Surgical outcomes and complications associated with presurgical tyrosine kinase inhibition for advanced renal cell carcinoma (RCC).

BACKGROUND: Tyrosine kinase inhibitors (TKI) have dramatically changed the management paradigm of advanced renal cell carcinoma (RCC) and are increasingly being used preoperatively to achieve cytoreduction. OBJECTIVE: To review our case series of post-TKI surgical procedures to add to the current perioperative efficacy and complication profile. MATERIALS AND METHODS: Between October 2006 and February 2010, 14 cytoreductive nephrectomies, radical nephrectomies, and metastectomies were performed after neoadjuvant sunitinib or sorafenib for advanced RCC. During the same time frame, a control group of 73 consecutive patients underwent radical nephrectomy, cytoreductive nephrectomy, or metastectomy in the absence of prior systemic therapy. We compared the incidence of perioperative complications and outcomes after surgical procedures between the two cohorts. RESULTS: Median preoperative renal mass size was 11 cm (6.7-24.2 cm). Primary tumor shrinkage was seen in 57%; median shrinkage was 18% (8%-25%). The median treatment period was 17 weeks, and the median time from TKI discontinuation was 2 weeks. Compared with a control group and after adjusting for confounding covariates, presurgical TKI use was not associated with a significant increase in perioperative complications (50% vs. 40%, P = 0.25) or perioperative bleeding (36% vs. 34%, P = 0.97) but was associated with increased incidence and grade of intraoperative adhesions (86% vs. 58%, P = 0.001; grade 3 vs. 1, P = 0.002). CONCLUSIONS: Compared with the published reports, we observed less hemorrhagic and wound healing issues but a significant increase in incidence and severity of intraoperative adhesions, which can present a formidable technical challenge. Potential reasons for our lower complication rate could be increased time from TKI discontinuation to surgery, longer time to postoperative TKI re-initiation, increased use of preoperative angioembolization, and the lack of preoperative bevacizumab administration. Presurgical TKI therapy can permit effective surgical cytoreduction with a safety and complication profile equivalent to that of non-TKI-nephrectomy; however safety data continue to evolve, and preoperative TKI use requires further prospective investigation.

Prostatic urethral lift: two-year results after treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

OBJECTIVE: To evaluate the effectiveness of the prostatic urethral lift in relieving lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. METHODS: A total of 64 men, aged≥55 years, with moderate to severe symptomatic benign prostatic hyperplasia were treated and followed up at 6 Australian institutions. The treatment consisted of transurethral delivery of small implants to secure the prostatic lobes in an open condition, thereby reducing obstruction of the urethral lumen. The effectiveness, including International Prostate Symptom Score, quality of life, benign prostatic hyperplasia Impact Index, and peak urethral flow rate were assessed at 2 weeks and 3, 6, 12, and 24 months. The effect of this treatment on erectile and ejaculatory function was assessed using the Sexual Health Inventory for Men and Male Sexual Health Questionnaire for Ejaculatory Dysfunction. RESULTS: The prostatic urethral lift improved LUTS symptoms rapidly and durably. The International Prostate Symptom Score was reduced 42% at 2 weeks, 49% at 6 months, and 42% at 2 years in evaluable patients. The peak flow rate improved by ≥30% (2.4 mL/s) at all intervals compared with baseline. No compromise in sexual function was observed after this treatment. CONCLUSION: The present study demonstrated that LUTS and flow improvements without compromising sexual function. Although this was an early study with a small cohort, this therapy shows promise as a new option for patients with LUTS.

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy.

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.

Obstruction in modified Blalock shunts: a quantitative analysis with clinical correlation.

BACKGROUND: Despite numerous reports describing the clinical course of patients undergoing a modified Blalock-Taussig shunt (MBTS), there is limited information on shunt obstruction. No studies have quantified MBTS stenosis histopathologically and correlated that with demographic and clinical risk factors. METHODS: From June 2001 to June 2003, 155 patients had MBTS takedown. The shunt operation (at median age 6 days; shunt size 3.5 mm in 56 [36%]; 4 mm in 84 [54%]; 5 mm in 15 [10%]) was performed on cardiopulmonary bypass (CPB) in 96 patients (62%). At elective takedown (at median 8.1 months), the shunt was excised and histopathologically analyzed for maximal narrowing. Demographics and clinical variables including age, weight, shunt size and duration, diagnosis, use of cardiopulmonary bypass, blood products, anastomosis sites, and concomitant antegrade flow were then tested for correlation with shunt stenosis. RESULTS: The mean value for maximal narrowing of the shunt lumen was 34% +/- 22%, and 32 patients (21%) had greater than 50% stenosis. Myofibroblastic proliferation, often associated with organized thrombus, caused the obstruction. Smaller shunt size (<4 mm) was a statistically significant risk factor for stenosis greater than 50% (odds ratio [OR] = 2.51; p = 0.028). Other variables that showed a clinically important association with obstruction but did not reach statistical significance included age less than 14 days at shunt (OR = 2.08, confidence interval [CI] 0.8 to 5.2), shunt on bypass (OR = 2.07, CI 0.9 to 4.8), and platelet use at shunt operation (OR = 1.96, CI 0.9 to 4.4). CONCLUSIONS: Most MBTS develop stenosis by the time of takedown, and 21% have greater than 50% obstruction. Shunt size less than 4 mm is a risk factor for high-grade stenosis. Younger age, CPB, and use of platelets are other clinically important factors. Better conduits and suppression of intimal proliferation could potentially improve outcomes.