The Evaluation of Gastric Emptying Using Nuclear Scintigraphy Compared to Three-Dimensional Multi-detector Computed Tomography (3D-MDCT) Gastric Volumetry in the Assessment of Poor Weight Loss Following Sleeve Gastrectomy.

BACKGROUND: Poor weight loss and weight regain are principal challenges following laparoscopic sleeve gastrectomy (LSG). There is a lack of standardised assessments and diagnostic tests to stratify the status post-LSG and determine whether anatomical or physiological problem exists. We aimed to compare nuclear scintigraphy gastric emptying with CT volumetric analysis of sleeve anatomy and determine the impact of anatomy on physiological function and its correlation with weight loss. MATERIALS AND METHODS: Patients greater than 12 months post-LSG were categorised into optimal weight loss (OWL) (n = 29) and poor weight loss groups (PWL) (n = 50). All patients underwent a protocolised nuclear scintigraphy and three-dimensional multi-detector computed tomography (3D-MDCT) gastric volumetry imaging. RESULTS: Post-operative % total weight loss in OWL was 26.2 ± 10.5% vs. 14.2 ± 10.7% in the PWL group (p value < 0.0001). The PWL group had significantly more delayed gastric emptying half-time than OWL (34.1 ± 18.8 vs. 19.5 ± 4.7, p value < 0.0001). Gastric emptying half-time showed statistically significant correlations with weight loss parameters (BMI; r = 0.215, p value 0.048, %EWL; r = - 0.336, p value 0.002 and %TWL; r = - 0.379, p value < 0.001). The median gastric volume on 3D-MDCT did not differ between the OWL (246 (IQR 50) ml) and PWL group (262 (IQR 129.5) ml), p value 0.515. Nuclear scintigraphy gastric emptying half-time was the most highly discriminant measure. A threshold of 21.2 min distinguished OWL from PWL patients with 86.4% sensitivity and 68.4% specificity. CONCLUSION: Nuclear scintigraphy is a potentially highly accurate tool in the functional assessment of sleeve gastrectomy physiology. It appears to perform better as a diagnostic test than volumetric assessment. Gastric volume did not correlate with weight loss outcomes. We have established diagnostic criteria of greater than 21 min to assess sleeve failure, which is linked to suboptimal weight loss outcomes.

Long-term Outcomes of Laparoscopic Sleeve Gastrectomy as a Revisional Procedure Following Adjustable Gastric Banding: Variations in Outcomes Based on Indication.

BACKGROUND: Significant controversy exists regarding the indications and outcomes after laparoscopic adjustable gastric banding (LAGB) conversions to laparoscopic sleeve gastrectomy (LSG). AIM: To comprehensively determine the long-term outcomes of sleeve gastrectomy as a revisional procedure after LAGB across a range of measures and determine predictors of outcomes. METHODS: Six hundred revision LSG (RLSG) and 1200 controls (primary LSG (PLSG)) were included. Patient demographics, complications, follow-up, and patient-completed questionnaires were collected. RESULTS: RLSG vs controls; females 87% vs 78.8%, age 45 ± 19.4 vs 40.6 ± 10.6 years, p = 0.561; baseline weight 119.7 ± 26.2 vs 120.6 ± 26.5 kg p = 0.961). Follow-up was 87% vs 89.3%. Weight loss in RLSG at 5 years, 22.9% vs 29.6% TBWL, p = 0.001, 10 years: 19.5% vs 27% TBWL, p = 0.001. RLSG had more complications (4.8 vs 2.0% RR 2.4, p = 0.001), re-admissions (4.3 vs 2.4% RR 1.8, p = 0.012), staple line leaks (2.5 vs 0.9%, p = 0.003). Eroded bands and baseline weight were independent predictors of complications after RLSG. Long-term re-operation rate was 7.3% for RLSG compared to 3.2% in controls. Severe oesophageal dysmotility predicted poor weight loss. RLSG reported lower quality of life scores (SF-12 physical component scores 75.9 vs 88%, p = 0.001), satisfaction (69 vs 93%, p = 0.001) and more frequent regurgitation (58% vs 42%, p = 0.034). CONCLUSION: RLSG provides long-term weight loss, although peri-operative complications are significantly elevated compared to PLSG. Longer-term re-operation rates are elevated compared to PLSG. Four variables predicted worse outcomes: eroded band, multiple prior bands, severe oesophageal dysmotility and elevated baseline weight.

Changes in Oesophageal Transit, Macro-Reflux Events, and Gastric Emptying Correlate with Improvements in Gastro-Intestinal Symptoms and Food Tolerance Early Post Sleeve Gastrectomy.

PURPOSE: There are significant alterations in gastro-intestinal function, food tolerance, and symptoms following sleeve gastrectomy (SG). These substantially change over the first year, but it is unclear what the underlying physiological basis for these changes is. We examined changes in oesophageal transit and gastric emptying and how these correlate with changes in gastro-intestinal symptoms and food tolerance. MATERIAL AND METHODS: Post-SG patients undertook protocolised nuclear scintigraphy imaging along with a clinical questionnaire at 6 weeks, 6 months, and 12 months. RESULTS: Thirteen patients were studied: mean age (44.8 ± 8.5 years), 76.9% females, pre-operative BMI (46.9 ± 6.7 kg/m2). Post-operative %TWL was 11.9 ± 5.1% (6 weeks) and 32.2 ± 10.1% (12 months), p-value < 0.0001. There was a substantial increase of meal within the proximal stomach; 22.3% (IQR 12%) (6 weeks) vs. 34.2% (IQR 19.7%) (12 months), p = 0.038. Hyper-accelerated transit into the small bowel decreased from 6 weeks 49.6% (IQR 10.8%) to 42.7% (IQR 20.5%) 12 months, p = 0.022. Gastric emptying half-time increased from 6 weeks 19 (IQR 8.5) to 12 months 27 (IQR 11.5) min, p = 0.027. The incidence of deglutitive reflux of semi-solids decreased over time; 46.2% (6 weeks) vs. 18.2% (12 months), p-value < 0.0001. Reflux score of 10.6 ± 7.6 at 6 weeks vs. 3.5 ± 4.4 at 12 months, (p = 0.049) and regurgitation score of 9.9 ± 3.3 at 6 weeks vs. 6.5 ± 1.7, p = 0.021 significantly reduced. CONCLUSIONS: These data demonstrate that there is an increase in the capacity of the proximal gastric sleeve to accommodate substrate over the first year. Gastric emptying remains rapid but reduce over time, correlating with improved food tolerance and reduced reflux symptoms. This is likely the physiological basis for the changes in symptoms and food tolerance observed early post-SG.

Delayed Gastric Emptying After Sleeve Gastrectomy Is Associated with Poor Weight Loss.

BACKGROUND: Intermediate to long-term weight regain is a major challenge following sleeve gastrectomy (SG). Physiological changes that mediate the extent of weight loss remain unclear. We aimed to determine if there were specific esophago-gastric transit and emptying alterations associated with weight regain. MATERIAL AND METHODS: Participants greater than 12 months post-SG were categorized into optimal (n = 29) and poor weight loss (PWL) (n = 72). All patients underwent a liquid contrast barium swallow demonstrating normal post-surgical anatomy and a protocolized nuclear scintigraphy designed specifically to characterize gastric emptying following SG. RESULTS: The %total weight loss in the optimal group was 26.2 ± 10.5 vs. 14.3 ± 8.8% in the PWL group (p = 0.001). Scintigraphy showed PWL had relatively increased gastric emptying half-time (GE 1/2t) 35 (IQR 23) min vs 19 (IQR 5.5) min (p = 0.001). The multivariate regressions delineated GE 1/2t as the best diagnostic measure for PWL (OR 1.16; CI 1.04-1.29, p-value 0.021). The probability of PWL increased by 16% for every 1-min increase above 21 min of GE 1/2t. A threshold of 21 min was found to have 88% sensitivity and 69% specificity predicting poor weight loss. CONCLUSION: Gastric emptying half-times greater than 21 min appear to reliably correlate with poor weight loss following SG. Additionally, further elevations above 21 min in emptying half-time increase the risk of poor weight loss. We have shown nuclear scintigraphy represents a simple and accurate diagnostic tool in patients who experience poor weight loss after SG, provided substantially altered reporting references in interpreting nuclear scintigraphy are applied.

Comprehensive Analysis of Improvements in Health-Related Quality of Life and Establishment of QALY Gains in a Government-Funded Bariatric Surgical Program with 5-Year Follow-up.

PURPOSE: Bariatric surgery is an efficacious intervention for substantial and sustained weight reduction in individuals with morbid obesity resulting in health improvements. However, the changes to a patient's health related quality of life (HRQoL) in the medium to longer term after bariatric surgery have not been adequately characterized. Our aim was to evaluate the change to patient HRQoL 5 years following bariatric surgery in an Australian government-funded hospital system and determine the significance of relationships between change in physical and mental assessment scores and HRQoL utility scores. MATERIALS AND METHODS: We performed a longitudinal panel study of 81 adult patients who underwent primary bariatric surgery at an Australian tertiary government-funded hospital and completed multi-attribute utility (MAU), multi-attribute non-utility (MA), and disease-specific adjusted quality of life (AQoL) questionnaires before and after bariatric surgery. RESULTS: At a mean (SD) 5.72 (1.07) years postbariatric surgery, participants demonstrated statistically significant improvements in mean AQoL-8D utility (0.135 (0.21); P < 0.0001), yielding a mean 3.2 (1.67) QALYs gained. Beck Depression Inventory-II scores improved (baseline mean 17.35 (9.57); 5-year mean 14.7 (11.57); P = 0.037). Short Form-36 scores improved in the domains of physical functioning and role limitations due to physical health and general health. Change in depression scores and patient satisfaction with surgery were found to be significant predictors of follow up AQoL utility scores. CONCLUSIONS: Bariatric surgery improves physical and psychological quality of life measures over 5 years. The improvement of patient QALYs provide insight to the potential cost utility of publicly funded bariatric surgery in the medium term.

Tubularized and Effaced Gastric Cardia Mimicking Barrett Esophagus Following Sleeve Gastrectomy: Protocolized Endoscopic and Histological Assessment With High-resolution Manometry Analysis.

OBJECTIVE: To describe expected endoscopic and histological changes at gastro-esophageal junction (GEJ) and define diagnostic paradigms for Barrett esophagus (BE) postsleeve gastrectomy (SG). SUMMARY BACKGROUND DATA: De novo incidence of BE post SG was reported as high as 18.8%. A confounding factor is the lack of standardized definition of BE post SG, which may differ from the general population due to procedure-induced alterations of GEJ. METHODS: Part 1 involved evaluating endoscopic changes of GEJ post SG (N = 567) compared to pre SG (N = 320), utilizing protocolized preoperative screening, postoperative surveillance and synoptic reporting. Part 2 involved dedicated studies examining causes of altered anatomical and mucosal GEJ appearance using histopathology (N = 55) and high-resolution manometry (HRM) (N = 15). RESULTS: Part 1 - A characteristic tubularized cardia segment projecting supra-diaphragmatically was identified and almost exclusive to post SG (0.6% vs.26.6%, P < 0.001). True BE prevalence was low (4.1%pre SG vs. 3.8%post SG, P = 0.756), esophagitis was comparable (32.1% vs. 25.9%, P = 0.056). Part 2 - Histologically-confirmed BE was found in 12/55 patients, but 70.8% had glandular-type gastric mucosa implying tubularized cardia herniation. HRM of tubularized cardia demonstrated concordance of supra-diaphragmatic cardia herniation between endoscopy and HRM (3 cm vs. 3.2 cm, P = 0.168), with frequent elevated isobaric intraluminal pressurizations in supra-and infra-diaphragmatic cardia compartments. CONCLUSION: A novel appearance of tubularized cardia telescoping supra-diaphragmatically with flattening of gastric folds is common post SG, likely associated with isobaric hyper-pressurization of proximal stomach. incidence of true BE post SG is low in short-intermediate term. These provided a clear framework for approaching endoscopic screening and surveillance, with correct anatomical and mucosal identifications, and clarified key issues of SG and BE.

Long-Term Outcomes of Revisional Malabsorptive Bariatric Surgery: Do the Benefits Outweigh the Risk?

PURPOSE: To evaluate the long-term outcomes of revisional malabsorptive bariatric surgery. MATERIALS AND METHODS: Malabsorptive bariatric procedures are increasingly performed in the revisional setting. We collated and analysed prospectively recorded data for all patients who underwent a revisional Biliopancreatic diversion + / - duodenal switch (BPD + / - DS) over a 17-year period. RESULTS: We identified 102 patients who underwent a revisional BPD + / - DS. Median follow-up was 7 years (range 1-17). There were 21 (20.6%) patients permanently lost to follow-up at a median of 5 years postoperatively. Mean total weight loss since the revisional procedure of 22.7% (SD 13.4), 20.1% (SD 10.5) and 17.6% (SD 5.5) was recorded at 5, 10 and 15 years respectively. At the time of revisional surgery, 23 (22.5%) patients had diabetes and 16 (15.7%) had hypercholesterolaemia with remission of these occurring in 20 (87%) and 7 (44%) patients respectively. Nutritional deficiencies occurred in 82 (80.4%) patients, with 10 (9.8%) patients having severe deficiencies requiring periods of parenteral nutrition. Seven (6.9%) patients required limb lengthening or reversal procedures. There were 16 (15.7%) patients who experienced a complication within 30 days, including 3 (2.9%) anastomotic leaks. Surgery was required in 42 (41.2%) patients for late complications. CONCLUSION: Revisional malabsorptive bariatric surgery induces significant long-term weight loss and comorbidity resolution. High rates of temporary and permanent attrition from follow-up are of major concern, given the high prevalence of nutritional deficiencies. These data question the long-term safety of malabsorptive bariatric procedures due to the inability to ensure compliance with nutritional supplementation and long-term follow-up requirements. KEY POINTS: • Revisional bariatric surgery workload is increasing • Revisional malabsorptive surgery is efficacious for weight loss and comorbidity resolution • Revisional malabsorptive surgery is associated with high rates of nutritional deficiencies • Attrition from follow-up in this specific cohort of patients is of particular concern due to the risk of undiagnosed and untreated nutritional deficiencies.

Pathophysiological Mechanisms of Gastro-esophageal Reflux After Sleeve Gastrectomy.

OBJECTIVE: To evaluate the mechanisms associated with reflux events after sleeve gastrectomy (SG). SUMMARY BACKGROUND DATA: Gastro-esophageal reflux (GERD) post-SG is a critical issue due to symptom severity, impact on quality of life, requirement for reoperation, and potential for Barrett esophagus. The pathophysiology is incompletely delineated. METHODS: Post-SG patients, stratified into asymptomatic and symptomatic, underwent protocolized nuclear scintigraphy (n = 83), 24-hour esophageal pH monitoring, and stationary manometry (n = 143) to characterize reflux patterns. Ten patients underwent fasting and postprandial concurrent manometry and pH for detailed analysis of reflux events. RESULTS: Baseline demographics between cohorts were similar: Age 47.2 ± 11.6 versus 44.1 ± 11.3 years ( P = 0.121); females 73.2% versus 90.8% ( P = 0.005); excess weight loss 53.8 ± 28.1% versus 57.4 ± 25.5% ( P = 0.422), follow-up duration 12.3 versus 7.4 months ( P = 0.503). Nuclear scintigraphy delineated bolus-induced deglutitive reflux events (29.6% vs 62.5%, P = 0.005) and postprandial reflux events [4 (IQR2) versus 4 (IQR 3) events, P = 0.356]. Total acid exposure was significantly elevated in the symptomatic population (7.7% vs 3.6%, P < 0.001), especially fasting acid exposure (6.0% vs 1.3%, P < 0.001). pH/manometry analysis demonstrated acute elevations of the gastro-esophageal pressure gradient (>10 mm Hg) underpinned most reflux events. Swallow-induced intragastric hyper-pressur-ization was associated with individual reflux events in most patients (90% in fasting state and 40% postprandial). CONCLUSIONS: We found reflux to be strongly associated with SG and identified 3 unique categories. Bolus-induced deglutitive and postprandial reflux occurred in most patients. Elevated fasting esophageal acid exposure mediated symptoms. Frequent, significant elevation in the gastro-esophageal pressure gradient was the mechanism of reflux and seemed to relate to the noncompliant proximal stomach.

Expected Values of Esophageal Transit and Gastric Emptying Scintigraphy Post-uncomplicated Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) results in significant anatomical and physiological alterations of the esophagus and stomach, including food tolerance. Currently, there is no consensus on the parameters of abnormal esophageal transit and gastric emptying in this population. We describe standardized esophageal transit and gastric emptying protocols, and define expected values following an uncomplicated SG. MATERIALS AND METHODS: In 43 asymptomatic post-SG patients with optimal weight loss, a standardized liquid and semi-solid (oatmeal) esophageal transit study, plus a 90-min semi-solid gastric emptying study with dynamic 5-s image acquisition to assess gastroesophageal reflux, was performed. Gastric emptying half-time and retention rate was calculated. Esophageal transit and reflux were graded by visual inspection of images. RESULTS: Thirty-one female and 12 male patients participated: mean age 49.0±10.7 years, pre-operative BMI 47.6±7.0 kg/m2, excess weight loss 58.8±26.0% at median follow-up of 7.4 months. The standardized semi-solid meal and liquid preparations were well tolerated. Delays in esophageal transit of liquid and semi-solid boluses were infrequent (7.0% and 16.3% respectively). Deglutitive reflux of both semi-solids and liquids was common (48.8% and 32.6%). The median semi-solid gastric emptying half-time was 21.0 min. A large proportion of substrate transited into the small bowel on initial image acquisition (median 39.1%). Reflux events during gastric emptying were common (median 5.0 events, 12.7% of image acquisition time). CONCLUSIONS: Rapid gastric emptying with asymptomatic deglutitive and post-prandial gastroesophageal reflux events are common following SG. We have defined the expected values of standardized esophageal transit and gastric emptying scintigraphy specifically tailored to SG patients.

Diagnostic Criteria for Gastro-esophageal Reflux Following Sleeve Gastrectomy.

BACKGROUND: Gastro-esophageal reflux disease (GERD) post-sleeve gastrectomy (SG) is a controversial issue and diagnostic dilemma. Strong heterogeneity exists in the assessment of reflux post-SG, and better diagnostic tools are needed to characterize symptomatic reflux. We aimed to determine the discriminant factors of symptomatic reflux and establish diagnostic thresholds for GERD following SG. MATERIALS AND METHODS: Patients post-SG were categorized into asymptomatic and symptomatic cohorts and completed validated symptom questionnaires. All patients underwent stationary esophageal manometry and 24-h ambulatory pH monitoring. Univariate and multivariate analyses were conducted to determine the strongest discriminant factors for GERD. RESULTS: Baseline characteristics of the asymptomatic cohort (n = 48) and symptomatic cohort (n = 76) were comparable. The median post-operative duration was 7.3 (14.1) vs 7.5 (10.7) months (p = 0.825). The symptomatic cohort was more female predominant (90.8 vs 72.9%, p = 0.008). Reflux scores were significantly higher in the symptomatic group (36.0 vs 10.5, p = 0.003). Stationary manometry parameters were similar, including hiatus hernia prevalence and impaired esophageal motility. The symptomatic cohort had significantly higher total acid exposure, especially while supine (11.3% vs 0.6%, p < 0.001). Univariate and multivariate regressions delineated reflux score and supine acid exposure as discriminant factors for symptomatic reflux. The thresholds for distinguishing symptomatic reflux are as follows: reflux score of 11.5 (sensitivity 84.0%, specificity 68.2%) and supine acid exposure of 2.65% (sensitivity 67.1%, specificity 70.8%). CONCLUSION: A reflux score of 11.5 or more or supine acid exposure of 2.65% or more should be considered diagnostic in defining symptomatic reflux following SG.

Mechanisms of Esophageal and Gastric Transit Following Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) patients have substantially altered anatomy. The mechanism of rapid gastric emptying and the role of esophageal contractile function in esophago-gastric transit has not been defined. We aimed to determine the mechanisms of esophago-gastric transit and role of esophageal function following sleeve gastrectomy. METHODS: Prospective study of twenty-six asymptomatic participants post SG underwent nuclear scintigraphy and high-resolution manometry. Fourteen had semi-solid stress barium to model the emptying process. Concurrent video fluoroscopy and manometry were performed on 7 participants. RESULTS: Demographic data are as follows: age 45.3 ± 15.0 years, 73.1% female, excess weight loss 62.2 ± 28.1% at 8 months. Scintigraphy showed rapid gastric emptying (24.4 ± 11.4 vs. 75.80 ± 45.19 min in control, p < 0.001) with 35.24 ± 17.12% of bolus transited into small bowel on initial frame. Triggered deglutitive reflux was common (54.4% vs. 18.2%, p = 0.017). Stress barium delineated separate vertical and antral gastric compartments with cyclical emptying of 8 stages, including reflux-induced repeated esophageal peristalsis. During manometry, ramping effects were noted, with sequential swallows producing sustained isobaric pressurizations in proximal stomach (33.6 ± 29.5 mmHg). Video fluoroscopy showed individual esophageal peristalsis generating pressurizations at 5.0 ± 1.4 cm below lower esophageal sphincter (LES), at amplitude of 31.6 ± 13.1 mmHg, associated with intragastric transit. Pressurizations were sustained for 17.3 ± 8.2 s, similar to the prolonged LES contraction (18.5 ± 9.0 s, p = 0.355). CONCLUSIONS: Repeated esophageal peristaltic contractions induced isobaric pressurization of proximal stomach, thus providing the drive to pressurize and empty the vertical compartment of the gastric sleeve. Transit following SG appeared to be esophageal-mediated and followed a distinct cycle with strong associations with reflux.

Long-Term Matched Comparison of Adjustable Gastric Banding Versus Sleeve Gastrectomy: Weight Loss, Quality of Life, Hospital Resource Use and Patient-Reported Outcome Measures.

BACKGROUND: Comparisons of bariatric procedures across a range of outcomes are required to better inform selection of procedures and optimally allocate health care resources. AIMS: To determine differences in outcomes between laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) across nine outcome domains. METHODS: Matched primary LSG or LAGB across age, weight and surgery date were recruited. Data were collected from a prospective database and patient-completed questionnaires. RESULTS: Patients (n = 520) were well-matched (LAGB vs. LSG; age 41.8 ± 11.2 vs. 42.7 ± 11.7 years, p = 0.37; male 32.4% vs. 30.2%, p = 0.57; baseline weight 131.2 ± 30.5 vs. 131.0 ± 31.1 kg, p = 0.94). Follow-up rate was 95% at a mean of 4.8 years. LAGB attended more follow-up visits (21 vs. 13, p < 0.05). Mean total body weight loss was 27.7 ± 11.7% vs. 19.4 ± 11.1% (LSG vs. LAGB, p < 0.001). LAGB had more complications (23.8% vs. 10.8%, p < 0.001), re-operations (89 vs. 13, p < 0.001) and readmissions (87 vs. 32, p < 0.001). However, early post-operative complications were higher post-LSG (2.6 vs. 9.2%, p = 0.007). Length of stay (LOS) was higher post-LSG compared with LAGB (5.2 ± 10.9 vs. 1.5 ± 2.2 days, p < 0.001). LSG patients reported better quality of life (SF-36 physical component score 54.7 ± 7.9 vs. 47.7 ± 10.8, p = 0.002) and satisfaction (9.2 ± 1.9 vs. 8.4 ± 1.6, p = 0.001) and less frequent regurgitation (1.2 ± 1.2 vs. 0.7 ± - 1.1, p = 0.032) and dysphagia (2.0 ± 1.3 vs. 1.3 ± 1.6, p = 0.007). CONCLUSION: This study showed high long-term follow-up rates in a large cohort of well-matched patients. Weight loss was greater with LSG. LAGB reported more re-operations and less satisfaction with the outcome. LOS was driven by patients with complications. This study has reinforced the need for comprehensive measurement of outcomes in bariatric surgery.

Correction to: Improving Compliance with Very Low Energy Diets (VLEDs) Prior to Bariatric Surgery-A Randomized Controlled Trial of Two Formulations.

In the original article the name of author Alexandra Klejn was misspelled.

Improving Compliance with Very Low Energy Diets (VLEDs) Prior to Bariatric Surgery-a Randomised Controlled Trial of Two Formulations.

INTRODUCTION: Preoperative very low energy diets (VLEDs) improve access during bariatric surgery. Compliance with traditional VLED is variable, mainly due to gastrointestinal side effects. Formulite™ is a new formulation of VLED, with higher protein, soluble fibre and probiotics. AIMS: To compare traditional VLED (Optifast™) with the new VLED (Formulite™) and assess compliance, weight loss, satisfaction, side effects and surgical access. METHODS: This was a randomised double-blinded study involving patients scheduled for bariatric surgery. The primary outcome was compliance, assessed by urinary ketone concentration and proportion of patients in ketosis at 2 weeks. Secondary outcomes were weight loss, satisfaction and patient reported outcomes, gastrointestinal side effects and operative conditions. RESULTS: There were 69 participants: 35 in the Formulite™ group and 34 in the Optifast™ group. Ketosis at 2 weeks was achieved in both groups (88.5% vs 83.3%, Formulite™ vs. Optifast™, p = 0.602). Urinary ketones were higher with Formulite™ (1.5 vs 15 mmol/L, p = 0.030). Total body weight loss percentage, hunger and operative conditions were similar in both groups. Formulite™ produced less flatulence (score 3 vs 2, p = 0.010) and emotional eating (score 2 vs 1, p = 0.037); however, Optifast™ ranked higher in terms of taste (score 4 vs 3, p = 0.001) and overall satisfaction (score 5 vs 7, p = 0.011). CONCLUSIONS: Compliance over 2 weeks was high in both VLEDs with most subjects achieving ketosis. Overall satisfaction was moderately high, although variable. Whilst Formulite™ is a viable alternative to Optifast™, better formulations of VLED that addresses key adverse effects, whilst achieving ketosis, would be of significant value.

Effect of Body Mass Index, Metabolic Health and Adipose Tissue Inflammation on the Severity of Non-alcoholic Fatty Liver Disease in Bariatric Surgical Patients: a Prospective Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), driven by the obesity epidemic, has become the most common form of liver disease. Despite this, there is controversy regarding the prevalence and severity of NAFLD in obesity. Obesity-related factors, such as increasing adiposity, metabolic disease and inflammation, may influence prevalence. We therefore prospectively measured NAFLD prevalence in obesity and studied factors associated with NAFLD. MATERIALS AND METHODS: We recruited consecutive bariatric patients. Intraoperative liver biopsies were taken. The liver, adipose tissue and serum were collected to measure inflammation. Adipocyte cell size was measured. NAFLD severity was correlated to body mass index (BMI), metabolic health and adipose characteristics. RESULTS: There were 216 participants; BMI 45.9 ± 8.9 kg/m2, age 44.4 ± 12.1 years, 75.5% female. Overall NAFLD prevalence was 74.1%, with 17.1% having non-alcoholic steatohepatitis (NASH) and/or steatofibrosis. Odds of NASH/steatofibrosis increased independently with BMI category (odds ratio (OR) 2.28-3.46, all p < 0.05) and metabolic disease (OR 3.79, p = 0.003). These odds markedly increased when both super obesity (BMI > 50) and metabolic disease were present (OR 9.71, p < 0.001). NASH/steatofibrosis prevalence was significantly greater with diabetes, hypertension and dyslipidemia. Although greater visceral adipocyte hypertrophy was evident in NASH/steatofibrosis, there was no significant association between adipose inflammation and NASH/steatofibrosis. CONCLUSION: NAFLD remains endemic in obesity; however, NASH/steatofibrosis are less common than previously reported. Worsening obesity and metabolic disease increase odds of NAFLD independently, with substantially compounded effect with both. These observations may help with risk stratification in obese populations. We were unable to delineate clear associations between adipose inflammation and NASH/steatofibrosis in this obese population. TRIAL REGISTRATION: Australian Clinical Trials Registry ( ACTRN12615000875505 ).

Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty liver disease in severe and morbid obesity.

INTRODUCTION: In obese individuals, nonalcoholic fatty liver disease (NAFLD) is common but often goes undiagnosed, and therefore untreated. The presence of significant fibrosis is a key determinant of NAFLD progression, and liver steatosis has substantial cardiovascular implications. We aimed to determine the diagnostic accuracy of common noninvasive diagnostic tests for steatosis and fibrosis in the obese. METHODS: We recruited 182 severely and morbidly obese individuals undergoing bariatric surgery (age 44 ± 12 years, body mass index 45.1 ± 8.3 kg/m2). Medical history, blood tests and liver biopsy were taken on the day of surgery. Serum steatosis and fibrosis scores were calculated. In a subgroup of patients, transient elastography with controlled attenuation parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy (1H-MRS) (n = 49) were performed. RESULTS: 1H-MRS had excellent diagnostic accuracy for steatosis, with strong correlation to steatosis (r = 0.647, p < 0.001), good AUROC (0.852, p = 0.001), sensitivity (81.3%) and specificity (87.5%). However, due to low feasibility in this cohort (65.3% success), this was substantially decreased with intention-to-diagnose analysis (sensitivity 50.0%, specificity 60.9%). CAP had good feasibility (80.5%), and performed better in intention-to-diagnose analysis (AUROC 0.688, sensitivity 84.8%, specificity 47.2%). Serum steatosis scores performed poorly, with comparable accuracy to ALT. For significant fibrosis, TE had the best accuracy (AUROC 0.903, p = 0.007), which remained reasonable after intention-to-diagnose analysis (sensitivity 100%, specificity 59.0%). A combination approach using CAP with ALT for steatosis and TE with Forn index for fibrosis yielded reasonable overall accuracy. CONCLUSIONS: 1H-MRS and TE/CAP had greatest accuracy for NAFLD-related steatosis and fibrosis. Failure rates in obesity significantly diminished diagnostic ability. Use of a combination of serum and imaging tests improved overall feasibility of assessment and diagnostic accuracy in obese individuals.

Visual Liver Score to Stratify Non-Alcoholic Steatohepatitis Risk and Determine Selective Intraoperative Liver Biopsy in Obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are endemic in obesity. We aimed to evaluate the diagnostic accuracy and reproducibility of a simple intraoperative visual liver score to stratify the risk of NASH and NAFLD in obesity and determine the need for liver biopsy. METHODS: This is a prospective cohort study of obese adults undergoing bariatric surgery. The surgical team used a visual liver score to evaluate liver colour, size and surface. This was compared to histology from an intraoperative liver biopsy. RESULTS: There were 152 participants, age 44.6 ± 12 years, BMI 45 ± 8.3 kg/m2. Prevalence of NAFLD was 70.4%, with 12.1% NASH and 26.4% borderline NASH. Single-visual components were less accurate than total composite score. Steatosis was most accurately identified (significant steatosis: AUROC 0.746, p < 0.05; severe steatosis: AUROC 0.855, p < 0.05). NASH was identified with moderate accuracy (AUROC 0.746, p = 0.001), with sensitivity 75% for a score ≥ 2. Stratification into low (≤ 1) and high-risk (≥ 4) scores accurately identified patients who should or should not have an intraoperative biopsy. Most patients with a normal-appearing liver did not have disease (94.4%). The structured visual assessment was quick and interobserver agreement was reasonable (κ = 0.53, p < 0.05). CONCLUSIONS: A simple, structured tool based on liver appearance can be a useful and reliable tool for NAFLD risk stratification and identification of patients who would most and least benefit from a biopsy. A normal liver appearance reliably excludes significant liver disease, avoiding the need for liver biopsy in patients otherwise at high clinical risk of NASH.

Detailed Description of Change in Serum Cholesterol Profile with Incremental Weight Loss After Restrictive Bariatric Surgery.

INTRODUCTION: Dyslipidemia affects up to 75% of morbidly obese individuals and is a key driver of cardiovascular disease. Weight loss is an established strategy to improve metabolic risk, including dyslipidemia. We aimed to determine weight loss goals for resolution of serum lipid abnormalities, by measuring improvements during progressive weight loss in obese individuals. METHODS: We performed a prospective cohort study of obese individuals with the metabolic syndrome undergoing adjustable gastric banding. Lipid levels were monitored monthly for 9 months, then three monthly until 24 months. RESULTS: There were 101 participants included, age 47.4 ± 10.9 years with body mass index 42.6 ± 5.9 kg/m2. At 24 months, total body weight loss (TBWL) was 18.3 ± 7.9%. This was associated with significant improvements in high-density lipoprotein (HDL) (1.18 vs 1.47, p < 0.001), triglyceride (2.0 vs 1.4, p < 0.001), and total cholesterol to HDL ratio (TC:HDL) (4.6 vs 3.6, p < 0.001). Over this time, progressive and linear improvements in HDL, triglycerides, and TC:HDL were seen with incremental weight loss (observed at 2.5% TBWL intervals). Significant improvements occurred after a threshold weight loss of 7.5-12.5% TBWL was achieved, with odds ratio (OR) 1.48-2.50 for normalization. These odds improved significantly with increasing weight loss (OR 18.2-30.4 with > 25% TBWL). Despite significant weight loss, there was no significant change in low-density lipoprotein (LDL). CONCLUSION: Significant improvements in triglycerides, HDL, and TC:HDL occur after 7.5-12.5% TBWL, with ongoing benefit after greater weight loss. LDL needs to be addressed independently, as this was not observed to respond to weight loss alone. TRIAL REGISTRATION NUMBER: Australian Clinical Trials Registry (ACTRN12610000049077).

Radical gastric cancer surgery results in widespread upregulation of pro-tumourigenic intraperitoneal cytokines.

BACKGROUND: Radical surgical resection is the mainstay of curative treatment for oesophagogastric malignancy. However, survival and recurrence rates remain poor. Theoretical data suggests that the inflammatory response to surgery can promote tumour recurrence. The local and systemic inflammatory response to radical oesophagogastric cancer surgery has not been fully characterized. We aimed to measure this response, particularly factors associated with tumour implantation. METHODS: Consecutive patients undergoing radical junctional or gastric cancer resection over 12 months were recruited. Repeated serum and adipose tissue were collected intra-operatively. Adipose tissue was collected adjacent and remote to the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post-operatively, daily serum was collected for 7 days, and analysed for inflammatory cell profile and cytokine concentration. RESULTS: There were nine patients recruited (67.1 ± 2.1 years). mRNA expression of interleukin-6 (IL-6), CC-chemokine ligand-2 and IL-1ß increased in adipose tissue intra-operatively (P < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6 concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P < 0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum tumour necrosis factor-α was elevated throughout, and IL-1ß levels were unaffected. Leukocyte and neutrophil populations increased, while T-cell and dendritic cell populations decreased intra-operatively (P < 0.05). CONCLUSION: Radical surgery dramatically upregulates the expression of pro-tumourigenic cytokines in the peritoneum. There is also a marked systemic immune and inflammatory response to surgery, including downregulation of T-cell and dendritic cell populations. This offers two potential pathways that may facilitate tumour progression - local inflammation promoting peritoneal adherence and implantation, and secondary suppression of immunosurveillance due to circulating inflammatory response.

Diabetes Outcomes More than a Decade Following Sustained Weight Loss After Laparoscopic Adjustable Gastric Band Surgery.

BACKGROUND: Long-term outcome data are needed to define the role of bariatric surgery in type 2 diabetes (T2D). To address this, we collated diabetes outcomes more than a decade after laparoscopic adjustable gastric band (LAGB) surgery. METHOD: Clinical and biochemical measures from 113 obese T2D patients who underwent LAGB surgery in 2003 and 2004 were analyzed. Diabetes remission was defined as HbA1c < 6.2% (44 mmol/mol) and fasting glucose < 7.0 mmol/L. RESULTS: Seventy-nine patients had weight data at 10 years and attained a median [Q1, Q3] weight loss of 16 [10, 21] percent. Sixty patients attended a follow-up assessment. Their baseline HbA1c of 7.8 [7.1, 9.3] percentage units (62 [54, 78] mmol/mol) had decreased to 6.6 [6.1, 8.4] (49 [43, 68] mmol/mol) despite no significant change in glucose-lowering therapy. Eleven patients (18%) were in diabetes remission and another 18 had HbA1c ≤ 6.5%. Significant improvements in physical measures of quality of life, blood pressure, and lipid profile were also observed but there was no change in the proportion of patients with albuminuria and a significant decline in estimated glomerular filtration rate. Twelve patients in the follow-up cohort (20%) required anti-reflux medication after surgery and 26 (43%) underwent gastric band revision surgery. CONCLUSION: Weight loss for over 10 years after LAGB surgery delivers clinically meaningful improvements in HbA1c, blood pressure, lipids, and quality of life at the cost of a high rate of revision surgery and increased use of anti-reflux medication. These findings support the use of bariatric surgery as a long-term treatment for weight loss and wellbeing in patients with T2D. STUDY REGISTRATION: Registered with the Australian Clinical trials registry as ACTRN12615000089538.