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.

Synbiotics and Surgery: Can Prebiotics and Probiotics Affect Inflammatory Surgical Outcomes?

PURPOSE OF REVIEW: Prebiotics, probiotics, and synbiotics have received increasing attention over the years for their beneficial impact on the gut microbiome and for their systemic anti-inflammatory effects. They have also been shown to improve surgical outcomes. Here, we review the inflammatory effects of surgery as well as the data which suggests a benefit of prebiotics, probiotics, and synbiotics taken in the perioperative period. RECENT FINDINGS: Synbiotics and fermented foods may have an even greater anti-inflammatory effect than probiotics or prebiotics alone. Recent data suggest that the anti-inflammatory effects and microbiome changes brought on by prebiotics, probiotics, and synbiotics have the potential to improve surgical outcomes. We highlight the potential to alter systemic inflammation, surgical and hospital-acquired infections, colorectal cancer formation, recurrence, and anastomotic leak. Synbiotics could also impact metabolic syndrome. Prebiotics, probiotics, and especially synbiotics may be extremely beneficial when taken in the perioperative period. Even short-term gut microbiome pre-habilitation could alter surgical outcomes significantly.

All Fiber is Not Fiber.

PURPOSE OF REVIEW: Epidemiologic studies and clinical trials have demonstrated the benefits of dietary fiber. This occurs through a combination of the physiochemical properties of fiber and through microbial fermentation that occurs in the colon which result in the production of short-chain fatty acids (SCFA). The purpose of this review is to highlight the physiochemical properties of fiber that result in the range of physiologic effects and to review the literature on the health benefits of acetate, propionate, and butyrate. RECENT FINDINGS: Of the variety of properties and functions exerted by dietary fibers, the fermentability and production of SCFA's are emphasized in this review. Studies done in both animal and humans reveal the anti-obesity, anti-inflammatory, and possible anti-neoplastic roles SCFAs exert at the mucosal level. Many clinical questions remain regarding the optimal dose, type, and method of delivery of fiber to exert the desired beneficial effects. It has the potential to be used in the management of clinical symptoms, prevention of disease, and improvement in human health. Further studies to address this novel use of fiber has the potential to make a large impact in clinical practice.

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.

Reoperations after sleeve gastrectomy: a dual academic institutional experience.

BACKGROUND: Although laparoscopic sleeve gastrectomy (LSG) is the most common bariatric operation performed worldwide, patients can experience complications and poor outcomes that warrant reoperations. The incidence, indications, and outcomes of reoperations are not well understood. OBJECTIVE: To describe indications and outcomes for reoperations after LSG. SETTING: Two academic, tertiary care hospitals. METHODS: We performed a retrospective observational cohort review of institutional Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program data from 2014-2018 and reviewed charts of all reoperations after LSG. We analyzed demographics, preoperative symptoms and work-up, and postoperative outcomes. RESULTS: Fifty-seven reoperations after LSG represented 3.0% of 1965 bariatric cases performed. Most LSGs (56.1%) were performed outside our academic centers. Median time to reoperation and follow-up were 2.63 and 1.2 years, respectively. Conversion to gastric bypass was the most common reoperation (77.2%). More than half of the patients (52.6%) had multiple indications for reoperation. Reflux was the most common primary indication for reoperation (47.3%), followed by incisural strictures (20.1%), inadequate weight loss (17.5%), and leak/fistulae (12.2%). Reoperations were most successful when performed for reflux (92.5%) and oral intolerance from strictures (92%), whereas only 71.4% of leak/fistulas resolved. Surgery for inadequate weight loss resulted in total weight loss of 24.7 ± 10.1%. Complications occurred in 36.2% of cases but varied by indication. CONCLUSION: Symptoms and complications after LSG can persist, and patients may require reoperation. Reoperations can successfully treat the primary indications for reoperation and should be offered, but they have higher complication rates than initial operations.

Assessment of muscle activity and fatigue during laparoscopic surgery.

BACKGROUND: Cumulative musculoskeletal stress during operative procedures can contribute to the development of chronic musculoskeletal injury among surgeons. This is a concern in laparoscopic specialties where trainees may incur greater risk by learning poor operative posture or technique early in training. This study conducted an initial investigation of the physical stress encountered during the conduct of foregut laparoscopic surgery. METHODS: Subjects were divided into two groups based on their surgical experience level, high experience (HE), consisting of two attending surgeons, and low experience (LE), consisting of two fellow surgeons and a surgical chief resident. Nine distinct foregut laparoscopic procedures were observed for data collection within these groups. Electromyographic (EMG) activity was collected at the bilateral neck, shoulders, biceps, triceps, and lower back for each procedure. Physical workload was measured using percent reference voluntary contractions (%RVC) for each surgeon's muscle activities. Fatigue development was assessed using the median frequency of EMG data between two consecutive cases. Subjects completed a NASA-TLX survey when surgery concluded. RESULTS: LE surgeons experienced higher levels of %RVC in the lower back muscles compared to HE surgeons. LE fatigue level was also higher than HE surgeons across most muscle groups. A decrease in median frequency in six of the ten muscle groups after performing two consecutive cases, the largest decrements being in the biceps and triceps indicated fatigue development across consecutive cases for both surgeon groups. CONCLUSION: Surgeons developed fatigue in consecutive cases while performing minimally invasive surgery (MIS). HE surgeons demonstrated a lower overall physical workload while also demonstrating different patterns in muscle work. The findings from this study can be used to inform further ergonomic studies and the data from this study can be used to develop surgical training programs focused on the importance of surgeon ergonomics and minimizing occupational injury risk.

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.

Simple formulas to determine optimal subclavian central venous catheter tip placement in infants and children.

BACKGROUND/PURPOSE: Optimal central venous catheter (CVC) tip location is necessary to decrease the incidence of complications related to their use. We sought to create a practical method to reliably predict the length of catheter to insert into the subclavian vein during CVC placement in children. METHODS: We performed a retrospective review of 727 chest radiographs of children who underwent either left or right subclavian CVC placement. We measured the distance from the subclavian entry site to the to the right atrium/superior vena cava (RA/SVC) junction, following the catheter's course. We analyzed the relationship between that length and patient characteristics, including: age, gender, height, weight and body surface area (BSA). RESULTS: Two derived formulas using the BSA best correlated with the optimal subclavian CVC length. For the left subclavian vein approach, the optimal catheter length was 6.5 BSA+7 cm, and for the right subclavian vein approach it was 5 BSA+6. The use of these formulas correlated in CVC tip placement in a clinically proper location in 92.9% of smaller children and in 95.7% of larger children. CONCLUSION: The optimal length of central venous catheter to insert into the subclavian vein may be determined through the use of a simple formula using the BSA.

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.

In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-alpha.

Hepatic fibrosis occurs during most chronic liver diseases and is driven by inflammatory responses to injured tissue. Because DCs are central to modulating liver immunity, we postulated that altered DC function contributes to immunologic changes in hepatic fibrosis and affects the pathologic inflammatory milieu within the fibrotic liver. Using mouse models, we determined the contribution of DCs to altered hepatic immunity in fibrosis and investigated the role of DCs in modulating the inflammatory environment within the fibrotic liver. We found that DC depletion completely abrogated the elevated levels of many inflammatory mediators that are produced in the fibrotic liver. DCs represented approximately 25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8- fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce hepatic stellate cells, NK cells, and T cells to mediate inflammation, proliferation, and production of potent immune responses. The proinflammatory and immunogenic effects of fibrotic DCs were contingent on their production of TNF-alpha. Therefore, modulating DC function may be an attractive approach to experimental therapeutics in fibro-inflammatory liver disease.