Multi-institutional outcomes and cost effectiveness of using alvimopan to lower gastrointestinal morbidity after cystectomy and urinary diversion.

INTRODUCTION: Radical cystectomy is associated with significant morbidity and cost, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized-control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan and cost benefit associated. MATERIALS AND METHODS: Between January 2008 and October 2012, 80 patients underwent radical cystectomy with urinary diversion at two institutions. Forty-two patients in our study did not receive alvimopan preoperatively. Thirty-eight patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications and estimated cost of hospitalization were evaluated. RESULTS: Times to first flatus (3.1 days versus 4.7 days, p < 0.01, 95% CI 0.96-2.24) and bowel movement (3.9 days versus 4.9 days, p < 0.01, 95% CI 0.45-1.55) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 days versus 5.5 days, p < 0.01, 95% CI 0.70-2.10), regular diet (5.2 days versus 6.3 days, p < 0.01, 95% CI 0.39-1.81) and hospital discharge (6.1 days versus 7.7 days, p = 0.04, 95% CI 0.01-3.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 26.2%, p < 0.01). With an approximate average cost of alvimopan administration $825 per hospitalization, the average cost benefit of administration over control was $1515 per hospitalization. The cost benefit was mainly a result of a shorter inpatient hospitalization and lack of gastrointestinal morbidity which accumulated a majority of the difference. CONCLUSION: In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of post-operative ileus in patients following radical cystectomy and urinary diversion.

Evaluation the cytotoxic effect of Fe3O4@Glu-Gingerol on lung adenocarcinoma cell line (A549) with biological mechanisms.

The use of nanotechnology products with supermagnetic properties for targeted delivery of drugs has gained attention recently. Due to the anticancer features of Gingerol, the major phenolic compound from Ginger, this study aims to prepare Fe3O4@Glucose-Gingerol nanoparticles (NPs) and investigate their anticancer potential in a lung adenocarcinoma cell line. The physical and chemical features of the nanoparticles were investigated by FT-IR, XRD, zeta potential, DLS, EDS mapping, VSM, and electron microscope imaging. Cytotoxic effects of the nanoparticles for the A549 (lung adenocarcinoma) and MRC-5 (normal) cell lines was investigated by MTT assay. Furthermore, the effects of Fe3O4@Glucose-Gingerol nanoparticles on the expression of the CASP8, BAX, and BCL2 genes and the activity of Caspase 3 were characterized. The flow cytometry assay (annexin V/PI) was employed to find out the percentage of apoptotic cells. The Fe3O4@Glu-Gingerol NPs were spherical (42-67 nm), without elemental impurity, and with surface charge, DLS size, and magnetic saturation of -47.7 mV, 154 nm, and 35 emu/g, respectively. Fe3O4@Glu-Gingerol NPs showed a remarkable greater toxicity in the A549 cells than normal cell line with the 50 % inhibition concentration (IC50) of 190 and 554 µg/mL, respectively. Treatment of lung adenocarcinoma cells with the Fe3O4@Glu-Gingerol NPs led to an increase in cell apoptosis from 4.6 to 39.48 %. Also, the CASP8 and BAX genes were upregulated by 2.49 and 2.8 folds, respectively, while a downregulation by 0.75 folds was noticed for the BCL2. Moreover, apoptotic features were observed in Fe3O4@Glu-Gingerol NPs treated cells by Hoechst staining, and activation of Caspase 3 by 2.8 folds. This study revealed that the Fe3O4@Glu-Gingerol NPs have antiproliferative effects on the lung adenocarcinoma cell line by activation of intrinsic and extrinsic apoptosis that is a promising feature in cancer treatment.

Alvimopan provides rapid gastrointestinal recovery without nasogastric tube decompression after radical cystectomy and urinary diversion.

INTRODUCTION: Radical cystectomy is associated with significant morbidity, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan. MATERIALS AND METHODS: Between January 2008 and August 2011, 50 consecutive patients underwent radical cystectomy with urinary diversion at our institution. The first 27 patients in our study did not receive alvimopan preoperatively. The latter 23 patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications were evaluated. RESULTS: Times to first flatus (3.1 versus 5.6 days, p < 0.001, 95% CI 1.66-3.26) and bowel movement (3.8 versus 6.0 days, p < 0.001, 95% CI 1.35-2.99) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 versus 6.3 days, p < 0.001, 95% CI 1.20-3.12), regular diet (5.7 versus 7.3 days, p = 0.023, 95% CI 0.57-2.63) and hospital discharge (7.4 versus 9.5 days, p = 0.04, 95% CI 0.03-4.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 25.9%, p = 0.012). CONCLUSION: In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of postoperative ileus in patients following radical cystectomy and urinary diversion.

Synthesize of Bi2O3/Gln-TSC nanoparticles and evaluation of their toxicity on prostate cancer cells and expression of CASP8, BAX, and Bcl-2 genes.

Due to the high prevalence and considerable increase of prostate cancer, finding novel therapeutic compounds for the treatment of prostatic cancer has been the goal of many researches. In this study, we aimed to fabricate the Bismuth oxide (Bi2O3) NPs, functionalized with glutamine (Gln) and conjugated with Thiosemicarbazide (TSC). Then, the anticancer mechanism of the synthesized NPs was investigated using the cellular and molecular tests including MTT assay, Flow cytometry, Caspase-3 activity assay, Hoechst staining and Real Time PCR. The FT-IR and XRD assays confirmed the identity of the synthesized Bi2O3/Gln-TSC NPs. The size range of the synthesized spherical particles was 10-60 nm and the zeta potential was - 23.8 mV. The purity of the NPs was confirmed by EDX-mapping analysis. The Bi2O3/Gln-TSC was considerably more toxic for prostate cancer cells than normal human cells and the IC50 was calculated 35.4 and 305 µg/mL, respectively. The exposure to the NPs significantly increased the frequency of apoptotic cells from 4.7 to 75.3%. Moreover, the expression of the CASP8, BAX, and Bcl-2 genes after exposure to the NPs increased by 2.8, 2.3, and 1.39 folds. Treating the cancer cells with Bi2O3/Gln-TSC increased the activity of the Caspase-3 protein and apoptotic morphological features were observed by Hoechst staining in the treated cells. This work showed that Bi2O3/Gln-TSC has considerable cytotoxicity for prostate cancer cells and could inducing both intrinsic and extrinsic pathways of apoptosis.

Incidence of postembolization syndrome after complete renal angioinfarction: a single-institution experience over four years.

OBJECTIVE: Renal angioinfarction (RAI) has been used for various indications in the management of renal tumors. While historically used for palliation of local symptoms (pain or hematuria), this technique has theoretical use in facilitating radical nephrectomy by allowing early ligation of the renal vein, decreasing blood loss and creating edema in resection planes. A common impediment to embolization is the development of postembolization syndrome (PES), which has been reported to have an incidence as high as 89%. This study reports the authors' experience with RAI as a safe palliative and adjunctive procedure over 4 years. MATERIAL AND METHODS: From 2008 to 2011, 113 patients underwent complete RAI at Washington Hospital Center for palliative or adjunctive therapy by an interventional radiologist. Procedures were performed in a radiology suite using mild sedation with vascular access obtained by femoral artery puncture. RAI was performed by subsegmental injection of polyvinyl alcohol particles. RESULTS: All 113 patients underwent successful RAI with confirmation of total arterial flow ablation via postprocedure arteriogram: 38 underwent embolization for preoperative adjunctive therapy, 34 for palliation of renal mass, 36 for trauma/hemorrhage and five for symptomatic renal artery pseudoaneurysm after partial nephrectomy. PES occurred in 33 out of 75 patients (44.0%), with symptomatic PES in only two patients (2.6%). No major complications (>Clavien grade III) occurred. Thirty-eight patients were excluded from analysis as they underwent radical nephrectomy within 24 h, preventing accurate assessment of PES. CONCLUSIONS: RAI is a safe and reliable procedure for palliation of renal masses, as an adjunctive procedure for radical nephrectomy, and for conservative management of renal hemorrhage or aneurysm. PES occurs in relatively few patients, with no major complications, and should not impede clinical consideration of this procedure.

Predictors of Gleason score upgrading in a large African-American population.

PURPOSE: Gleason score from biopsy specimens is important for prostate cancer (PCa) risk stratification and influences treatment decisions. Gleason score upgrading (GSU) between biopsy and surgical pathology specimens has been reported as high as 50 % and presents a challenge in counseling low-risk patients. While recent studies have investigated predictors of GSU, populations in these studies have been largely Caucasian. We report our analysis of predictors of GSU in a large urban African-American population. METHODS: A total of 959 patients with D'Amico low-risk prostate cancer underwent radical prostatectomy at Georgetown University or Washington Hospital Center between January 2005 and July 2012. Race, age, PSA, body mass index (BMI), cancer of the prostate risk assessment (CAPRA) score, and transrectal ultrasound (TRUS) biopsy characteristics (percent of biopsy cores showing adenocarcinoma, highest percent of biopsy core involved with cancer, and measured TRUS prostate volume) were analyzed with both univariate and multivariate analyses to identify significant predictors of GSU while controlling for clinical parameters. RESULTS: Of the 959 cases, 288 (30.0 %) were upgraded on final pathologic specimen with approximately 38 % (133/355) of African-American patients experiencing GSU. BMI (P = 0.02), percent positive biopsy cores (P < 0.01) and percent of core involved with cancer (P < 0.01), increasing CAPRA score, and serum PSA were independent predictors of GSU on both uni- and multivariate regression analyses. African Americans had a 73 % increase in the incidence of GSU over other races. CONCLUSION: More than a quarter of low-risk prostate cancer patients were upgraded on final pathology in our series. Higher BMI, serum PSA, CAPRA score, percent of cores positive, and percent of cores involved were independent predictors of GSU. Individuals with those clinical parameters may harbor occult high-grade disease and should be carefully counseled on treatment decisions.

Acute segmental testicular infarction.

We report a case of segmental testicular infarction occurring in a patient with sickle cell trait. A 20-year-old African American man presented with a complaint of sudden onset, acute severe left testicular pain for 24 hours. Scrotal ultrasound revealed a hypo-echoic mass in the left testicle. The hypo-echoic area demonstrated no blood flow in Doppler mode. Because malignancy could not be excluded, the patient underwent a standard inguinal testicular exploration. A partial orchiectomy was performed with complete excision of the lesion. Pathology revealed infarcted testicular tissue with no malignancy present. Further evaluation revealed that the patient had sickle cell trait unbeknownst to him.

Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation.

Tacrolimus inhibits lymphocyte responses by blocking calcium-dependent signalling pathways important in IL-2 generation. Daclizumab, a humanized monoclonal antibody, binds with high affinity to the Tac subunit of the IL-2 receptor complex. We reasoned therefore that the absence of IL-2R should permit lower doses of tacrolimus and thereby less toxicity. Twenty-eight patients were randomized and followed for 6 months: Group 1, high dose (HD) tacrolimus (trough 12-17 ng/mL; n = 13); Group 2, low dose (LD) tacrolimus (trough 5-10 ng/mL; n = 15). All patients received daclizumab induction (2 mg/kg) on days 0 and 14, mycophenolate mofetil (2 g/d except for one patient who received 1 g) and rapid prednisone taper. Serious infections were minimal in both groups. Hospitalizations, for various reasons, were HD (n = 12) and LD (n = 6). All patients and grafts survived for the 6-month study period. There was one rejection episode in a non-compliant patient at 101 d. LD tacrolimus appears equally effective as HD tacrolimus in preventing rejection episodes and may be associated with fewer adverse events.