Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis. OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies (including antibiotics, probiotics, and other agents) for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, EMBASE and the Cochrane Library from inception to October 2014. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for ulcerative colitis were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was the proportion of patients with clinical improvement or remission of pouchitis in patients with acute or chronic pouchitis, or the proportion of patients with no episodes of pouchitis after IPAA. The proportion of patients who developed at least one adverse event was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Thirteen studies (517 participants) were included in the review. Four studies assessed treatment of acute pouchitis. One study (16 participants) compared ciprofloxacin and metronidazole; another (26 participants) compared metronidazole to budesonide enemas; another (18 participants) compared rifaximin to placebo; and the fourth study (20 participants) compared Lactobacillus GG to placebo. Four studies assessed treatment of chronic pouchitis. One study (19 participants) compared glutamine to butyrate suppositories; another (40 participants) compared bismuth enemas to placebo; and two studies (76 participants) compared VSL#3 to placebo. Five studies assessed prevention of pouchitis. One study (40 participants) compared VSL#3 to placebo; another (28 participants) compared VLS#3 to no treatment; one study (184 participants) compared allopurinol to placebo; another (12 participants) compared the probiotic Bifidobacterium longum to placebo; and one study (38 participants) compared tinidazole to placebo. Three studies were judged to be of high quality. Two studies were judged to be low quality and the quality of the other studies was unclear. Treatment of acute pouchitis: The results of one small study (16 participants) suggest that ciprofloxacin may be more effective than metronidazole for the treatment of acute pouchitis. One hundred per cent (7/7) of ciprofloxacin patients achieved remission at two weeks compared to 33% (3/9) of metronidazole patients. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to high risk of bias (no blinding) and very sparse data (10 events). There was no difference in the proportion of patients who had at least one adverse event (RR 0.18, 95% CI 0.01 to 2.98). Adverse events included vomiting, dysgeusia or transient peripheral neuropathy. There were no differences between metronidazole and budesonide enemas in terms of clinical remission, clinical improvement or adverse events. Adverse events included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. There were no differences between rifaximin and placebo in terms of clinical remission, clinical improvement, or adverse events. Adverse events included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. There was no difference in clinical improvement between Lactobacillus GG and placebo. The results of these studies are uncertain due to very low quality evidence. Treatment of chronic pouchitis: A pooled analysis of two studies (76 participants) suggests that VSL#3 may be more effective than placebo for maintenance of remission. Eighty-five per cent (34/40) of VLS#3 patients maintained remission at 9 to 12 months compared to 3% (1/36) of placebo patients (RR 20.24, 95% CI 4.28 to 95.81). A GRADE analysis indicated that the quality of evidence supporting this outcome was low due to very sparse data (35 events). Adverse events included abdominal cramps, vomiting and diarrhea. There was no difference in effectiveness between glutamine and butyrate suppositories for maintenance of remission. There was no difference in clinical improvement or adverse event rates between bismuth carbomer foam enemas and placebo. Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. The results of these studies are uncertain due to very low quality evidence. Prevention of pouchitis: The results of one small study (40 participants) suggest that VSL#3 may be more effective than placebo for prevention of pouchitis. Ninety per cent (18/20) of VSL#3 patients had no episodes of acute pouchitis during the 12 month study compared to 60% (12/20) of placebo patients (RR 1.50, 95% CI 1.02 to 2.21). A GRADE analysis indicated that the quality of evidence supporting this outcome was low due to very sparse data (30 events). Another small study (28 participants) found that VLS#3 was not more effective than no treatment for prevention of pouchitis. Bifidobacterium longum, allopurinol and tinidazole were not more effective than placebo for prevention of pouchitis. The results of these studies are uncertain due to very low quality evidence. AUTHORS' CONCLUSIONS: For acute pouchitis, very low quality evidence suggests that ciprofloxacin may be more effective than metronidazole. For chronic pouchitis, low quality evidence suggests that VSL#3 may be more effective than placebo for maintenance of remission. For the prevention of pouchitis, low quality evidence suggests that VSL#3 may be more effective than placebo. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

Bariatric surgery in the prevention of obesity-associated cancers: mechanistic implications.

Obesity is associated with an increased risk of at least 13 different cancers, as well as worse cancer outcomes and increased cancer mortality. As rates continue to rise both in the United States and worldwide, obesity is poised to become the leading lifestyle-related risk factor for cancer. Currently, the most effective treatment for patients with severe obesity is bariatric surgery. Multiple cohort studies have demonstrated a consistent >30% decreased risk of cancer incidence in women, but not men, following bariatric surgery. However, the physiologic mechanisms driving obesity-associated cancer and the cancer-protective effect of bariatric surgery are not clearly defined. In this review, we highlight emerging concepts in the mechanistic understanding of obesity-associated cancer. Evidence from both human studies and preclinical animal models suggest that obesity drives carcinogenesis through dysregulation of systemic metabolism, immune dysfunction, and an altered gut microbiome. Additionally, we present related findings to suggest that bariatric surgery may disrupt and even reverse many of these mechanisms. Finally, we discuss the use of preclinical bariatric surgery animal models in the study of cancer biology. The prevention of cancer is emerging as an important indication for bariatric surgery. Elucidating the mechanisms through which bariatric surgery limits carcinogenesis is critical to developing a variety of interventions that intercept obesity-driven cancer.

Obesity and breast cancer: Preventive and therapeutic possibilities for bariatric surgery.

Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.

Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort.

BACKGROUND: Bariatric surgery reduces cancer risk in populations with obesity. It is unclear if weight loss alone or metabolic changes related to bariatric surgery cause this effect. OBJECTIVE: We evaluated the relationship between surgical weight loss and serum biomarker changes with incident cancer in a bariatric surgery cohort. SETTING: Ten U.S. clinical facilities. METHODS: The Longitudinal Assessment of Bariatric Surgery 2 (LABS-2) is a prospective multicenter cohort (n = 2458, 79% female, mean age = 46). We evaluated weight and serum biomarkers, measured preoperatively and 1 year postoperatively, as predictors for incident cancer. Associations were determined using Cox proportional hazards models adjusting for weight loss, age, sex, education, and smoking history. RESULTS: Over 8759 person-years of follow-up, 82 patients reported new cancer diagnosis (936 per 100,000 person-years, 95% confidence interval [CI]: 749-1156). Cancer risk was decreased by approximately 50% in participants with 20% to 34.9% total weight loss (TWL) compared with <20% TWL (hazard ratio [HR] = .49, 95%CI: .29-.83). Reduced cancer risk was observed with percent decrease from baseline for glucose (per 10%, HR = .94, 95%CI: .90-.99), proinsulin (per 20%, HR = .95, 95%CI: .93-.98), insulin (per 30%, HR = .97, 95%CI: .96-.99), and leptin (per 20%, HR = .81, 95%CI: .68-.97), and per 15% percent increase in ghrelin (HR = .94, 95%CI: .29-.83). CONCLUSIONS: After bariatric surgery, cancer risk is reduced >50% when weight loss exceeds 20% TWL compared with patients with <20% TWL. Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk.

Weight loss and co-morbidity resolution between different races and ethnicities after gastric bypass.

BACKGROUND: Several studies have demonstrated that minorities and Hispanic ethnicities have disproportionally greater burden of morbid obesity in the United States. However, the majority of bariatric procedures are performed in the non-Hispanic white population. OBJECTIVES: The objective of this study was to investigate the weight loss and remission of obesity-related co-morbidities based on race and ethnicity. SETTING: The Longitudinal Assessment of Bariatric Surgery prospective, multicenter, observational study was used to collect patients from 10 different health centers across the United States. METHODS: Retrospective analysis of a prospective, multicenter, observational study over a 5-year follow-up. RESULTS: All patients who underwent primary gastric bypass and provided racial/ethnic information were included in the study (n = 1695). Regardless of race or ethnicity, total weight loss was maintained over a 5-year follow-up, which included 87% of the original cohort. However, whites had on average 1.94% higher adjusted total weight loss compared with blacks (P < .0001). After adjusting for confounders there were no significant differences in resolution of co-morbidities, including diabetes. CONCLUSION: All patients regardless of race or ethnicity have significant and sustained total weight loss and resolution of co-morbidities after gastric bypass at 5-year follow-up.

Psychosocial Factors Are Associated with Quality of Life After Laparoscopic Antireflux Surgery.

BACKGROUND: Laparoscopic antireflux surgery (LARS) is the gold standard treatment for refractory gastroesophageal reflux disease (GERD). Traditional surgical outcomes following LARS are well described, but limited data exist regarding patient-reported outcomes. We aimed to identify preoperative characteristics that were independently associated with a high GERD health-related quality of life (GERD-HRQL) following LARS. METHODS: Clinical data from our single institution foregut surgery database were used to identify all patients with GERD who underwent primary LARS from June 2010 to November 2015. Electronic health record data were reviewed to extract patient characteristics, diagnostic study characteristics, and operative data. Postoperative GERD-HRQL data were obtained through telephone follow-up. Variables hypothesized a priori to be associated with high GERD-HRQL after LARS, which were significant at P ≤ .2 on bivariate analysis, were entered into a multivariable linear regression model with GERD-HRQL as the outcome. RESULTS: The study included 248 patients; 69.0% were female, 56.9% were married, and 58.1% had concurrent atypical symptoms. The most commonly performed fundoplications were Nissen (44.8%), Toupet (41.3%), and Dor (14.1%), respectively. The median follow-up interval was 3.4 years. The telephone response rate was 60.1%. GERD-HRQL scores improved from 24.8 (SD ±11.4) preoperatively to 3.0 (SD ±5.9) postoperatively. 79.9% of patients were satisfied with their condition at follow-up. On multivariable analysis, being married (P = .04) and absence of depression (P = .02) were independently associated with a higher postoperative QoL. CONCLUSIONS: Strong social support and psychiatric well-being appear to be important predictors of a higher QoL following LARS. Optimizing social support and treating depression preoperatively and postoperatively may improve QoL outcomes for LARS patients.

Timing of bariatric surgery for severely obese adolescents: a Markov decision-analysis.

PURPOSE: Although controversial, bariatric surgery is increasingly being performed in adolescents. We developed a model to simulate the effect of timing of gastric bypass in obese adolescents on quantity and quality of life. METHODS: A Markov state-transition model was constructed comparing two treatment strategies: gastric bypass surgery at age 16 versus delayed surgery in adulthood. The model simulated a hypothetical cohort of adolescents with body mass index of 45kg/m(2). Model inputs were derived from current literature. The main outcome measure was quality and quantity of life, measured using quality-adjusted life-years (QALYs). RESULTS: For females, early gastric bypass surgery was favored by 2.02 QALYs compared to delaying surgery until age 35 (48.91 vs. 46.89 QALYs). The benefit was even greater for males, where early surgery was favored by 2.9 QALYs (48.30 vs. 45.40 QALYs). The absolute benefit of surgery at age 16 increased; the later surgery was delayed into adulthood. Sensitivity analyses demonstrated that adult surgery was favored only when the values for adverse events were unrealistically high. CONCLUSIONS: In our model, early gastric bypass in obese adolescents improved both quality and quantity of life. These findings are useful for surgeons and pediatricians when counseling adolescents considering weight loss surgery.

Epidural analgesia versus intravenous patient-controlled analgesia following minimally invasive pectus excavatum repair: a systematic review and meta-analysis.

BACKGROUND/PURPOSE: The minimally invasive pectus excavatum repair (MIPER) is a painful procedure. The ideal approach to postoperative analgesia is debated. We performed a systematic review and meta-analysis to assess the efficacy and safety of epidural analgesia compared to intravenous Patient Controlled Analgesia (PCA) following MIPER. METHODS: We searched MEDLINE (1946-2012) and the Cochrane Library (inception-2012) for randomized controlled trials (RCT) and cohort studies comparing epidural analgesia to PCA for postoperative pain management in children following MIPER. We calculated weighted mean differences (WMD) for numeric pain scores and summarized secondary outcomes qualitatively. RESULTS: Of 699 studies, 3 RCTs and 3 retrospective cohorts met inclusion criteria. Compared to PCA, mean pain scores were modestly lower with epidural immediately (WMD -1.04, 95% CI -2.11 to 0.03, p=0.06), 12 hours (WMD -1.12; 95% CI -1.61 to -0.62, p<0.001), 24 hours (WMD -0.51, 95%CI -1.05 to 0.02, p=0.06), and 48 hours (WMD -0.85, 95% CI -1.62 to -0.07, p=0.03) after surgery. We found no statistically significant differences between secondary outcomes. CONCLUSIONS: Epidural analgesia may provide superior pain control but was comparable with PCA for secondary outcomes. Better designed studies are needed. Currently the analgesic technique should be based on patient preference and institutional resources.