Hadley Wyre

Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial

UNLABELLED After radical cystectomy (RC), patients are at risk for complications including infections. The expansion of myeloid-derived suppressor cells (MDSCs) after surgery may contribute to the lower resistance to infection. Immune response and postoperative complications were compared in men consuming either specialized immunonutrition (SIM; n=14) or an oral nutrition supplement (ONS; n=15) before and after RC. MDSC count (Lin- CD11b+ CD33+) was significantly different between the groups over time (p=0.005) and significantly lower in SIM 2 d after RC (p<0.001). MDSC count expansion from surgery to 2 d after RC showed a weak association with an increase in infection rate 90 d after surgery (p=0.061). Neutrophil:lymphocyte ratio was significantly lower in SIM compared with ONS 3h after the first incision (p=0.039). Participants receiving SIM had a 33% reduction in postoperative complication rate (95% confidence interval [CI], 1-64; p=0.060) and a 39% reduction in infection rate (95% CI, 8-70; p=0.027) during late-phase recovery. The small sample size limits the study findings. PATIENT SUMMARY Results show that the immune response to surgery and late infection rates differ between radical cystectomy patients receiving specialized immunonutrition versus oral nutrition supplement in the perioperative period. TRIAL REGISTRATION ClinicalTrials.gov NCT01868087.

Alvimopan in an Enhanced Recovery Program Following Radical Cystectomy.

Abstract Background: Radical cystectomy (RC) carries a high complication rate, including post-operative ileus. Alvimopan is an FDA approved peripherally acting μ-opioid receptor antagonist that has shown favorable results for improved recovery of gastro-intestinal function resulting in decreased hospital length of stay. Many enhanced recovery pathways (ERP) have been published demonstrating improved outcomes with decreased hospital stay and morbidity. Objective: We evaluated the addition of alvimopan to an ERP in patients undergoing RC. Methods: Patients undergoing RC at our institution during the implementation phase of alvimopan to our established ERP were retrospectively reviewed. Effect of alvimopan as it related to the use of nasogastric tubes, time to initiation of regular diet, and length of hospital stay was assessed using Chi-squared and Student’s T-tests. Linear regression was performed for univariate analysis and binary logistic regression was performed as a multivariate assessment of the effect of alvimopan. Results: Between July 2011 and January 2013, 80 patients were identified who underwent RC under the ERP (34 alvimopan and 46 standard care). Age, sex, neoadjuvant chemotherapy, surgical technique (open vs. robotic), and type of urinary diversion were not different between groups. Alvimopan was associated with a reduction in mean time to regular diet (5.3 vs 4.1 days, p <  0.01) and a reduction in mean length of hospital stay (6.9 vs 5.7 days, p = 0.01). After controlling for other variables, alvimopan usage predicted for shorter time to regular diet and total hospital stay. Conclusions: Alvimopan may help to improve time to regular diet and decrease hospital stay in patients on an enhanced recovery pathway.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial

Purpose: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short‐term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. Materials and Methods: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1‐Th2 balance, plasma interleukin‐6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x‐ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. Results: In the specialized immunonutrition group there was a 54.3% average increase in the Th1‐Th2 balance according to the tumor necrosis factor‐&agr;‐to‐interleukin‐13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1‐Th2 balance decreased 4.8%. The change in the Th1‐Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin‐6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. Conclusions: Th1‐to‐Th2 ratios, peak interleukin‐6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T‐helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

The July Effect in Radical Cystectomy: Mortality, Morbidity, and Efficiency

Background: The “July effect” is the potential effect that new and recently promoted residents have on patient care during the first months of the academic year. Literature suggests that the July effect may worsen patient outcomes and lead to systemic inefficiencies. Objective: We evaluate the July effect on mortality, morbidity, and efficiency outcomes in patients undergoing radical cystectomy. Methods: A chart review was performed in patients who underwent radical cystectomy between January 2008 and April 2012. Demographic information was abstracted from patient charts and outcomes compared between operations performed in July, September, and November (first month of each resident’s university rotation) to the remainder of the year. Outcomes of interest included mortality, complications, and markers of efficiency (operative time, length of hospital stay, and estimated blood loss). Results: Two hundred and fifty one patients were included in the analysis. There were no major differences in mortality or morbidity between the July, September, November group and the rest of the year. Multivariable analysis demonstrates a trend for operations performed in the months of July, September, and November to be associated with longer OR times 2.06 (0.99–4.27), p = 0.053. Length of hospital stay and estimated blood loss were no different between the two groups. Conclusions: These data demonstrate no increase in mortality or morbidity during the early academic period. Additionally, while there is a trend for OR time to be longer in the early group, length of hospital stay and estimated blood loss were no different. These data may be used as an impetus to continue to investigate technical/clinical teaching practices, strategies to assess resident progression, and to initiate protocols to support residents early in the academic year in efforts to prevent inefficiencies.

Postoperative Outcomes After Radical Cystectomy in Patients With Prior Pelvic Radiation

OBJECTIVE To compare complication rates, perioperative outcomes, and survival after radical cystectomy (RC) in patients with prior abdominal or pelvic radiation therapy (RT) vs those without an RT history. MATERIALS AND METHODS We retrospectively reviewed patients undergoing RC for urothelial carcinoma between January 2008 and January 2016. Patients were stratified by receipt of RT, and differences in complications (any, minor, and major) at 30 and 90 days, as well as estimated blood loss, length of surgery, length of hospital stay, and pathologic stage, were compared. Recurrence-free, cancer-specific, and overall survival were compared using the Kaplan-Meier method and log-rank test. RESULTS We identified 518 patients who underwent RC between 2008 and 2016. Of these patients, 55 (11%) had a history of RT. There were no significant differences in complication rates (66% vs 69%, P= .80) between patients who did not and patients who did have a history of RT. Similarly, there were no differences in any perioperative or pathologic outcome by receipt of prior RT (all P>.05). Meanwhile, at a median follow-up of 26 (interquartile range 13-46) months among patients alive at last follow-up, no differences in survival were observed by prior RT (P= .08). CONCLUSION Among patients with a history of prior abdominal or pelvic RT treated at a tertiary referral center, there was no difference in complication rates, perioperative, or pathologic outcomes. Importantly, no differences in survival were noted by prior RT receipt. Therefore, our data support the use of RC, when indicated, in patients with a prior history of abdominal or pelvic RT.

Effects of Smoking, Alcohol, and Exercise on Prostate Cancer

Abstract Multiple studies have been undertaken to examine the causes and risk factors of developing prostate cancer. Smoking, alcohol, and physical activity are three lifestyle behaviors that have been extensively examined as potentially modifiable risk factors. The results of studies on smoking and overall prostate cancer risk are conflicting, with no clear association identified. However, the data more strongly support an association between smokers and former smokers and the increased risk of developing advanced or fatal prostate cancer. As with smoking, the results of alcohol consumption on the subsequent development of incident and advanced/fatal prostate cancer are mixed. Interestingly, both the Prostate Cancer Prevention Trial and the REDUCE trial were analyzed and there appears to be an interaction with increased alcohol intake and the chemopreventative effect of finasteride and dutasteride. Physical activity on the other hand does appear to have a relationship with prostate cancer risk. The majority of studies have identified an inverse relationship between physical activity, either recreational or occupational, and the risk of developing incident and advanced/fatal prostate cancer.

MP64-20 COMPLETE PATHOLOGIC RESPONSE TO NEOADJUVANT CHEMOTHERAPY FOR BLADDER CANCER: THE EFFECT OF PRE-TREATMENT CLINICAL STAGE

INTRODUCTION AND OBJECTIVES: We evaluated patients followed with non-muscle invasive, nested variant of urothelial carcinoma and compared progression and survival outcomes to patients with pure urothelial carcinoma. METHODS: We identified 4086 patients with bladder cancer who presented with pTa, pTis, or pT1 at diagnosis. Among this cohort, there were 3897 patients with pure urothelial carcinoma and 92 patients were found to have nested variant features at some point during followup. In order to assess whether there is a difference in progression-free survival (PFS) between NMIBC patients with pure urothelial carcinoma and those with nested features, we utilized multivariable Cox proportional hazards models adjusting for gender, age and tumor stage (pT1 vs pTa/pTis) at diagnosis. A univariate Cox proportional hazards model was used to assess difference in overall survival (OS) based on nested or pure urothelial carcinoma histology. RESULTS: On univariate analysis, nested variant was found to be significantly associated with poorer PFS (HR 6.25; 95% C.I. 4.52, 8.65; p < 0.0001). Hazard ratios were similar after adjusting for standard predictors on multivariable analysis, (HR: 4.12; 95% C.I. 2.98, 5.69; p < 0.0001). Figure 1 displays the PFS curves for UC vs. nestedfeatures estimated from our multivariable Cox proportional hazard models based on the covariate values of the average patient with nested features: 65 year old, male patient with a diagnostic tumor stage of pT1. On univariate analysis, having nested variant was found to be significantly associated with poorer OS (HR 1.97; 95% C.I. 1.45, 2.67; p < 0.0001). CONCLUSIONS: Non-muscle invasive, nested variant of urothelial carcinoma is associated with significantly poorer PFS and OS compared with pure urothelial carcinoma, suggesting that these patients should be considered for more aggressive surveillance and earlier treatment.