An integrated analysis of bile acid metabolism in humans with severe obesity.

BACKGROUND AND AIMS: Bile acids (BA) are vital regulators of metabolism. BAs are AQ6 secreted in the small intestine, reabsorbed, and transported back to the liver, where they can modulate metabolic functions. There is a paucity of data regarding the portal BA composition in humans. This study aimed to address this knowledge gap by investigating portal BA composition and the relation with peripheral and fecal BA dynamics in conjunction with the gut microbiome. APPROACH AND RESULTS: Thirty-three individuals from the BARIA cohort were included. Portal plasma, peripheral plasma, and feces were collected. BA and C4 levels were measured employing mass spectrometry. FGF19 was measured using ELISA. Gut microbiota composition was determined through metagenomics analysis on stool samples. Considerable diversity in the portal BA composition was observed. The majority (n = 26) of individuals had a 9-fold higher portal than peripheral BA concentration. In contrast, 8 individuals showed lower portal BA concentration compared with peripheral and had higher levels of unconjugated and secondary BA in this compartment, suggesting more distal origin. The altered portal BA profile was associated with altered gut microbiota composition. In particular, taxa within Bacteroides were reduced in abundance in the feces of these individuals. CONCLUSIONS: Characterization of the portal BA composition in relation to peripheral and fecal BA increased insight into the dynamics of BA metabolism in individuals with obesity. Peripheral BA composition was much more diverse due to microbial metabolism. About 24% of the portal samples was surprisingly low in total BA; the underlying mechanism requires further exploration.

Can a laparoscopic Roux-en-Y gastric bypass be safely performed by surgical residents in a bariatric center-of-excellence? The learning curve of surgical residents in bariatric surgery.

BACKGROUND: A learning curve (LC) is a graphic display of the number of consecutive procedures performed necessary to reach competence and is defined by complications and duration of surgery (DOS). There is little evidence on the LC of surgical residents in bariatric surgery. Aim of the study is to evaluate whether the laparoscopic Roux-en-Y gastric bypass (LRYGB) can be safely performed by surgical residents, to evaluate the LC of surgical residents for LRYGB and to assess whether surgical residents fit in the LC of the bariatric center which has been established by their proctors. METHODS: Records of all 3389 consecutive primary LRYGB patients, operated between December 2007 and January 2016 in a bariatric center-of-excellence in Amsterdam, were reviewed. Differences in DOS were assessed by means of a linear regression model. Differences in complications (classified as Clavien-Dindo ≥ 2) were evaluated with the χ 2 or the Fisher exact test. Cases were clustered in groups of 70 for comparison and reported for residents with ≥70 cases as primary surgeon. RESULTS: Four surgeons (S1-4) and three residents (R1-3) performed 2690 (88.2%) and 361 (11.8%) of 3051 LRYGBs, respectively. Median (IQR) DOS was 52.0 (42.0-65.0) min for S1-4 versus 53.0 (46.0-63.0) min for R1-3 (p = 0.52). The LC of R1-3 in their first 70 cases (n = 210) differs significantly from the individual (n = 70) LCs of surgeon 1, 2, and 3, with remarkably shorter DOS for the residents (adjusted p < 0.0001; p < 0.001 and p = 0.0002, respectively) and the same amount of surgical complications 5.1% (137/2690) for S1-4 versus 3.0% (11/361) for R1-3 (p = 0.089). CONCLUSION: Laparoscopic Roux-en-Y gastric bypass can be safely performed by surgical residents under supervision of experienced bariatric surgeons. Surgical residents benefit from the experience of their proctors and they fit faultlessly in the LC of the surgical team, as set out by their proctors in a large bariatric center-of-excellence.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial).

BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.

Differences in Psychological Health and Weight Loss after Bariatric Metabolic Surgery between Patients with and without Pain Syndromes.

PURPOSE: Chronic pain and obesity often co-occur, negatively affecting one another and psychological wellbeing. Pain and psychological wellbeing improve after bariatric metabolic surgery (BMS), however, it is unknown whether psychological wellbeing improves differently after weight loss between patients with and without chronic pain. We investigated whether weight loss is associated with greater psychological wellbeing and functioning change after BMS, comparing patients with and without preoperative pain syndromes. METHODS: Depression, health-related quality of life, self-esteem, self-efficacy to exercise and controlling eating behaviours, physical activity, and food cravings were measured before and 24 months after BMS among 276 patients with obesity. The presence of preoperative chronic pain syndromes was examined as a moderator for the relationship between 24-month weight loss and changes in psychological outcomes. RESULTS: Chronic pain syndromes were present among 46% of patients. Weight loss was associated with greater improvement in health-related quality of life, self-efficacy to exercise and controlling eating behaviours, self-esteem and greater amelioration in food cravings. Pain syndromes only moderated negatively the relationship between the postoperative weight loss and change in self-efficacy to control eating behaviours (b = -0.49, CI [-0.88,-0.12]). CONCLUSION: Patients with and without chronic pain showed similar improvements in weight and psychological wellbeing and behaviours after BMS. The relationship between weight loss and the improvement of self-efficacy to control eating behaviours was weaker among patients with chronic pain syndrome. Further work, measuring pain severity over time, is needed to shed light on the mechanism underlying pain and postoperative change in psychological wellbeing and weight loss.

Post-Bariatric Hypoglycemia: an Impaired Metabolic Response to a Meal.

AIMS/HYPOTHESIS: Post-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH. METHODS: We performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH. RESULTS: Out of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH. CONCLUSION: Overall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH.

Selection of patients for hepatic surgery of colorectal cancer liver metastasis based on genomic aberrations.

BACKGROUND: We investigated whether genomic aberrations in primary colorectal cancer (CRC) can identify patients who are at increased risk of developing additional hepatic recurrence after colorectal liver metastases (CLM) resection. METHODS: Primary tumour DNA from 79 CLM resected patients was analysed for recurrent copy number changes (12x135k NimbleGen(™) aCGH). The cohort was divided into three groups: CLM patients with a recurrence-free survival after hepatic resection of at least 5 years (n = 21), patients who developed intra-hepatic recurrence (n = 32), and patients who developed extrahepatic recurrence (n = 26). By contrasting the primary tumour profiles of recurrence free and the extrahepatic recurrence CLM patients, a classifier, the extra-hepatic recurrence classifier (ERC1), predictive for subsequent extrahepatic-recurrence was developed. RESULTS: The ERC1 had an accuracy of 70 % (95 % confidence interval (CI): 55-82 %, misclassification error 30 %, base error rate: 45 %). This analysis identified a region on Chromosome 12p13 as differentially aberrated between these two groups. The classifier was further optimized by contrasting the extrahepatic recurrence group with the combined group of intrahepatic and no recurrence group, resulting in an extrahepatic prognostic classifier (ERC2) able to classify patients with CLMs suitable for hepatic resection with 74 % accuracy (95 % CI: 62-83 %, misclassification error 26 %, base error rate: 32 %). CONCLUSIONS: Patients with CLM who will develop extrahepatic recurrence may be identified with ERCs based on information in the primary tumour. Risk estimates for the occurrence of extrahepatic metastases may allow a reduction of hepatic resections of colorectal liver metastases for those who are unlikely to develop extrahepatic metastases.

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency.

Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples.

Attachment style and post-bariatric surgery health behaviours: the mediating role of self-esteem and health self-efficacy.

BACKGROUND: Attachment avoidance and anxiety have been linked to overweight and poor health behaviours, yet the mechanisms that underpin the relationship between attachment and health behaviours are not fully understood. Self-esteem and self-efficacy have been found to differ between attachment styles, rendering these variables potential mediators of the relationship. This longitudinal study investigated the serial mediation between preoperative attachment and 2-year post-operative health behaviours through self-esteem and health self-efficacy. METHODS: Participants were 263 bariatric surgery patients (75.7% females, aged 47.7 ± 10.4 years, BMI 38.9 ± 3.6 kg/m2) assessed before the operation and again one and two years after the surgery. Patients completed the Experiences for Close Relationships Brief Scale, Rosenberg Self-esteem scale, Weight Efficacy Lifestyle Questionnaire, Bariatric Surgery Self-Management Questionnaire, Exercise Self-Efficacy Scale and the Exercise Behaviour Scale. RESULTS: Higher preoperative attachment anxiety and avoidance were associated with lower self-esteem one year after bariatric surgery and poorer health self-efficacy two years after the surgery. Self-esteem and health self-efficacy mediated the relationships between preoperative anxious and avoidant attachment and 2- year post-operative diet adherence and physical activity. CONCLUSIONS: Helping patients to feel more worthy and reinforcing their beliefs about their own competences could lead to higher engagement with healthy lifestyle and adherence to treatment protocols, ultimately helping patients to achieve their goals for bariatric surgery. CLINICAL TRIAL REGISTRATION: BARIA: Netherlands Trial Register: NL5837 (NTR5992) https://www.trialregister.nl/trial/5837 . Diabaria: ClinicalTrials.gov identifier (NCT number): NCT03330756.

A Prospective Study on the Diagnoses for Abdominal Pain After Bariatric Surgery: The OPERATE Study.

PURPOSE: Long-term follow-up after bariatric surgery (BS) reveals high numbers of patients with abdominal pain that often remains unexplained. The aim of this prospective study was to give an overview of diagnoses for abdominal pain, percentage of unexplained complaints, number and yield of follow-up visits, and time to establish a diagnosis. MATERIALS AND METHODS: Patients who visited the Spaarne Gasthuis Hospital, The Netherlands, between December 2020 and December 2021 for abdominal pain after BS, were eligible and followed throughout the entire episode of abdominal pain. Distinction was made between presumed and definitive diagnoses. RESULTS: The study comprised 441 patients with abdominal pain; 401 (90.9%) females, 380 (87.7%) had Roux-en-Y gastric bypass, mean (SD) % total weight loss was 31.4 (10.5), and median (IQR) time after BS was 37.0 (11.0-66.0) months. Most patients had 1-5 follow-up visits. Readmissions and reoperations were present in 212 (48.1%) and 164 (37.2%) patients. At the end of the episode, 88 (20.0%) patients had a presumed diagnosis, 183 (41.5%) a definitive diagnosis, and 170 (38.5%) unexplained complaints. Most common definitive diagnoses were cholelithiasis, ulcers, internal herniations, and presumed diagnoses irritable bowel syndrome (IBS), anterior cutaneous nerve entrapment syndrome, and constipation. Median (IQR) time to presumed diagnoses, definitive diagnoses, or unexplained complaints was 16.0 (3.8-44.5), 2.0 (0.0-31.5), and 13.5 (1.0-53.8) days (p < 0.001). Patients with IBS more often had unexplained complaints (OR 95%CI: 4.457 [1.455-13.654], p = 0.009). At the end, 71 patients (16.1%) still experienced abdominal pain. CONCLUSION: Over a third of abdominal complaints after BS remains unexplained. Most common diagnoses were cholelithiasis, ulcers, and internal herniations.

Is Adherence to Follow-Up After Bariatric Surgery Necessary? A Systematic Review and Meta-Analysis.

The association of adherence to follow-up (FU) after laparoscopic gastric bypass - and gastric sleeve with weight loss (WL) is unclear. The aim of this study was to evaluate this association. Fourteen full text articles were included in the systematic review. Eight studies were included in the meta-analysis concerning FU up to 3 years postoperatively and 3 for the FU between 3 and 10 years postoperatively. Results showed a significant association between adherence to FU 0.5 to 3 years postoperatively and percentage excess WL (%EWL) but did not demonstrate a significant association between FU > 3 years postoperatively and total WL (%TWL). In conclusion, adherence to FU may not be associated with WL and therefore stringent lifelong FU in its current form should be evaluated.

Risk Factors for Symptomatic Gallstone Disease and Gallstone Formation After Bariatric Surgery.

PURPOSE: Patients who undergo bariatric surgery are at risk for developing cholesterol gallstones. We aimed to identify risk factors that are associated with symptomatic gallstone disease and gallstone formation after bariatric surgery. MATERIALS AND METHODS: We included participants of the UPGRADE trial, a multicenter randomized placebo-controlled trial on the prevention of symptomatic gallstone disease with ursodeoxycholic acid (UDCA) after bariatric surgery. The association between patient characteristics and symptomatic gallstone disease, and gallstone formation was evaluated using logistic regression analysis. RESULTS: Of 959 patients, 78 (8%) developed symptomatic gallstone disease within 24 months. Risk factors were the presence of a pain syndrome (OR 2.07; 95% CI 1.03 to 4.17) and asymptomatic gallstones before surgery (OR 3.15; 95% CI 1.87 to 5.33). Advanced age (OR 0.95; 95% CI 0.93 to 0.97) was protective, and UDCA prophylaxis did not reach statistical significance (OR 0.64; 95% CI 0.39 to 1.03). No risk factors were identified for gallstone formation, whereas advanced age (OR 0.98; 95% CI 0.96 to 1.00), statin use (OR 0.42; 95% CI 0.20 to 0.90), and UDCA prophylaxis (OR 0.47; 95% CI 0.30 to 0.73) all reduced the risk. CONCLUSION: Young patients with a preoperative pain syndrome and/or asymptomatic gallstones before bariatric surgery are at increased risk for symptomatic gallstone disease after surgery. Whether statins, either alone or in combination with UDCA prophylaxis, can further reduce the burden of gallstones after bariatric surgery should be investigated prospectively.

A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity.

Non-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans.

Microbiome-derived ethanol in nonalcoholic fatty liver disease.

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10-5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.

Faecal Inflammatory Biomarkers and Gastrointestinal Symptoms after Bariatric Surgery: A Longitudinal Study.

BACKGROUND: Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints. METHOD: Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated. RESULTS: After RYGB, median calprotectin levels are significantly higher (>188, 104-415 µg/g) than before surgery (40, 19-78 µg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) µg/g before, and >5.9 (1.8-13.6) µg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) µg/g before and <0.23 (0.06-0.33) µg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values. CONCLUSION: Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.

Weight Loss Results and Compliance with Follow-up after Bariatric Surgery.

PURPOSE: The importance of follow-up (FU) for midterm weight loss (WL) after bariatric surgery is controversial. Compliance to this FU remains challenging. Several risk factors for loss to FU (LtFU) have been mentioned. The aim was therefore to evaluate the association between WL and LtFU 3 to 5 years postoperatively and to identify risk factors for LtFU. MATERIALS AND METHODS: A single-center cross-sectional study in the Netherlands. Between June and October 2018, patients scheduled for a 3-, 4-, or 5-year FU appointment were included into two groups: compliant (to their scheduled appointment and overall maximally 1 missed appointment) and non-compliant (missed the scheduled appointment and at least 1 overall). Baseline, surgical, and FU characteristics were collected and a questionnaire concerning socio-economic factors. RESULTS: In total, 217 patients in the compliant group and 181 in the non-compliant group were included with a median body mass index at baseline of 42.0 and 42.9 respectively. Eighty-eight percent underwent a laparoscopic Roux-en-Y gastric bypass. The median percentage total weight loss for the compliant and non-compliant groups was 30.7% versus 28.9% at 3, 29.3% versus 30.2% at 4, and 29.6% versus 29.9% at 5 years respectively, all p>0.05. Age, persistent comorbidities and vitamin deficiencies, a yearly salary <20,000 euro, no health insurance coverage, and not understanding the importance of FU were risk factors for LtFU. CONCLUSION: Three to 5 years postoperatively, there is no association between LtFU and WL. The compliant group demonstrated more comorbidities and vitamin deficiencies. Younger age, not understanding the importance of FU, and financial challenges were risk factors for LtFU.

Outcome expectation and risk tolerance in patients seeking bariatric surgery.

BACKGROUND: Average long-term outcome after laparoscopic Roux-en-Y gastric bypass is 25% total weight loss. The risk of short-term complications (leakage and bleeding), acute internal herniation, and mortality are 4.0%, 2.5%, and .2%, respectively. There is a paucity of evidence on what patients expect in terms of weight loss and to what extent surgical risks are tolerated. OBJECTIVE: To examine the patient's weight loss expectations and acceptance of the morbidity and mortality risk after primary laparoscopic Roux-en-Y gastric bypass. SETTING: Teaching hospital, Amsterdam, the Netherlands. METHODS: Two-hundred patients participated in a standardized survey after completion of an extensive multidisciplinary screening, before surgery. Weight loss expectations, naive assessment, and acceptation of risks of morbidity and mortality were addressed with standard gamble methods. RESULTS: The 200 participants (156 female, 78%) had a mean age of 45.1 years and a mean body mass index of 42.3 kg/m2. Weight loss was overestimated by 151 patients (75.5%), and 79 participants (39.5%) were disappointed with the predicted weight loss. Median accepted risks on short-term complications, acute internal herniation, and mortality were 35.8% (interquartile range, 21.0%-58.0%), 25.1% (interquartile range, 15.9%-50.8%), and 4.5% (interquartile range, 1.0%-10.0%), respectively. CONCLUSION: Patients seeking bariatric surgery seem to have unrealistic weight loss objectives and are willing to accept substantial risks to achieve these goals.

Smoking Behaviour and Beliefs About Smoking Cessation After Bariatric Surgery.

PURPOSE: Currently, bariatric surgery is the most effective intervention for treating morbid obesity and its complications. Smoking cessation is likely to improve smoking-related comorbidities and decrease postoperative complications. This study evaluated the smoking behaviour and thoughts about smoking cessation of patients more than 18 months after bariatric surgery. MATERIALS AND METHODS: A cross-sectional study was performed in patients who underwent bariatric surgery from July 2012 to December 2013. A questionnaire was used to evaluate smoking status, thoughts about the health benefits of cessation and characteristics of previous quit attempts in current and former smokers. Finally, actual bariatric surgery outcomes were evaluated in current, former and never smokers. RESULTS: Six hundred nine patients (response rate 52.0%) were included. Of them, 101 (16.6%) patients were current smokers, 239 (39.2%) former smokers and 269 (44.2%) patients were lifetime never smokers. Compared with former smokers, current smokers were less aware of the beneficial effects of smoking cessation on their general health; 66.4% of the former smokers thought smoking cessation would be much better for general health, compared with 20.6% of current smokers. Total weight loss was 2.8% higher in current smokers compared with former smokers. Actual long-term bariatric surgery outcomes were not significantly different between the groups. CONCLUSION: Despite advice to quit smoking and temporary quitting before surgery, a considerable group of bariatric surgery patients continues smoking after surgery. These patients were less aware of the beneficial effects of smoking cessation. This study emphasizes the need for better strategies to increase the number of successful cessations.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

A clinicopathologic analysis of peritoneal metastases of colorectal and appendiceal origin.

OBJECTIVE: To predict clinical outcome by classification of peritoneal metastases (PM) of colorectal or appendiceal origin. BACKGROUND: This study investigates whether standardized histological classification can predict outcome for PM of colorectal or appendiceal origin treated with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Histology of PM (n = 269) was evaluated by analysis of mitotic activity, atypia, cellularity, and mucinous component. For overall survival (OS) and disease-free survival (DFS) Cox proportional-hazard models were constructed. Covariates included tumor, patient, and treatment characteristics. RESULTS: PM could be categorized into four groups: low-grade, well-differentiated mucinous tumor (DPAM); intermediated-grade mucinous carcinoma (PMCA-i); high-grade mucinous carcinoma (PMCA); and high-grade nonmucinous carcinoma (PCA). Multivariate analysis showed that histological classification, gender, number of segments affected, completeness of cytoreduction, and HIPEC as primary treatment were significant related to OS and DFS. The 5-year OS was 64% in the DPAM group, 36% in the PMCA group, and 24% in the PCA group. Of PM originating from an appendix tumor, 29% were of non-DPAM type. Of primary colorectal tumors, 37% resulted in mucinous PM, and another 26% of PM of colorectal origin had partly mucinous histology. CONCLUSION: Histology is a significant predictive factor of OS and DFS in PM treated with surgical cytoreduction and HIPEC. Low-grade PM (DPAM) should be regarded as a separate entity because of its clearly different clinical course. High-grade mucinous PM has significant better prognosis than nonmucinous PM and should thus be distinguished.