Does previous transurethral prostate surgery affect oncologic and continence outcomes after RARP?

We examined the effect of previous transurethral resection of the prostate (TURP) on multiple oncologic and continence outcomes after robotic-assisted radical prostatectomy (RARP). We performed a retrospective cohort study of a total of 2693 patients from 2007 to 2014 who underwent RARP. Patients were stratified into 49 patients who had previous TURP prior to RARP (group 1) and 2644 patients who had no TURP prior to RARP (group 2). We collected operative variables including estimated blood loss, operative time, and positive surgical margin (PSM) rates. Urinary continence, defined as 0 pads per day (PPD), and social continence, defined as 1-PPD, were also assessed. American Urological Association Symptoms Score (AUASS), overall ability to function sexually, and Expanded Prostate Cancer Index Composite (EPIC) questionnaire were evaluated at 3 and 12 months after RARP. Weakness of urinary stream (EPIC #4d) at 12 months imposed a greater problem for group 1 patients with prior TURP compared to group 2 patients without prior TURP (p = 0.012). PSM was not statistically significant between the two groups (p = 0.110). Group 1 patients had a greater PSM rate (30.61 %) as compared to group 2 (20.95 %). PSM locations in group 1 patients showed the most common locations at the posterior and apex. The difference between the two groups for AUASS, overall sexual function, estimated blood loss, operative time, urinary continence, and social continence was not statistically significant. We examined the effect of previous TURP on postoperative RARP continence and oncologic outcomes. This data can be used to counsel those with prior TURP before RARP.

Positive Surgical Margin Trends in Patients with Pathologic T3 Prostate Cancer Treated with Robot-Assisted Radical Prostatectomy.

INTRODUCTION: We analyzed the trends of positive surgical margin (PSM) location in patients who had pT3 disease at robot-assisted radical prostatectomy (RARP). We aimed to describe our changing incidence of PSMs in the largest series to date of patients with pT3 disease who were treated by RARP. METHODS: A single-institution, single-surgeon review was performed of all patients who underwent RARP from 2005 to 2011. Perioperative data were collected for all patients with pT3 prostate cancer from a prospectively maintained RARP database. The PSM incidence and rates were stratified by location. The PSM rates per location were trended over time. RESULTS: In total, 2478 consecutive patients underwent RARP between July 2005 and December 2011. Of these patients, 555 were found to have pT3 disease. The PSM rate for patients with pT3 disease was 47%. The PSM rate for patients with pT3a and pT3B disease was 42.8% and 60.6%, respectively. Over the duration of this study, the PSM rate in patients with pT3 disease decreased significantly from 70.6% in 2005 to 32.3% in 2011 (p=0.002). The apical PSM rate showed the greatest decrease during this period going from 52.9% in 2005 to 5.2% in 2011 (p=0.018). CONCLUSION: We present the largest series to date involving the treatment of locally advanced prostate cancer initially managed with RARP. Our findings suggest that patients with locally advanced prostate cancer can be treated with RARP with acceptable positive margin rates. Overall PSM rates improved nearly 40% over the 6.5-year period of this study.

Functional and oncologic outcomes of graded bladder neck preservation during robot-assisted radical prostatectomy.

PURPOSE: To describe our bladder neck dissection during robot-assisted radical prostatectomy (RARP), to describe the degrees of robot-assisted bladder neck preservation (R-BNP) we have encountered, and to determine the effect of increasing R-BNP on postoperative continence and positive surgical margin (PSM) rates. PATIENTS AND METHODS: We performed a retrospective analysis of 599 patients who underwent robot-assisted radical prostatectomy (RARP) by a single surgeon (DIL). All bladder neck dissections were graded between 1 and 4; higher grades corresponded to an increasing degree of robot-assisted bladder neck preservation (R-BNP). After grouping patients by R-BNP grade, postoperative continence and positive surgical margin (PSM) rates were compared. The association between R-BNP and continence was also assessed using multivariate binary logistic regression models. RESULTS: Similar outcomes were seen for two definitions of continence (0 pads per day [ppd]; 0 ppd or security pad, respectively). A higher proportion of patients were continent at 3 months postoperatively who received grade 4 compared with grade 1 (P=0.043; P=0.001) and grade 2 (P=0.006; P=0.009); and grade 3 compared with grade 1 (P=0.048; P=0.002) and grade 2 (P=0.009; P=0.030) R-BNP. There was no difference between grade 1 and 2 (P=0.541; P=0.064), and grade 3 and 4 (P=0.898; P=0.584) R-BNP. At 1 year postoperatively, there was no difference among the four groups in continence rate (P=0.771; P=0.411). R-BNP was an independent predictor of continence at 3 months (odds ratio [OR] [95% confidence interval (CI)]=1.33 [1.06-1.67]; OR [95% CI]=1.45 [1.1-1.82]), but not at 1 year (OR [95% CI]=1.07 [0.82-1.39]; OR (95% CI)=1.30 [0.92-1.85]). There was no difference among the four groups in PSM rates (P=0.946). CONCLUSIONS: R-BNP is a graded, rather than all-or-none outcome. An increasing degree of R-BNP is associated with an earlier return to continence, without compromising oncologic outcomes.

Placenta Percreta With Invasion into the Urinary Bladder.

Placenta percreta is a rare condition, which can lead to significant morbidity and potentially mortality. We present a case of a 38-year-old woman who presented at 24 weeks gestation with vaginal bleeding and was found to have complete placenta previa with placenta percreta invading the urinary bladder. Her hospital course was complicated by bilateral pulmonary emboli. She underwent an exploratory laparotomy, repeat Caesarean section, and total abdominal hysterectomy. Because of placental invasion into the bladder, the procedure was complicated by bladder and ureteral injuries for which urology carried out repair. Postoperatively, the patient had a persistent bladder leak until postoperative day #39.

Prospective long-term analysis of nerve-sparing extravesical robotic-assisted laparoscopic ureteral reimplantation.

OBJECTIVE: To prospectively review our experience with extravesical robotic-assisted laparoscopic ureteral reimplantation to determine whether postoperative voiding dysfunction can be avoided with pelvic plexus visualization and to assess the efficacy of this approach for the treatment of vesicoureteral reflux (VUR). METHODS: We prospectively followed 150 patients who underwent bilateral extravesical robotic-assisted laparoscopic ureteral reimplantation by a single surgeon at an academic institution. Each patient was followed for a 2-year period. All 150 patients had primary VUR of grade 3 or greater bilaterally, with 127 having parenchymal defects found on renal scans. All patients were toilet trained before surgical intervention. The operation was performed with an extravesical transperitoneal approach with robotic assistance using the daVinci Surgical System. All patients underwent voiding cystourethrography at 3 months postoperatively to document the resolution of VUR. Voiding dysfunction was assessed in each patient by uroflow, postvoid residual urine volume, and a validated questionnaire. RESULTS: The operative success rate was 99.3% for VUR resolution on voiding cystourethrography. One patient with bilateral grade 5 VUR that was downgraded to unilateral grade 2 VUR was considered to have treatment failure. This patient ultimately underwent subsequent subureteral injection therapy after an episode of pyelonephritis. No patient experienced de novo voiding dysfunction. CONCLUSION: Bilateral nerve-sparing robotic-assisted extravesical reimplantation has the same success rate as the traditional open approaches, with minimal morbidity and no voiding complications in our series.

Neuroendocrine tumor of the bladder.

Small cell carcinoma (SCC) of the bladder is a rare and aggressive tumor associated with a poor prognosis. It often presents at a later stage than urothelial carcinoma of the bladder, and comprises less than 1% of bladder malignancies. A number of treatment algorithms have been used to treat bladder SCC, including cystectomy, partial cystectomy, radiotherapy, chemoradiotherapy, chemotherapy alone, and neoadjuvant/adjuvant chemotherapy. Presented is a case of SCC of the bladder, and the epidemiology, prognosis, and current treatment algorithms for patients with bladder SCC are reviewed.

Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand.

OBJECTIVES: Chemotherapeutic agents sensitize cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) via recruitment of the mitochondria-dependent activation of caspase and induction of apoptosis. This study was designed to evaluate whether gossypol, a phytochemical compound with BH3-mimetic property that functions as an inhibitor of Bcl2/BclXL, would sensitize cultured thoracic cancer cells to this death-inducing ligand. METHODS: Cancer cell lines from the lung (H460, H322), the esophagus (TE2, TE12), and the pleura (H290, H211) or primary normal cells were treated with gossypol+Apo2L/TRAIL combinations. Cell viability and apoptosis were evaluated by (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. Caspase 9 and 3 specific proteolytic activity in combination-treated cells was determined by fluorometric enzymatic assay. RESULTS: Gossypol, selectively cytotoxic to cancer cells and not primary normal cells, significantly sensitized thoracic cancer cells to Apo2L/TRAIL as indicated by 1.5- to more than 10-fold reduction of Apo2L/TRAIL 50% inhibitory concentration values in cells treated with gossypol+Apo2L/TRAIL combinations. Whereas less than 20% of cancer cells exposed to either gossypol (5 micromol/L) or Apo2L/TRAIL (20 ng/mL) were dead, more than 90% of cells treated with the drug combinations were apoptotic. Combination-induced cytotoxicity and apoptosis was completely abrogated either by overexpression of Bcl2 or by the selective caspase 9 inhibitor. This combination was not toxic to normal cells. CONCLUSION: Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway. This study provides evidence for the profound anticancer activity of this drug combination and should be further evaluated as a novel targeted molecular therapeutic for thoracic cancers.

Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126.

BACKGROUND: This study aimed to evaluate the impact of selective abrogation of either the MEK/ERK1/2 (UO126 or PD98059) or the PI3K/AKT (LY294002) signaling cascade on cell proliferation, motility and invasion and production of VEGF (collectively termed pro-metastasis phenotypes) in cultured malignant pleural mesothelioma (MPM) cells. MATERIALS AND METHODS: Treatment-induced cytotoxicity was evaluated by MTT or Annexin V assays. Cell motility was assessed by wound healing and Matrigel invasion assays. VEGF in conditioned media of cancer cells was measured by ELISA. RESULTS: LY294002 and UO126 significantly inhibited cell proliferation and clonogenicity of MPM cells in vitro. A substantial reduction of cell motility, Matrigel invasion as well as inhibition of basal or EGF-induced VEGF production were observed in drug-treated cells. CONCLUSION: The selective MEK or PI3K kinase inhibitors are equally effective in down-regulating the expression of pro-metastasis phenotypes, suggesting that MEK or PI3K are appropriate targets for the development of molecular therapeutics for malignant pleural mesothelioma.