The lncRNA Malat1 inhibits miR-15/16 to enhance cytotoxic T cell activation and memory cell formation.

Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, intracellular bacteria, and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and memory. Comparative Argonaute-2 high-throughput sequencing of crosslinking immunoprecipitation (AHC) combined with gene expression profiling in normal and miR-15/16-deficient mouse T cells revealed a large network of hundreds of direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak. This binding site was among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16-binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of interleukin 2 (IL-2) and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence in mice following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of long non-coding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.

Bariatric surgery, novel glucose-lowering agents, and insulin for type 2 diabetes and obesity: Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity. METHODS: Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight. RESULTS: A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months. CONCLUSION: Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity. PROSPERO REGISTRATION NO: CRD42020201507.

The lncRNA Malat1 Inhibits miR-15/16 to Enhance Cytotoxic T Cell Activation and Memory Cell Formation.

Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, many intracellular bacteria and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 also play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and T cell memory. Comparative Argonaute-2 high throughput sequencing of crosslinking immunoprecipitation (Ago2 HITS-CLIP, or AHC) combined with gene expression profiling in normal and miR-15/16-deficient T cells revealed a large network of several hundred direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, the long non-coding RNA Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak in T cells. This binding site was also among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16 binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of IL-2 and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of long noncoding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.

Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver.

Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8+ T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

The comparative effects of metabolic surgery, SGLT2i, or GLP-1RA in patients with obesity and type 2 diabetes: a retrospective cohort study.

BACKGROUND: New antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes. OBJECTIVES: To compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months. SETTING: Hong Kong Hospital Authority database from 2006-2017. METHODS: This is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups. RESULTS: Patients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (-5.39, -.56, -.40 kg/m2, P < .001), % total weight loss (15.16%, 1.34%, 1.63%, P < .001), systolic (-2.21, -.59, 1.28 mm Hg, P < .001) and diastolic (-1.16, .50, -.13 mm Hg, P < .001) blood pressure, HbA1c (-1.80%, -.77%, -.80%, P < .001), triglycerides (-.64, -.11, -.09 mmol/L, P < .001), and estimated glomerular filtration rate (3.08, -1.37, -.41 mL/min/1.73m2, P < .001) after 12 months compared with patients with SGLT2i and GLP1-RA. Although the metabolic surgery group incurred the greatest direct medical costs (US$33,551, US$10,945, US$10,627, P < .001), largely due to the surgery itself and related hospitalization, the total monthly direct medical expenditure of metabolic surgery group became lower than that of SGLT2i and GLP-1RA groups at 7 months. CONCLUSION: Beneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.

Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.

OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM). DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24. RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05). CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness. TRIAL REGISTRATION NUMBER: NCT03127696.

Alterations in the Gut Virome in Obesity and Type 2 Diabetes Mellitus.

BACKGROUND & AIMS: Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM. METHODS: There were 128 obese subjects (body mass index ≥28 kg/m2) and 101 lean controls (body mass index ≥18.5 and <23 kg/m2) recruited from 2 regions in China (Hong Kong and Kunming). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome, and viral-bacterial correlations were compared between obese subjects and lean controls. RESULTS: Obese subjects, especially those with T2DM (ObT2), had a decreased gut viral richness and diversity compared with lean controls in the Hong Kong cohort (P < .05), while no significant differences were observed in the Kunming cohort. Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, 17 differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecologic analysis revealed that intensive transkingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (P < .001). CONCLUSIONS: Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Obesity accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that the gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.

Accuracy of High-Resolution Manometry in Hiatal Hernia Diagnosis in Primary and Revision Bariatric Surgery.

PURPOSE: There is a complex association between obesity, hiatal hernia (HH), and reflux. There is a deficiency of literature on the accuracy of preoperative high-resolution manometry (HRM) in detecting HH before both primary and revision bariatric surgery. MATERIALS AND METHODS: A retrospective analysis of a prospective database of all HRM performed before bariatric surgery from 2014 to 2019. An electronic medical records review was conducted. Sensitivity, specificity, and global diagnostic test accuracy were calculated. RESULTS: Sixty-seven patients with HRM (mean age of 44.0 ± 11.3 years, body mass index 40.8 ± 6.9 kg/m2) were eligible. Intraoperative diagnosis of HH was made in 37 patients (55.2% prevalence). The HRM sensitivity was 48.7% (95% confidence interval (CI) 31.9-65.6%), specificity 90.0% (95% CI 73.5-97.9%), and accuracy was 67.2% (95% CI 54.6-78.2%). Comparing primary (28) and revision (39) surgery, the sensitivity (37.5% vs 57.1%), specificity (75.0% vs 100%), and diagnostic accuracy (54.3% vs 76.3%) were comparable, with overlapping 95% CI. Endoscopy performed in 30 patients had a sensitivity of 25.5% (95% CI 6.8-49.9%), specificity of 100% (95% CI 75.3-100%), and accuracy of 57.8% (95% CI 38.5-75.5%) and was comparable to HRM. CONCLUSION: High-resolution manometry for the detection of HH before bariatric surgery has a high specificity and maintains a high accuracy in both primary and revision bariatric surgery.

Association between bariatric surgery and risks of cancer among Chinese patients with type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: To examine risks of cancers, obesity-related cancers (eg, cancers in digestive organs, breast, ovary, kidney, thyroid, and myeloma), cancer-related mortality, and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and obesity who underwent bariatric surgery. METHODS: A retrospective cohort of 1944 T2DM patients with obesity (345 bariatric surgery patients and 1599 matched controls) who were free of cancer from 2006 to 2017 was assembled. One-to-five propensity score matching followed by propensity score trimming was used to balance baseline covariates. RESULTS: During a mean follow-up period of 37 months, there are risks that in 3.2%, 1.4%, 0.9%, and 3.2% of bariatric patients cancer, obesity-related cancer, cancer-related mortality, and all-cause mortality, respectively, would occur. Surgical patients were found to have reduced incidence rates (IRs) of obesity-related cancer (0.531/100 person-years, 95% confidence interval [CI]: 0.172-1.238/100 person-years) and cancer of breast and genital organs (0.394/100 person-years, 95% CI: 0.048-1.424/100 person-years) than matched control patients whose IRs for obesity-related cancer and cancer of breast and genital organs were 0.627/100 person-years (95% CI: 0.426-0.889/100 person-years) and 0.521/100 person-years (95% CI: 0.277-0.891/100 person-years), respectively. Patients in the surgical group had a significant reduction in risk of all-cause mortality (hazard ratio [HR] = 0.508, P = .041). Effects of bariatric surgery on any cancers (HR = 1.254, P = .510), obesity-related cancers (HR = 0.843, P = .724), and cancer mortality (HR = 1.304, P = .694) were not significant. CONCLUSIONS: Bariatric surgery was not associated with risks of overall cancer, obesity-related cancer, and cancer mortality among T2DM patients with obesity at 3 years.

Outcomes with Intra-gastric Balloon Therapy in BMI < 35 Non-morbid Obesity: 10-Year Follow-Up Study of an RCT.

PURPOSE: Intra-gastric balloon (IGB) therapy is the most established endoscopic treatment of obesity, but there is a paucity of literature on long-term efficacy. This study aims to evaluate the short- and long-term weight loss efficacy of IGB. MATERIALS AND METHODS: Double-blinded RCT with 6-month IGB vs with sham endoscopy, in body mass index (BMI) 27-35 patients. Anthropometric, fasting glucose, and lipid profile measurement as early outcomes (up to 2 years) and 10-year follow-up. Primary outcomes were total body weight loss (kg) and BMI. Secondary outcomes were new-onset diabetes mellitus, other new comorbidities, and willingness for further intervention. RESULTS: Initial RCT recruited 99 patients (50 IGB vs 49 sibutramine group). Forty-nine patients (26 IGB vs 23 control group) participated in a 10-year review (follow-up rate of 51.6%). Total body weight loss at 6 (9.75 vs 7.48 kg, p = 0.03), 12 (6.52 vs 4.42 kg, p = 0.05), 18 (5.42 vs 3.57, p = 0.32), and 24 months (4.07 vs 2.93 kg, p = 0.56) favored the IGB group. Total weight loss (TWL) at 10 years (0.03 vs - 2.32 kg, p = 0.05) and %TWL (- 0.16 ± 12.8% vs - 2.84 ± 5.6%, p = 0.39) were not significantly different between groups. Follow-up BMI (30.97 ± 1.6 vs 30.38 ± 1.8 kg/m2, p = 1.00) was similar. At 10 years, new-onset diabetes mellitus, sleep apnoea, metabolic syndrome, and arthralgia were not significant (p > 0.05). Twenty-three (81%) IGB group vs 13 (56%) control expressed a willingness for further intervention (p < 0.01). CONCLUSION: IGB delivers weight loss to 2 years and is superior to control. However, new comorbidity development is not significantly different at 10 years. Patient that received IGB therapy were subsequently more willing for further bariatric metabolic intervention.

Effects of bariatric surgery on kidney diseases, cardiovascular diseases, mortality and severe hypoglycaemia among patients with Type 2 diabetes mellitus.

BACKGROUND: Bariatric surgery has been widely indicated for the management of obesity and related comorbidities. However, there are uncertainties pertaining to the risks of post-bariatric severe hypoglycaemia (SH), cardiovascular diseases (CVDs), end-stage kidney diseases (ESKDs) and all-cause mortality in obese patients with Type 2 diabetes mellitus (T2DM), especially among Asian populations. METHODS: A retrospective population-based cohort of 1702 obese T2DM patients who were free of CVD and ESKD were assembled based on the 2006-17 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IRs) of SH, CVD, Stage 4/5 chronic kidney diseases (CKD), ESKD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for SH, CVD and Stage 4/5 CKD events were assessed using Cox-proportional hazard models. Changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) were measured up to 60 months. RESULTS: Over a mean follow-up period of 32 months with 5725 person-years, cumulative incidences of mortality, CVD, Stage 4/5 CKD, ESKD and SH were 0, 0.036, 0.050, 0.017 and 0.020, respectively. The surgery group had a significant reduction in risk of CVD events (HR = 0.464, P = 0.015) and no occurrence of mortality events. However, there were no significant differences in risks of SH [HR = 0.469, 95% confidence interval (CI): 0.204-1.081], Stage 4/5 CKD (HR =0.896, 95% CI: 0.519-1.545) and ESKD (HR = 0.666, 95% CI: 0.264-1.683) between two groups, although IRs were lower in the surgery group. Surgical patients had significantly higher eGFR within 12 months and had significantly lower UACR until 48 months. CONCLUSIONS: Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes.

Accuracy of hiatal hernia diagnosis in bariatric patients: Preoperative endoscopy versus intraoperative reference.

BACKGROUND AND AIM: Obesity is becoming increasingly prevalent in Asia. Bariatric surgery in the region is growing in popularity to reflect increasing demand. Hiatal hernia (HH) is common among the obese population. There is a lack of evidence comparing preoperative endoscopy against intraoperative findings as a standard of reference for HH diagnosis. METHODS: This was a retrospective analysis of a bariatric procedure database from a single tertiary teaching hospital and high-volume endoscopy center. Electronic medical records were reviewed. Endoscopy results were compared to intraoperative findings, and subgroup analysis of >2 cm hernias was performed. Sensitivity, specificity, predictive values, likelihood ratios, and global diagnostic test accuracy were calculated. RESULTS: A total of 434 patients were eligible for this study, of which HH was detected in 37 patients (prevalence rate 8.55%). Mean age was 41.51 ± 11.07 years, and body mass index was 39.37 ± 5.67 kg/m2. Endoscopy sensitivity was 75.68% (95% confidence interval, 58.80-88.23%) and specificity 91.44% (88.24-94.00%). Positive likelihood ratio was 8.53 (6.11-12.79) and negative likelihood ratio 0.27 (0.15-0.47). Positive predictive value was 45.16% (36.27-54.38%) and negative predictive value 97.58% (95.80-98.62%). Accuracy of endoscopy for preoperative HH diagnosis was 90.09% (86.89-92.74%). CONCLUSION: Endoscopy can have a high diagnostic accuracy of preoperative HH diagnosis in obese Asian patients using intraoperative diagnosis as the reference standard.

Observed changes in brown, white, hepatic and pancreatic fat after bariatric surgery: Evaluation with MRI.

OBJECTIVES: To study the change in brown and white adipose tissue (BAT and WAT), as well as fat content in the liver and pancreas, in patients with morbid obesity before and after bariatric surgery. METHODS: Twelve patients with morbid obesity (F=8, M=4, age: 45.4 years (38.4-51.2), BMI: 35.2 kg/m2 (32.5-38.6)) underwent pre-op MRI at baseline and two post-op scans at 6-month and 12-month intervals after bariatric surgery. Co-registered water, fat, fat-fraction and T2* image series were acquired. Supraclavicular BAT and abdominal WAT were measured using in-house algorithms. Intrahepatic triglyceride (IHTG) was measured using MR spectroscopy and pancreatic fat was measured using a region-of-interest approach. Fat contents were compared between baseline and the first and second 6-month intervals using non-parametric analysis of Friedman's test and Wilcoxon's signed-rank test. Level of significance was selected at p=0.017 (0.05/3). Threshold of non-alcoholic fatty liver disease was set at 5.56%. RESULTS: Results indicated that BMI (p=0.005), IHTG (p=0.005), and subcutaneous (p=0.005) and visceral adipose tissues (p=0.005) were significantly reduced 6 months after surgery. Pancreatic fat (p=0.009) was significantly reduced at 12 months. Most reduction became stable between the 6-month and 12-month interval. No significant difference was observed in BAT volume, fat-fraction and T2* values. CONCLUSION: The results of this study suggest that bariatric surgery effectively reduced weight, mainly as a result of the reduction of abdominal WAT. Liver and pancreatic fat were deceased below the threshold possibly due to the reduction of free fatty acid. BAT volume, fat-fraction and T2* showed no significant changes, probably because surgery itself might not have altered the metabolic profile of the patients. KEY POINTS: • No significant changes were observed in fat-fraction, T2* and volume of brown adipose tissue after bariatric surgery. • Non-alcoholic fatty liver disease was resolved after surgery. • Abdominal white fat and liver fat were significantly reduced 6 months after surgery and become stable between 6 and 12 months while pancreatic fat was significantly reduced between 0 and 12 months.

Validation of water-fat MRI and proton MRS in assessment of hepatic fat and the heterogeneous distribution of hepatic fat and iron in subjects with non-alcoholic fatty liver disease.

BACKGROUND: Research studies demonstrated pathologic lesions were unevenly distributed in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. As hepatic steatosis occurs prior to steatohepatitis and other late stage liver conditions, the distribution pattern of hepatic fat and iron concentration should be investigated to prevent sampling variability. The first purpose of this study was to perform comparison and validation of in-house hepatic fat measurements using water-fat MRI and MRS. The second objective was to quantify hepatic fat-fraction and T2* values in left and right liver lobes using water-fat MRI. METHOD: Fifty-four non-alcoholic adults (27 NAFLD, age: 42.8 ± 11.8), 27 non-NAFLD, age: 45.5 ± 11.2) and 46 non-alcoholic teenagers (23 NAFLD (age: 15.4 ± 2.6), 23 non-NAFLD (age: 13.9 ± 2.3) were recruited. All participants underwent chemical shift water-fat MRI and 1H MRS at 3 T. Hepatic steatosis was defined by intrahepatic triglyceride more than the threshold of 5.56% using MRS (clinical reference) and non-alcoholic was defined by alcohol ingestion of no more than 30 g and 20 g per day for male and female respectively. Hepatic fat-fractions in left and right liver lobes were measured using regions-of-interest (ROIs) approach. Three ROIs were drawn on the fat-fraction images and duplicated on to the co-registered T2* images at the inferior right, superior right and superior left liver lobes. Comparison and validation of water-fat MRI and MRS were performed using intraclass correlation coefficient (ICC) and Bland-Altman plot. Hepatic fat-fraction and T2* measured from the ROIs were compared using repeated measures ANOVA. Independent t-test was used for between groups analysis. RESULTS: Statistical analysis indicated good correlation (R = 0.987) and agreement (ICC = 0.982) between MRS and water-fat MRI in hepatic fat measurements. Results indicated that hepatic fat was significantly higher in the right lobe compared to the left in NAFLD adults (p < 0.001) and NAFLD teenagers (p < 0.001). For T2*, significant difference between left and right lobes was observed in NAFLD adults (p < 0.001) and non-NAFLD adults (p < 0.001) but not in teenagers. CONCLUSION: Hepatic fat measurements using MRS and water-fat MRI are statistically equivalent. In subjects with NAFLD regardless of their age, hepatic fat is stored preferentially in the right live lobe probably due to the streamline of blood flow to the right liver. T2* value is significantly higher in the right liver lobe in adults but not in the teenagers regardless of their hepatic fat contents probably due to the longer time span of hepatic iron accumulation.

Robotic-assisted minimally invasive esophagectomy for treatment of esophageal carcinoma.

Minimally invasive esophagectomy (MIE) is technically challenging. Da Vinci Robotic system could improve surgical dissection with additional degree of freedom from robotic arms. This study aimed to assess the feasibility and safety of performing MIE using Da Vinci Robotic system among patients with esophageal cancers. From 2009 to 2013, consecutive patients with esophageal cancers who received robotic-assisted MIE were recruited. We excluded tumors with suspected invasion to adjacent organs. Preoperative staging included EUS, CT thorax and abdomen and bronchoscopy. We perform mobilization of thoracic esophagus with two-field lymphadenectomy using robotic system, followed by laparoscopic gastric mobilization and hand-sewn cervical esophagogastric anastomosis. A total of 20 patients were recruited (16 male and 4 female) with mean age of 64.2 ± 8.8 years. All patients were successfully treated with robotic-assisted MIE with mean operative time of 499.5 ± 70 min and blood loss of 355.7 ± 329.6 mls. There was no pulmonary complication, while three patients sustained anastomotic leakage and managed conservatively. The mean hospital stay was 13 ± 6 days. Five patients had stage I tumors, five had stage II, and nine had stage III disease. One patient had complete response after neoadjuvant chemoradiotherapy. The number of lymph node dissection was 18.2 ± 13.2, and 2.8 ± 5.7 nodes involved. The follow-up period was 21 ± 9 months, and the overall survival was 75 %. Robotic-assisted MIE is feasible and safe for treatment of esophageal cancers. The surgical dissection can be enhanced by improved ergonomics from robotic arms and sense of depth from 3D images.

Health-Related Quality of Life after Bariatric Surgery and its Correlation with Glycaemic Status in Hong Kong Chinese Adults.

BACKGROUND: To evaluate health-related quality of life (HRQOL) following bariatric surgery and its correlation with different glycaemic status in Hong Kong Chinese adults. MATERIALS AND METHODS: In 2002-2008, obese Chinese adults were recruited for bariatric surgery, undergoing laparoscopic adjustable gastric banding or laparoscopic sleeve gastrectomy. Patients were invited to complete the Chinese Hong Kong Medical Outcomes Study Short-Form Health Survey (SF-36) at baseline and at 1-year post operation. RESULTS: Sixty patients (60 % female) completed baseline and 1-year follow-up HRQOL assessments. Mean age was 38 years and mean BMI was 41.6 kg/m(2). At baseline, 30.0 % of patients had diabetes and 31.7 % prediabetes. Mean absolute weight reduction 1 year after bariatric surgery was 19.8 kg. Statistically significant improvements in SF-36 scores were demonstrated in all physical domains and in three of the four psychological domains. Greater body weight reduction was associated with greater improvements in certain physical domains postoperatively. After adjusting for co-variables, abnormal glucose tolerance was associated with greater improvements in five of the eight HRQOL domains. CONCLUSIONS: Bariatric surgery resulted in significant gains in HRQOL as well as significant reductions in body weight in obese Chinese adults. This study suggests that bariatric surgery offers greater HRQOL improvements in patients with prediabetes and diabetes compared with normoglycaemic individuals.

Predicting success of metabolic surgery: age, body mass index, C-peptide, and duration score.

BACKGROUND: Surgery is the most effective treatment of morbid obesity and leads to dramatic improvements in type 2 diabetes mellitus (T2DM). Gastrointestinal metabolic surgery has been proposed as a treatment option for T2DM. However, a grading system to categorize and predict the outcome of metabolic surgery is lacking. The study setting was a tertiary referral hospital (Taoyuan City, Taoyuan County, Taiwan). METHODS: We first evaluated 63 patients and identified 4 factors that predicted the success of T2DM remission after bariatric surgery in this cohort: body mass index, C-peptide level, T2DM duration, and patient age. We used these variables to construct the Diabetes Surgery Score, a multidimensional 10-point scale along which greater scores indicate a better chance of T2DM remission. We then validated the index in a prospective collected cohort of 176 patients, using remission of T2DM at 1 year after surgery as the outcome variable. RESULTS: A total of 48 T2DM remissions occurred among the 63 patients and 115 remissions (65.3%) in the validation cohort. Patients with T2DM remission after surgery had a greater Diabetes Surgery Score than those without (8 ± 4 versus 4 ± 4, P < .05). Patients with a greater Diabetes Surgery Score also had a greater rate of success with T2DM remission (from 33% at score 0 to 100% at score 10); A 1-point increase in the Diabetes Surgery Score translated to an absolute 6.7% in the success rate. CONCLUSION: The Diabetes Surgery Score is a simple multidimensional grading system that can predict the success of T2DM treatment using bariatric surgery among patients with inadequately controlled T2DM.

Laparoscopic repair of giant hiatus hernia: prosthesis is not required for successful outcome.

BACKGROUND: Giant hiatus hernia (GHH) are difficult to manage effectively. This study reports a laparoscopic, prosthesis-free technique to repair of GHH. METHODS: Retrospective analysis of a prospectively populated database of a single surgeon's experience of GHH (>30 % intrathoracic stomach) repair using a novel, uniform technique was performed. Routine postoperative endoscopy, quality of life (QOL), and Visick scoring was conducted. RESULTS: Surgery was conducted in 100 patients (70F, 30 M). Mean (standard deviation [SD]) age was 69.1 (±11.4), median (interquartile range) ASA was 2 (range, 2-3), and mean (SD) body mass index (BMI) was 29.1 (±4.5). Mean follow-up was 574.1 (±240.5) days. One (1 %) patient was converted to an open procedure due to technical issues. Median stay was 2.5 days (range, 2-4). One postoperative death occurred secondary to respiratory sepsis. Eight (8 %) patients had perioperative complications: 4 major (PE, non-ST elevation MI, postoperative bleed managed conservatively, infected mediastinal fluid collection); and 4 minor (pneumothorax, asymptomatic troponin leak, subacute small bowel obstruction, and urinary retention). Ninety-nine (99 %) patients had objective screening for recurrence at 3-6 months. Two (2 %) patients have had symptomatic recurrence of their hiatus hernia; both involved a recurrent fundal herniation. Another seven (7 %) had small (<2 cm), asymptomatic recurrences diagnosed only on routine follow-up. Seven (7 %) patients have required reintervention for dysphagia with endoscopic dilatation conducted to good effect in all cases. Two (2 %) patients have required revisional surgery: one for a symptomatic recurrence at 3 months and a second for recurrent mediastinal collection. The Visick score fell from a mean (SD) of 3 (±1.1) to 1.7 (±0.8) postoperatively (p < 0.0001). The mean (SD) QOL preoperatively was 87.8 (±24) versus 109.1 (±22.3) postoperatively (p < 0.0001). CONCLUSIONS: GHH can be managed safely and effectively laparoscopically, without the use of a prosthesis.