 vs. 1.2%, p = 0.059), and renal failure requiring dialysis (4.3 vs. 1.2%, p = 0.337). Fistula formation (13.0 vs. 3.7%, p = 0.095), partial small bowel obstructions (21.7 vs. 7.4%, p = 0.063), and small bowel obstructions requiring reoperation (13.0 vs. 1.2%, p = 0.033) approached or reached statistical significance. Using Kaplan-Meier methodology, there was no difference in time to worsening renal outcome between the radiation and non-radiation groups (p > 0.05). CONCLUSION: Ureteral substitution with ileum is an effective reconstructive option for radiation-induced ureteral strictures in carefully selected patients.

Long-term Health-related Quality of Life Outcomes Following Radical Cystectomy.

OBJECTIVE: To evaluate the long-term (>5 years) health-related quality of life (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP), neobladder (NB), and ileal conduit (IC). MATERIALS AND METHODS: The departmental radical cystectomy database was queried to identify patients who underwent radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009 and had not died. Three hundred patients were identified and sent the validated Bladder Cancer Index instrument. RESULTS: A total of 128 (43%) patients completed the survey. When adjusted for gender, age at surgery, surgeon, and time since surgery, IC and IP patients had significantly better urinary function than NB patients (P = .0013). Sexual bother was less in NB than IP (P = .0387). Among men ≥65 years of age, IC patients had significantly better urinary function (P = .0376) than NB patients (91.6 vs 49.4, respectively). Among men <65 years of age, IC and IP patients (76.0 and 82.8, respectively) had significantly better urinary function than NB patients (50.7) (P = .0199). Among women greater than 65 years, bowel bother was significantly better (P = .0095) for IC patients than IP patients (44.8 vs 69.5, respectively). CONCLUSION: Urinary diversion type after radical cystectomy affects HRQOL differently in long-term survivors. Age and gender at surgery influenced HRQOL based on diversion procedure. Urinary function but not urinary bother was significantly better in IC and IP compared to NB diversions. Prospective longitudinal studies using validated HRQOL tools will further help guide preoperative diversion choice decisions between patient and surgeon.

Preoperative Nomograms for Predicting Renal Function at 1 Year After Partial Nephrectomy.

INTRODUCTION: Partial nephrectomy (PN) reduces the risk of postoperative chronic renal insufficiency (CRI). However, some patients still develop CRI after PN, and may eventually require dialysis. Being able to predict renal function before PN helps in counseling patients and managing expectations. We aimed to construct nomograms that predict estimated glomerular filtration rates (eGFRs), defined by the modification of diet in renal disease (MDRD) and the chronic kidney disease epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only preoperative covariates as predictors. PATIENTS AND METHODS: We identified patients who underwent PN in our institution between 2004 and 2016, with known postoperative serum creatinine levels at 1 year. The preoperative covariates included patients' demographics, chronic comorbid conditions, tumor characteristics, and preoperative renal status. The endpoints were eGFRs at 1 year after PN, calculated using the MDRD and the CKD-EPI formulae. We first identified preoperative covariates with significant associations with the endpoints by Pearson correlation and independent samples t-test. Suitable covariates were then included in two multivariate linear regression models, for constructing and internally validating two nomograms. RESULTS: 461 patients were eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73 m2 increased from 25% before PN to 35% at 1 year after PN. We included age, gender, African American race, body mass index, preoperative creatinine level, ipsilateral renal volume, solitary kidney status, tumor diameter, hypertension, diabetes, ischemic heart disease, and previous stroke in the multivariate linear regression models for nomogram construction. Internal validation showed bootstrap-corrected coefficients of determination of 0.61 and 0.70, for predicting eGFRs defined by the MDRD and CKD-EPI formulae, respectively. CONCLUSIONS: We constructed and internally validated two nomograms to predict eGFRs at 1 year after PN, using only preoperative covariates as predictors.

Ureteral Reconstruction With Ileum: Long-term Follow-up of Renal Function.

OBJECTIVE: To assess long-term renal preservation and surgical outcomes in patients undergoing ureteric substitution with ileum. This has been a mainstay of reconstruction options for lengthy ureteral defects. METHODS: Consecutive patients aged 18 or older undergoing ileal ureters at our institution were retrospectively reviewed (from 1989 to June 2013). Patients with <6 months of follow-up were excluded. Demographic, surgical, and renal functional outcomes were reviewed. Renal function was assessed by the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease Study equations. RESULTS: Of the 108 patients meeting the inclusion criteria, 86 (79.6%) had single-renal unit reconstruction and 22 had bilateral reconstruction. Eighty-four (77.8%) had radiation-induced stricture and 24 had iatrogenic or trauma-induced strictures. The median follow-up was 51 months (interquartile range: 22-112). Short-term complications included Clavien grade I (16 [14.8%]), Clavien grade II (3 [2.8%]), Clavien grade III (9 [8.3%]), and Clavien grade IV (3 [2.8%]). Long-term complications included fistula in 6 patients (5.6%), renal failure requiring dialysis in 2 patients (1.9%), hyperchloremic metabolic acidosis in 4 patients (3.7%), and incisional hernia in 11 patients (10.2%). Nine patients (8.3%) had small-bowel obstructions; 3 (2.8%) required adhesiolysis. Four patients (3.7%) had an anastamotic stricture. Nineteen patients (17.6%) had worsening renal function. Cox proportional hazards regression found that those with bilateral repair were at 3.7 times increased risk of worsening renal function (P = .02). CONCLUSION: Ureteral substitution with ileum provides an effective and versatile long-term reconstructive option with minimal renal function compromise in properly selected patients. Bilateral reconstruction may contribute to worse long-term renal function.

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

A Phase II Trial of Dovitinib in BCG-Unresponsive Urothelial Carcinoma with FGFR3 Mutations or Overexpression: Hoosier Cancer Research Network Trial HCRN 12-157.

Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non-muscle-invasive urothelial carcinoma of the bladder (NMIUC) population.Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC (>2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate.Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut-, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3-4 event. Six-month CR rate was 8% (0% in IHC+ Mut-; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94-5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment.Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003-11. ©2016 AACR.

Primary Choriocarcinoma of the Bladder: A Case Report and Review of Literature.

Primary choriocarcinoma of the urinary bladder is a rare entity, and should be distinguished from urothelial carcinoma with trophoblastic differentiation. The leading treatment modalities include surgical extirpation, chemotherapy, and radiation; however, survival remains poor. Herein we describe a rare case of choriocarcinoma of the bladder in a man who presented for evaluation with hematuria and subsequently underwent radical cystectomy with urinary diversion. Diagnosis of extragonadal germ cell tumor was confirmed using fluorescence in situ hybridization identification of isochromosome 12p.

Management of Pelvic Metastases in Patients With Testicular Cancer.

OBJECTIVE: To evaluate the clinicopathologic features and predictors of pelvic metastasis in patients with germ cell tumors. METHODS: Between 1990 and 2009, 2722 patients undergoing retroperitoneal lymph node dissection (RPLND) were prospectively included in our institution's testis cancer database. Patients with pelvic disease were identified and clinicopathologic features were analyzed. RESULTS: Of the 134 patients, 14.5% had a history of prior groin surgery. At the time of referral, 98% had received prior chemotherapy, 19.4% had undergone prior RPLND, and 24% presented as late relapse. Surgery consisted of pelvic excision alone in 37 (27.6%) and pelvic excision with primary RPLND in 2 (1.5%) or with postchemotherapy RPLND in 95 (70.9%). Median pelvic mass size was 6.5 cm. Pathology of pelvic disease revealed teratoma in 74 (55%), nonseminomatous germ cell tumor in 28 (21%), sarcoma in 8 (6%), and necrosis in 22 (16.5%). Patients with pelvic metastases had a statistically higher initial stage of presentation (P <.001) and had a higher incidence of prior groin surgeries (P <.001). CONCLUSION: Pelvic metastasis in testicular cancer is uncommon and can be a site of late relapse. These patients tend to present with high-volume retroperitoneal disease or a history of prior groin surgeries. Surgery is curative in most patients, and pelvic pathology was teratoma in more than half.

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology.

AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity.

OBJECTIVES: Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC). MATERIALS AND METHODS: A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100mg once daily for 28±7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as≥60% of patients with miUCB completing therapy without treatment-related dose-limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test. RESULTS: The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) had

Risk of Recurrence for Clinical Stage I and II Patients With Teratoma Only at Primary Retroperitoneal Lymph Node Dissection.

OBJECTIVE: To evaluate the oncologic outcomes of patients with retroperitoneal teratoma only at primary retroperitoneal lymph node dissection (RPLND) who did not receive adjuvant chemotherapy. MATERIALS AND METHODS: Between 1979 and 2010, 23 patients with clinical stage (CS) I and II disease underwent primary RPLND at our institution with teratoma only in the retroperitoneum. No patient received adjuvant chemotherapy and the minimum follow-up was 2 years. RESULTS: At the initial diagnosis, 13 patients (56.5%) had CS I disease and 10 patients (43.5%) had CS II disease. Pathologic staging demonstrated IIA in 13 patients (56.5%), IIB in 8 patients (34.8%), and IIC in 2 patients (8.7%). The 5-year disease-free survival (DFS) was 100% with a median follow-up of 5.8 years (range, 2.1-25.4). DFS was not significantly different comparing pathologic stage IIA vs IIB/IIC disease (P = .73). Two patients (14%) developed late relapses. One patient had a pelvic recurrence 11 years after primary RPLND. Final pathology from the pelvic resection demonstrated embryonal carcinoma. He remains disease free after his second surgery. The second patient had a contralateral retroperitoneal recurrence with yolk-sac tumor and teratoma 11 years after primary RPLND. He was treated with chemotherapy followed by postchemotherapy RPLND. CONCLUSION: The relapse rate for patients with teratoma only at primary RPLND is low irrespective of PS. Adjuvant chemotherapy is therefore not recommended in the management of these patients.