Evaluating the safety of intraoperative instillation of intravesical chemotherapy at the time of nephroureterectomy.

BACKGROUND: Urothelial carcinoma (UC) is a common cancer affecting many patients in the United States. Nephroureterectomy remains the gold standard for the treatment of high grade upper tract disease or low grade tumors that are not amenable to endoscopic management. Recent reports have shown a decrease in UC recurrence in patients who underwent nephroureterectomy and who had Mitomycin C (MMC) instilled into the bladder at the time of catheter removal. At our institution instillation of intravesical MMC at the time of nephroureterectomy has been common for more than 10 years. Given the recent data, we sought to formally describe our experience with and evaluate the safety of intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy. METHODS: We retrospectively reviewed 51 patients who underwent intraoperative intravesical instillation of cytotoxic chemotherapy (MMC (n = 48) or adriamycin (n = 3)) at the time of nephroureterectomy (2000-2012). The procedure was performed in a similar fashion by 8 different surgeons from the same institution, with drainage of the bladder prior to management of the bladder cuff. Patient characteristics and perioperative data including complications out to 90 days after surgery were collected. Perioperative complications for all patients were graded using the modified Clavien-Dindo classification. RESULTS: Twenty-four men and 27 women underwent intraoperative intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy. Median age at the time of operation was 74 years (range 48-88). Median dwell time was 60 min. Twenty three patients had a total of 45 perioperative complications. The majority (36/45) were Clavien grades I and II. No patients experienced any intraoperative or postoperative complications attributable to MMC or Adriamycin instillation. CONCLUSION: Intraoperative intravesical instillation of cytotoxic chemotherapy at the time of nephroureterectomy is safe and feasible. Multicenter trials to study the efficacy of early cytotoxic chemotherapy administration to prevent recurrence of bladder urothelial carcinoma following nephroureterectomy are warranted.

Do ureteric stent extraction strings affect stent-related quality of life or complications after ureteroscopy for urolithiasis: a prospective randomised control trial.

OBJECTIVE: To determine whether ureteric stent extraction strings affect stent-related quality of life (QoL) or increase complications after ureteroscopy (URS) for stone disease. PATIENTS AND METHODS: In all, 68 patients undergoing URS (October 2011 to May 2013) for stone disease were randomised to receive a ureteric stent with or without an extraction string. Patients completed the Ureteric Stent Symptom Questionnaire (USSQ) on postoperative days 1 and 6, and 6 weeks after stent removal. Pain was assessed at stent removal. Adverse events, including early stent removal, stent migration, retained stent, urinary tract infection (UTI), emergency room (ER) visits and postoperative phone calls were monitored. RESULTS: There was no difference in stent-related QoL as measured by the USSQ between those with and without a stent extraction string, pain at stent removal between those who pulled their stent independently vs those who underwent cystoscopy for stent removal, or in the rate of UTIs, ER visits or phone calls between groups. Five patients (four female, one male) removed their stent early by inadvertently pulling the string; none required replacement. Patients without a string had a significantly longer period with the postoperative ureteric stent (10.6 vs 6.3 days, P < 0.001). One patient without a stent string retained her ureteric stent for 6 months, which was removed by cystoscopy without incident. CONCLUSION: Ureteric stent extraction strings may offer several advantages without increasing stent-related urinary symptoms, complications, or postoperative morbidity.

An update in the treatment of male urinary incontinence.

PURPOSE OF REVIEW: Male urinary incontinence affects a significant number of elderly men and the successful treatment has the potential to significantly improve their quality of life. RECENT FINDINGS: Stress urinary incontinence, overflow incontinence and detrusor overactivity are the major categories of urinary incontinence affecting men. Although the surgical standards of care have not changed significantly for urinary incontinence, there have been recent advances with minimally invasive techniques, which show promise. SUMMARY: The treatment of male urinary incontinence is constantly evolving, with recent advances in minimally invasive procedures.

Prognostic Model for Predicting Survival in Patients with Disease Recurrence Following Radical Cystectomy.

BACKGROUND: Although the natural history of urothelial carcinoma of the bladder (UCB) from radical cystectomy (RC) to disease recurrence (DR) has been investigated intensively, the course of patients who have experienced DR after RC for UCB remains poorly understood. OBJECTIVE: To evaluate the prognostic value of the Bajorin criteria that consists of two risk factors: Karnofsky performance status (KPS) and the presence of visceral metastases (VMs) in patients with DR after RC for UCB. Furthermore, to identify additional factors associated with cancer-specific mortality (CSM) and thus build a multivariable model to predict survival after DR. DESIGN, SETTING, AND PARTICIPANTS: We identified 967 patients with UCB who underwent RC at 17 centers between 1979 and 2012 and experienced DR. Of these, 372 patients had complete data we used for analysis. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable Cox regressions analysis was performed. We used a forward stepwise selection process for our final multivariable model. RESULTS AND LIMITATIONS: Within a median follow-up of 18 mo, 266 patients died of disease. Cancer-specific survival at 1 yr was 79%, 76%, and 47% for patients with no (n=105), one (n=180), and two (n=87) risk factors (p<0.001; c-index: 0.604). On multivariable analyses, we found that KPS <80%, higher American Society of Anesthesiologists score, anemia, leukocytosis, and shorter time to DR (all p values <0.034) were independently associated with increased CSM. The combination of time to DR and KPS resulted in improved discrimination (c-index: 0.694). CONCLUSIONS: We confirmed the prognostic value of KPS and VMs in patients with DR following RC for UCB. We also found several other clinical variables to be associated with worse CSM. We developed a model for predicting survival after DR inclusive of time to DR and KPS assessed at DR. If validated, this model could help clinical trial design. PATIENT SUMMARY: We developed a model to predict survival following disease recurrence after radical cystectomy for urothelial carcinoma of the bladder, based on time to disease recurrence and Karnofsky performance status.

Prostate cancer vaccines in combination with additional treatment modalities.

Immunotherapy has been investigated in both preclinical studies and clinical trials as a new therapy for prostate cancer. Vaccines, including those that utilize dendritic cells, viruses, or DNA, immunize against prostate-specific antigen and prostatic acid phosphatase. The vaccines have long been studied as monotherapy for the cancer, but increasingly more trials have been initiated in combination with other modalities. These include radiation, chemotherapy, and androgen deprivation therapy. This review describes and discusses the various combinations of vaccine immunotherapies.

Minimal changes in the systemic immune response after nephrectomy of localized renal masses.

OBJECTIVES: Renal cell carcinoma (RCC) is an immunogenic tumor, and multiple immunostimulatory therapies are in use or under development for patients with inoperable tumors. However, a major drawback to the use of immunotherapy for RCC is that renal tumors are also immunosuppressive. As a result, current immunotherapies are curative in<10% of patients with RCC. To better understand the systemic immune response to RCC, we performed a comprehensive examination of the leukocyte and cytokine/chemokine composition in the peripheral blood of patients with localized clear cell renal tumors pre- and post-nephrectomy. METHODS AND MATERIALS: Peripheral blood samples were taken from 53 consented subjects with renal masses before cytoreductive nephrectomy and again at clinic visits approximately 30 days after nephrectomy. Samples were also obtained from 10 healthy age- and gender-matched controls. Blood samples from clear cell RCC subjects were analyzed by multi-parameter flow cytometry to determine leukocyte subset composition and multiplex array to evaluate plasma proteins. RESULTS: Pre-nephrectomy, clear cell tumors were associated with systemic accumulations of both "exhausted" CD8+ T cells, as indicated by surface BTLA expression, and monocytic CD14(+)HLA-DR(neg)CD33(+) myeloid-derived suppressor cells (MDSC). Subjects with T3 clear cell RCC also had a unique pro-tumorigenic and inflammatory cytokine/chemokine profile characterized by high serum concentrations of IL-1ß, IL-2, IL-5, IL-7, IL-8, IL-17, TNF-α, MCP-1 and MIP-1ß. At an early post-nephrectomy time point (~30 d), we found the systemic immune response to be largely unaltered. The only significant change was a decrease in the mean percentage of circulating BTLA(+)CD8(+) T cells. All other cellular and soluble immune parameters we examined were unaltered by the removal of the primary tumor. CONCLUSIONS: In the first month following surgery, nephrectomy may relieve systemic CD8 T cell exhaustion marked by BTLA expression, but continuing inflammation and MDSC presence likely counteract this positive effect. Future determination of how this systemic immune signature becomes altered during metastatic progression could provide novel targets for neoadjuvant immunotherapy in RCC.

Improving access to urologic care for rural populations through outreach clinics.

OBJECTIVE: To determine the effect of outreach clinics on access to urologic care in a state with a large rural population. This is especially pertinent given the predicted shortage of urologists over the next decade and the trend toward practice in urban area. METHODS: We analyzed provider level data from urologic practices within the state of Iowa using information from 2 publicly available sources: (1) the Office of Statewide (Iowa) Clinical Education Programs, which collects detailed information on visiting consultant urologists (VCU), and (2) the Iowa Physician Information System, which tracks demographic and professional data on all active physicians in Iowa. Factors analyzed included percent of counties and Iowans served by urologists and travel distances/times for patients and physicians. RESULTS: Currently, 57% of Iowans are within 30 minutes of a urologist's primary office, increasing to 84% with VCU outreach clinics. Fifty-five urologists, including 40 of 69 (58%) of Iowa-based urologists, perform outreach within Iowa, accounting for 198 clinic days and 20,400 miles of travel per month. CONCLUSION: Within Iowa, the lack of rural urologists has been mitigated, in part, by an extensive VCU network. However, improved access has required significant effort from urologists in both time and miles traveled. This study is the first to show how a rural state can effectively use physician outreach clinics to provide specialized urologic care to underserved, rural communities.