Shandra Wilson

Alvimopan Accelerates Gastrointestinal Recovery After Radical Cystectomy: A Multicenter Randomized Placebo-Controlled Trial

BACKGROUND Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS). OBJECTIVE To assess the efficacy of alvimopan to accelerate GI recovery after RC. DESIGN, SETTING, AND PARTICIPANTS We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics. INTERVENTION Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed. RESULTS AND LIMITATIONS Patients were randomized to alvimopan (n=143) or placebo (n=137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p<0.0001), shorter mean LOS (7.4 vs 10.1 d; p=0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p<0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p=0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy. CONCLUSIONS Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo. PATIENT SUMMARY This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00708201.

A study of high‐dose oral silybin‐phytosome followed by prostatectomy in patients with localized prostate cancer

Silibinin is a polyphenolic flavonolignan derived from milk thistle (Silybum marianium) with anti‐oxidant properties. The purpose of the current trial was to determine the tissue and blood effects of high‐dose silybin‐phytosome in prostate cancer patients.

SWOG S0353: Phase II Trial of Intravesical Gemcitabine in Patients with Nonmuscle Invasive Bladder Cancer and Recurrence after 2 Prior Courses of Intravesical Bacillus Calmette-Guérin

PURPOSE Prior phase II studies of intravesical gemcitabine have shown it to be active and well tolerated, but durable responses in patients with nonmuscle invasive bladder cancer who have experienced recurrence after bacillus Calmette-Guérin treatment are uncommon. We performed a multi-institutional phase II study within the SWOG (Southwest Oncology Group) cooperative group to evaluate the potential role of gemcitabine induction plus maintenance therapy in this setting. MATERIALS AND METHODS Eligible patients had recurrent nonmuscle invasive bladder cancer, stage Tis (carcinoma in situ), T1, Ta high grade or multifocal Ta low grade after at least 2 prior courses of bacillus Calmette-Guérin. Patients were treated with 2 gm gemcitabine in 100 cc normal saline intravesically weekly × 6 and then monthly to 12 months. Cystoscopy and cytology were performed every 3 months, with biopsy at 3 months and then as clinically indicated. Initial complete response was defined as negative cystoscopy, cytology and biopsy at 3 months. RESULTS A total of 58 patients were enrolled in the study and 47 were evaluable for response. Median patient age was 70 years (range 50 to 88). Of the evaluable patients 42 (89%) had high risk disease, including high grade Ta in 12 (26%), high grade T1 in 2 (4%) and carcinoma in situ in 28 (60%) with or without papillary lesions. At the initial 3-month evaluation 47% of patients were free of disease. At 1 year disease had not recurred in 28% of the 47 patients, all except 2 from the high risk group, and at 2 years disease had not recurred in 21%. CONCLUSIONS Intravesical gemcitabine has activity in high risk nonmuscle invasive bladder cancer and offers an option for patients with recurrence after bacillus Calmette-Guérin who are not suitable for cystectomy. However, less than 30% of patients had a durable response at 12 months even with maintenance therapy.

Renal Cell Carcinoma and End Stage Renal Disease

PURPOSE Patients with ESRD secondary to acquired renal cystic disease have been reported to have a higher incidence of RCC than the general population. We examined the clinical and pathological significance of incidental renal masses in patients with ESRD. MATERIALS AND METHODS From January 1994 to July 2000, 852 consecutive patients with ESRD who were being considered for renal transplantation at University of Mississippi Medical Center were evaluated with renal ultrasound as part of assessment for possible kidney transplantation. Those patients with ultrasound suspicious for a malignant renal lesion were further evaluated with CT of the abdomen with and without intravenous contrast medium. Any patient with CT findings suspicious for RCC was recommended to undergo radical nephrectomy before kidney transplantation. RESULTS A total of 19 patients had CT criteria for a possible malignant renal lesion. Seven patients had Bosniak class 3 renal cysts and 12 patients had solid, enhancing renal masses. Of the patients 17 underwent radical nephrectomy. On pathological examination 14 patients had RCC with a 1.64% prevalence in the population screened. Mean Fuhrman nuclear grade in our patients was 2.45. CONCLUSIONS RCC in patients with ESRD are of clinical significance, considering the size, grade, histology and pathological stage of these tumors. The higher prevalence of clinically significant RCC in patients with ESRD as well as the risk of cancer progression while patients are on immunosuppressive medications justifies screening for RCC in patients with ESRD who are awaiting renal transplantation.

Culture-Independent Microbiological Analysis of Foley Urinary Catheter Biofilms

Background Prevention of catheter-associated urinary tract infection (CAUTI), a leading cause of nosocomial disease, is complicated by the propensity of bacteria to form biofilms on indwelling medical devices [1], [2], [3], [4], [5]. Methodology/Principal Findings To better understand the microbial diversity of these communities, we report the results of a culture-independent bacterial survey of Foley urinary catheters obtained from patients following total prostatectomy. Two patient subsets were analyzed, based on treatment or no treatment with systemic fluoroquinolone antibiotics during convalescence. Results indicate the presence of diverse polymicrobial assemblages that were most commonly observed in patients who did not receive systemic antibiotics. The communities typically contained both Gram-positive and Gram-negative microorganisms that included multiple potential pathogens. Conclusion/Significance Prevention and treatment of CAUTI must take into consideration the possible polymicrobial nature of any particular infection.

Alvimopan, a peripherally acting μ-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial.

PURPOSE We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial. MATERIALS AND METHODS Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs. Differences in base case mean costs between the study cohorts for total postoperative ileus related costs (hospital days, study drug, nasogastric tubes, postoperative ileus related concomitant medication and postoperative ileus related readmissions) and total combined costs (postoperative ileus related, laboratory, electrocardiograms, nonpostoperative ileus related concomitant medication and nonpostoperative ileus related readmission) were evaluated by probabilistic sensitivity analysis using a bootstrap approach. RESULTS Mean hospital stay was 2.63 days shorter for alvimopan than placebo (mean±SD 8.44±3.05 vs 11.07±8.23 days, p=0.005). Use of medications or interventions likely intended to diagnose or manage postoperative ileus was lower for alvimopan than for placebo, eg total parenteral nutrition 10% vs 25% (p=0.001). Postoperative ileus related health care costs were

Angiomyolipoma with vena caval extension.

2,340 lower for alvimopan and mean total combined costs were decreased by

Differential effects of valproic acid on growth, proliferation and metastasis in HTB5 and HTB9 bladder cancer cell lines

2,640 per patient for alvimopan vs placebo. Analysis using a 10,000-iteration bootstrap approach showed that the mean difference in postoperative ileus related costs (p=0.04) but not total combined costs (p=0.068) was significantly lower for alvimopan than for placebo. CONCLUSIONS In patients treated with radical cystectomy alvimopan decreased hospitalization cost by reducing the health care services associated with postoperative ileus and decreasing the hospital stay.

Potentiation of mitomycin C tumoricidal activity for transitional cell carcinoma by histone deacetylase inhibitors in vitro.

69-year-old woman of the Jehovah’s Witness faith was found to have a mass on a computed tomography bone density scan done for osteoporosis. Computed tomography demonstrated a 10-cm right renal mass with a tumor thrombus extending to the level of the hepatic veins (Fig. 1). Both the computed tomography and magnetic resonance imaging scans demonstrated fat within the tumor, consistent with an angiomyolipoma or a liposarcoma (Fig. 2). No metastatic disease was evident. A right radical nephrectomy was performed with a retroperitoneal lymphadenectomy and level II thrombectomy using a thoracoabdominal approach 1 (Fig. 3). Erythropoietin was given preoperatively, and her starting hematocrit was 50%. Vascular control was obtained intraoperatively by mobilizing the liver off the inferior vena

Altered expression and modulation of the two-pore-domain (K2P) mechanogated potassium channel TREK-1 in overactive human detrusor

High grade invasive bladder cancer is a leading cause of cancer deaths and treatment options are limited for this type of cancer. Recent studies have reported anticancer effects of valproic acid in many cancers and also in superficial bladder cancer. Acute valproic acid administration suppressed cell proliferation in a time- and dose-dependent manner in two muscle-invasive human bladder cancer cell lines (HTB5 and HTB9), with accompanying G1 phase cell cycle arrest. A significant decrease in colony formation ability and invasiveness was seen with valproic acid treatment though the effectiveness varied with cell type. Our results suggest a role for valproic acid in inhibiting growth and invasion of muscle-invasive bladder cancer.