Sarcopenia assessed with DXA and CT increases the risk of perioperative complications in patients with gastrectomy.

OBJECTIVES: We investigated sarcopenia prevalence using various diagnostic criteria based on dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) in gastric cancer patients who underwent gastrectomy, and evaluated the association between sarcopenia and perioperative complications. METHODS: This retrospective study included consecutive patients with gastric cancer who underwent gastrectomy, and preoperative DXA and CT from January 2013 to November 2020. Body composition was measured using DXA and CT. Height-adjusted DXA-based Appendicular Skeletal Muscle Mass Index (ASMI) and CT-based skeletal muscle cross-sectional area at the L3 level (SMI) were measured. Sarcopenia and sarcopenic obesity were defined using reported cutoff values. The chi-square test and univariate analysis were performed to determine risk factors for significant and severe perioperative complications (Clavien-Dindo Grades ≥ 2 and ≥ 3, respectively). RESULTS: In total, 77 males and 43 females aged 61.4 ± 11.0 years were included. ASMI and SMI were correlated (r = 0.819), but sarcopenia prevalence varied (20.0-63.3%), depending on the criteria applied. Univariate analysis revealed sarcopenia defined using the Asian Working Group on Sarcopenia (AWGS) criteria and sarcopenic obesity as risk factors for significant (odds ratio [OR] 2.76, p = 0.030 vs. OR 4.31, p = 0.002) and severe perioperative complications (OR 3.77, p = 0.036 vs. OR 4.78, p = 0.010). In subgroup analyses, sarcopenia and sarcopenic obesity were significantly associated with perioperative complications only in males. CONCLUSION: Perioperative complication risk can be predicted from sarcopenia defined using the AWGS criteria and sarcopenic obesity measured using DXA and CT, particularly in males. KEY POINTS: • The prevalence of sarcopenia varies due to definition differences. • Sarcopenia and sarcopenic obesity are risk factors for significant and severe perioperative complications, particularly in males. • Our results suggest that physicians need to pay attention to perioperative complications after surgical treatment of male patients with sarcopenia and sarcopenic obesity.

Short-term changes in the serum metabolome after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported. OBJECTIVES: The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities. METHODS: Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis. RESULTS: Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB. CONCLUSION: These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.

Changes in lipid indices and body composition one year after laparoscopic gastrectomy: a prospective study.

BACKGROUND: The purpose of this prospective study was to investigate changes in lipid indices associated with whole body composition during 1 year of follow-up after laparoscopic gastrectomy. METHODS: Thirty-seven patients with benign and malignant gastric neoplasm who underwent laparoscopic gastrectomy were prospectively enrolled. None of the patients were treated with adjuvant chemotherapy. Lipid indices and body composition were measured preoperatively and at six and 12 months after laparoscopic gastrectomy. Lipid indices included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Body weight, fat and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry and the change in fat and LBM in the trunk, arms and legs was compared. RESULTS: Body weight significantly decreased from 63.0 ± 11.1 kg preoperatively to 56.8 ± 10.6 kg 12 months after laparoscopic gastrectomy, with a mean of 7.1% (4.6 kg) weight loss. Fat and LBM loss contributed 68.4% (3.1 kg) and 30.1% (1.4 kg) of the total weight loss, respectively. In both the non-obese and obese groups, body weight, fat and LBM did not change significantly between 6 months and 12 months after gastrectomy. TC and LDL-C levels significantly decreased during the first six-month period and HDL-C significantly increased until 12 months after gastrectomy in the non-obese group. In the obese group, the degree of reduction in fat mass was significantly higher and the LBM/weight ratio significantly increased compared with the non-obese group. However, there was no significant change in lipid indices in the obese group. The TG level was significantly correlated with fat, especially with trunk fat. CONCLUSION: Gastrectomy resulted in improved lipid indices and a reduction in body weight, fat and LBM. The HDL-C significantly increased in the non-obese group for 1 year after gastrectomy and the reduction of TG level was positively correlated with fat, especially with trunk fat (IRB No. 2015-04-026. Registered 4 May 2015).

Thyroidectomy stimulates glucagon-like peptide-1 secretion and attenuates hepatic steatosis in high-fat fed rats.

Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low-density lipoprotein in HN Thx. Unexpectedly, however, Thx reduced serum and hepatic triglyceride concentrations. Further studies revealed that Thx dramatically increased circulating GLP-1 as well as increased expressions of GLP-1 in small intestine. Diminished hepatic expressions of lipogenic genes, were observed in HN Thx group. Beta-catenin and glutamine synthetase, a known target of ß-catenin, were up-regulated in the liver of HN Thx group. The expressions of gluconeogenic genes G6P and PCK were reduced in the liver of HN Thx group. The results may suggest that surgery-induced hypothyroidism increases GLP-1, the actions of which may in part be responsible for the reduction in water intake, appetite and hepatic steatosis.

Changes in one-carbon metabolism after duodenal-jejunal bypass surgery.

Bariatric surgery alleviates obesity and ameliorates glucose tolerance. Using metabolomic and proteomic profiles, we evaluated metabolic changes in serum and liver tissue after duodenal-jejunal bypass (DJB) surgery in rats fed a normal chow diet. We found that the levels of vitamin B12 in the sera of DJB rates were decreased. In the liver of DJB rats, betaine-homocysteine S-methyltransferase levels were decreased, whereas serine, cystathionine, cysteine, glutathione, cystathionine ß-synthase, glutathione S-transferase, and aldehyde dehydrogenase levels were increased. These results suggested that DJB surgery enhanced trans-sulfuration and its consecutive reactions such as detoxification and the scavenging activities of reactive oxygen species. In addition, DJB rats showed higher levels of purine metabolites such as ATP, ADP, AMP, and inosine monophosphate. Decreased guanine deaminase, as well as lower levels of hypoxanthine, indicated that DJB surgery limited the purine degradation process. In particular, the AMP/ATP ratio and phosphorylation of AMP-activated protein kinase increased after DJB surgery, which led to enhanced energy production and increased catabolic pathway activity, such as fatty acid oxidation and glucose transport. This study shows that bariatric surgery altered trans-sulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery.

Multicenter Prospective Comparative Study of Robotic Versus Laparoscopic Gastrectomy for Gastric Adenocarcinoma.

OBJECTIVE: To compare short-term surgical outcomes including financial cost of robotic and laparoscopic gastrectomy. BACKGROUND: Despite a lack of supporting evidence, robotic surgery has been increasingly adopted as a minimally invasive modality for the treatment of gastric cancer because of its assumed technical superiority over conventional laparoscopy. METHODS: A prospective, multicenter comparative study was conducted. Patients were matched according to the surgeon, extent of gastric resection, and sex. The primary endpoint was morbidity and mortality. Outcomes were analyzed on an intention-to-treat and per-protocol basis. RESULTS: A total of 434 patients were enrolled for treatment with either robotic (n = 223) or laparoscopic (n = 211) gastrectomy for intention-to-treat analysis, and a total of 370 patients (n = 185 per treatment) were compared in per-protocol analysis. Results were similar between both analyses. In per-protocol analysis, both groups showed similar overall complication rates (robotic = 11.9% vs laparoscopic = 10.3%) and major complication rates (robotic = 1.1% vs laparoscopic = 1.1%) with no operative mortality in either group. Patients treated with robotic surgery showed significantly longer operative time (robotic = 221 minutes vs laparoscopic = 178 minutes; P < 0.001) and significantly higher total costs (robotic = US$13,432 vs laparoscopic = US$8090; P < 0.001), compared with those who underwent laparoscopic gastrectomy. No significant differences between groups were noted in estimated blood loss, rates of open conversion, diet build-up, or length of hospital stay. CONCLUSIONS: The use of robotic systems is assumed to provide a technically superior operative environment for minimally invasive surgery. However, our analysis of perioperative surgical outcomes indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. Clinical trials identification: NCT01309256.

Discordant findings between preoperative endoscopy and postoperative pathology as an independent prognostic factor in gastric cancer patients.

BACKGROUND: Endoscopically diagnosed early gastric cancers (EGCs) are sometimes revealed to be advanced gastric cancers (AGCs) on pathologic examination of the resected specimen, and also endoscopically diagnosed AGCs are often determined to be EGCs. This study was designed to determine the impact on prognosis of the discordant finding between preoperative endoscopy and postoperative pathology in gastric cancer patients. METHODS: Patients with gastric cancer stages pT1a-T4a who underwent curative gastrectomy between 2004 and 2010 were included in the study. The preoperative endoscopic findings and clinicopathologic features were analyzed. The prognostic impact on recurrence-free survival of discordance between endoscopic and pathologic examinations was analyzed using multivariate analysis. RESULTS: Among 367 patients diagnosed with EGC on preoperative endoscopy, 40 (11 %) had AGC on final pathologic examination; this was more common in female patients, upper one-third location of the cancer, poorly differentiated tumor, combined gross type (elevated and depressed), lymphovascular invasion and lymph node metastasis. Among 350 patients diagnosed with AGC on preoperative endoscopy, 66 (19 %) had EGC pathologically; this was more frequent in patients with tumor in the lower and/or middle third of the stomach, differentiated tumor, Borrmann type 1 and absence of lymph node metastasis. The endoscopic appearance of AGC was identified as a poor prognostic factor related to recurrence-free survival in patients with EGC, whereas discordance did not influence recurrence-free survival in patients with AGC. CONCLUSIONS: Discordant preoperative endoscopic appearance may be an indicator of biologic aggressiveness and a reliable prognostic factor in EGC, but not in AGC.

Roux-en-Y gastric bypass stimulates hypothalamic miR-122 and inhibits cardiac and hepatic miR-122 expressions.

BACKGROUND: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB). METHODS: Male Sprague-Dawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphate-activated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results. RESULTS: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK. CONCLUSIONS: The results in this study suggest that RYGB regulates the expressions of miR-122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism.

Metabolic effects of gastrectomy with or without omentectomy in gastric cancer.

BACKGROUND/AIMS: The metabolic effects of gastrectomy and the reduction of visceral adiposity through omentectomy for gastric cancer are unknown. METHODOLOGY: We retrospectively reviewed of prospectively collected data of 67 patients over one year who underwent radical gastrectomy with either a complete or partial omentectomy for gastric cancer. The change in Body mass index (BMI), triglyceride, low density lipoprotein, high density lipoprotein, and hematological profile were evaluated. RESULTS: In the group of 67 patients changes were observed after 1 year follow-up for BMI (23.7±3.1 versus 21.3±2.5kg/m2; p<0.001), triglyceride (155.2±136.1 versus 89.7±41.2mg/dL, p=0.011), low density lipoprotein (107.4±45.4 versus 95.8±27.5mg/dL, p=0.020), vitamin B12 (681.4±297.4 versus 558.1±338.6pg/mL, p=0.076). High density lipoprotein (41.4±12.6 versus 52.8±10.5mg/dL) increased after surgery (p<0.001). There were no changes between the complete and partial omentectomy groups for BMI, albumin, triglyceride, lipoprotein, and hemoglobin. CONCLUSIONS: Gastrectomy with or without omentectomy induced a decrease of BMI and improvements in metabolic parameters such as triglyceride, low density lipoprotein, high density lipoprotein. Omentectomy had no significant impact on any measured parameter in this group.

The primary extra-gastrointestinal stromal tumor of pleura: a case report and a literature review.

The gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. The gastrointestinal stromal tumor universally expresses KIT and DOG-1 and frequently harbors oncogenic mutations in the KIT gene. While the gastrointestinal stromal tumor usually arises in the alimentary tract, it is rarely found in the extragastrointestinal area. When it is, it is called an extragastrointestinal stromal tumor. Although the pathogenesis, prognostic factors and outcomes of gastrointestinal stromal tumors are well known, those of extragastrointestinal stromal tumors have not been fully studied. We report, herein, a unique primary extragastrointestinal stromal tumor from the pleura in a 73-year-old woman who presented with pleural mass. The extragastrointestinal stromal tumor was surgically resected and confirmed by means of an immunohistochemical study and a molecular analysis.

Laparoscopic Sleeve Gastrectomy in a Morbidly Obese Pediatric Patient With Bardet-Biedl Syndrome.

Data on the effect of bariatric surgery for syndromic obesity are lacking. This case report presents the preoperative evaluation and perioperative outcomes of a 7-year-old pediatric patient with Bardet-Biedl syndrome (BBS) who underwent sleeve gastrectomy. The male patient was referred to our department for the surgical treatment of his obesity. His preoperative body mass index (BMI) was 55.2 kg/m2 (weight, 83.5 kg), and he was above the 99th percentile for age and gender. The patient underwent laparoscopic sleeve gastrectomy. The postoperative period was uneventful. Six months after the operation, the patient's weight decreased to 50 kg (BMI, 28.72 kg/m2). Weight loss was maintained until 3 years after surgery. Dyslipidemia and nonalcoholic fatty liver disease were significantly alleviated. Laparoscopic sleeve gastrectomy may be a safe and effective treatment for morbid BBS-related obesity in pediatric patients. Further data are needed to confirm the long-term efficacy and safety of bariatric surgery in BBS.

Effects of sitagliptin on peritoneal membrane: The potential role of mesothelial cell tight junction proteins.

BACKGROUND: The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology. METHODS: Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression. RESULTS: In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-ß treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-ß treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-ß treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats. CONCLUSION: The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.

Pattern analysis of lymph node metastasis and the prognostic importance of number of metastatic nodes in ampullary adenocarcinoma.

The aims of this study were to clarify the distribution and spread pattern of metastatic nodes and to evaluate the importance of the number, ratio, and location of positive nodes in ampullary adenocarcinoma. We analyzed the clinicopathologic data and survival of 52 patients who received curative pancreatoduodenectomy for ampullary adenocarcinoma between June 1994 and May 2009. Metastatic lymph nodes were found in 32 (61.5%) patients. The median number of evaluated nodes and positive nodes were 26 (range 10-60) and two (range 1-15), respectively. The most commonly involved nodes were the posterior pancreaticoduodenal nodes (26 patients) followed by the anterior pancreaticoduodenal nodes (11 patients). No positive hepatoduodenal and common hepatic artery nodes were found. In univariate analysis, number of positive nodes, and their ratio and location were significantly associated with survival. Only the factor of three or more metastatic nodes had the independent power in predicting a poor outcome in multivariate analysis (P < 0.001). Ampullary adenocarcinoma first spreads to the posterior pancreaticoduodenal nodes and then the anterior nodes. The number of positive lymph nodes, rather than their ratio and location, independently affects survival after curative resection in patients with ampullary carcinoma.

Changes in Trimethylamine-N-oxide Levels in Obese Patients following Laparoscopic Roux-en-Y Gastric Bypass or Sleeve Gastrectomy in a Korean Obesity Surgical Treatment Study (KOBESS).

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

Duodenal-jejunal bypass maintains hepatic S-adenosylmethionine/S-homocysteine ratio in diet-induced obese rats.

We previously reported that the duodenal-jejunal bypass (DJB) surgery altered transsulfuration and purine metabolism via flux changes in 1-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB group) interventions. The microscopic features of the liver were examined by immunohistochemistry. The expressions of genes in lipid synthesis and in 1-carbon cycle in the liver were analyzed by real-time polymerase chain reaction and western blotting. Metabolic changes in the liver were determined. We observed that DJB reduces hepatic steatosis and improves insulin sensitivity in both high-fat diet-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased S-adenosylmethionine (SAM)-to-S-adenosylhomocysteine ratio via downregulation of SAM synthesizing enzyme and upregulation of SAM catabolizing enzyme. We also found in mice that DJB-mediated attenuation of hepatic steatosis is independent of weight loss. DJB also increased hepatic expression levels of GNMT while decreasing those of PEMT and BHMT, a change in 1-carbon metabolism that may decrease the ratio of SAM to S-adenosylhomocysteine, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in 1-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery.

Bariatric surgery versus medical therapy in Korean obese patients: prospective multicenter nonrandomized controlled trial (KOBESS trial).

PURPOSE: The aim of this study was to show that bariatric surgery (BS) is more effective than medical therapy (MT) in Asian obese patients. METHODS: In this prospective, multicenter, nonrandomized, controlled trial, obese patients with body mass index of ≥35 kg/m2 or 30.0-34.9 kg/m2 with obesity-related comorbidities were assigned to undergo BS, such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, or MT. Patients who underwent BS were evaluated 4, 12, 24, and 48 weeks after surgery, whereas patients who received MT were monitored at a hospital every 6 weeks for 1 year. At each visit, weight, waist and hip circumference, and blood pressure were measured, and patients underwent physical examination and laboratory testing. Health-related quality of life (HQOL) was investigated using Euro QOL-5 Dimension, Impact of Weight on Quality of Life questionnaire-Lite and Obesity-related Problems scale. RESULTS: The study included 264 patients from 13 institutions; of these, 64 underwent BS and 200 received MT. Of the patients who underwent BS, 6.3% experienced early complications. Relative weight changes from baseline to 48 weeks were significantly greater in the BS than in the MT group (26.9% vs. 2.1%, P < 0.001), as were the rates of remission of diabetes (47.8% vs. 16.7%, P = 0.014), hypertension (60.0% vs. 26.1%, P < 0.001), and dyslipidemia (63.2% vs. 22.0%, P < 0.001). HQOL was better in the BS than in the MT group at 48 weeks. CONCLUSION: BS was safe and effective in Korean obese patients, with greater weight reduction, remission of comorbidities, and quality of life improvement than MT.

Prediction of Long-Term Diabetes Remission After Metabolic Surgery in Obese East Asian Patients: a Comparison Between ABCD and IMS Scores.

PURPOSE: Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial. METHODS: Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients. RESULTS: The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG. CONCLUSION: IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.

Differential effects of 5-fluorouracil on glucose transport and expressions of glucose transporter proteins in gastric cancer cells.

Although 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent in the treatment of gastric cancer, the underlying mechanism for 5-FU resistant phenotype, has yet to be elucidated. We hypothesized that the sensitivity of gastric cancer to 5-FU treatment might be related to the rate of glucose transport (GLUT), and investigated the expressions of GLUT1, 2, 3, and 4 in two different gastric cancer cells (SNU-216, moderately differentiated gastric adenocarcinoma; and SNU-668, signet ring cell gastric carcinoma). Immunohistochemistry of GLUT1 and GLUT4 and immunoblot analysis of glycogen synthase kinase 3 were also performed. Hexokinase activity was measured. We found that 5-FU suppressed glucose uptake in SNU-216, while it stimulated GLUT in SNU-668. Further analysis revealed that 5-FU decreased the expression levels of GLUT1, 2, and 4 in SNU-216 cells and increased the expression levels of GLUT1, 2, and 4 in SNU-668 cells. Consistent with GLUT expression levels, immunohistochemistry analysis showed that 5-FU increased GLUT1 and GLUT4 levels in SNU-216 and decreased GLUT1 and GLUT4 levels in SNU-668. We also observed that glycogen synthase kinase 3 activity was decreased in SNU-216 and increased in SNU-668 with 5-FU treatment. No significant difference in hexokinase activities was observed with 5-FU treatment. Taken together, these results suggest that 5-FU exerts differential effects on GLUT depending on gastric cancer cell types, which may indicate a possible explanation, at least in part, for the differing responses to 5-FU chemotherapy in gastric cancer.

Pinealectomy increases thermogenesis and decreases lipogenesis.

The present study was designed to determine the effects of pineal gland­derived melatonin on obesity by employing a rat pinealectomy (Pnx) model. After 10 weeks of a high­fat diet, rats received sham or Pnx surgery followed by a normal chow diet for 10 weeks. Reverse transcription­quantitative PCR, western blotting analysis, immunohistochemistry and ELISA were used to determine the effects of Pnx. Pnx decreased the expression of melatonin receptor (MTNR)1A and MTNR1B, in brown adipose tissues (BAT) and white adipose tissues (WAT). Pnx rats showed increased insulin sensitivity compared with those that received sham surgery. Leptin levels were significantly decreased in the serum of the Pnx group. In addition, Pnx stimulated thermogenic genes in BAT and attenuated lipogenic genes in both WAT and the liver. Histological analyses revealed a marked decrease in the size of lipid droplets and increased expression of uncoupling protein 1 in BAT. In the liver of the Pnx group, the size and number of lipid droplets had also decreased. In conclusion, the results presented in the current study suggested that Pnx increases thermogenesis in BAT and decreases lipogenesis in WAT and the liver.