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Impact of the different biliopancreatic limb length on diabetes and incretin hormone secretion following distal gastrectomy in gastric cancer patients

ABSTRACT: The present study aimed to investigate changes in glucose metabolism and incretin hormone response following longer intestinal bypass reconstruction after distal gastrectomy (DG) in low BMI patients with gastric cancer and type 2 diabetes. A total of 20 patients were prospectively recruited and underwent either conventional Billroth I (BI), Billroth II with long-biliopancreatic limb (BII), or Roux-en-Y anastomosis with long-Roux limb (RY) after DG. A 75g-oral glucose tolerance test (OGTT) was given preoperatively; and at 5 days, 3 months, and 6 months postoperatively. Serum glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were serially measured. At 6 months after surgery, complete diabetes remission was achieved in 57.1% of the BII group but in no patients in the other two groups (p = 0.018). BII group showed a significant reduction in glucose concentration during OGTT at 6 months in contrast to the other 2 groups. In the BII group, a significant increase in GLP-1 secretion was observed after surgery but not maintained at 6 months, while postoperative hyperglucagonemia was alleviated along with a reduction in GIP. BII gastrojejunostomy with long biliopancreatic limb achieved better diabetes control with favorable incretin response after DG compared to BI or RY reconstruction.

SUBMITTER: Park J

PROVIDER: S-EPMC8599427 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion. Portosystemic gradient was used to calculate intestinal glucose utilization (Gutil), absorption (Gabsorp), and hormone secretion. Intestinal morphology and gene expression were assessed. At 2 wk, Gabsorp progressively decreased with increasing BP limb length; this pattern persisted at 4 wk. Gutil increased ?70% in both RYGB-20cm and -40cm groups at 2 wk. At 4 wk, Gutil progressively increased with limb length. Furthermore, Roux limb weight, and expression of hexokinase and preproglucagon, exhibited a similar progressive increase. At 4 wk, glucagon-like peptide-1 and -2 levels were higher after RYGB-40cm, with associated increased secretion. We conclude that BP limb length modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. Early postoperatively, a longer BP limb reduces Gabsorp. Later, Gutil, Roux limb hypertrophy, hormone secretion, and hormone levels are increased with longer BP limb. Sustained high incretin levels may prevent weight regain and T2D relapse. These data provide the basis for customizing BP limb length according to patient characteristics and desired metabolic effect. NEW & NOTEWORTHY Biliopancreatic limb length in gastric bypass modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. With a longer biliopancreatic limb, Roux limb hypertrophy, increased glucose utilization, reduced glucose absorption, and sustained high incretin levels may prevent weight regain and diabetes relapse.

Project description:Background/aimsTotal gastrectomy (TG) has shown to be superior regarding low risk of recurrence and readmission to distal subtotal gastrectomy (DG) for treatment of distal stomach cancer, but the incidence of postoperative morbidity and mortality in TG cannot be ignored. Therefore, we performed a meta-analysis to compare the effectiveness between TG and DG for distal stomach cancer.MethodologyA search in PubMed, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Database through January 2016 was performed. Eligible studies in comparing of TG and DG for distal gastric cancer were included in this meta-analysis. Review Manager 5.2 software from the Cochrane Collaboration was used for the performance of meta-analysis and STATA 12.0 software for meta-regression analysis.ResultsTen retrospective cohort studies and one randomized control trial involving 5447 patients were included. The meta-analysis showed no significant difference of postoperative mortality (RR = 1.48, 95%CI = 0. 90-2.44,p = 0.12), intraoperative blood loss (MD = 24.34, 95%CI = -3.31-51.99, p = 0.08) and length of hospital stay(MD = 0.76, 95%CI:-0.26-1.79, p = 0.15). TG procedure could retrieve more lymph nodes than DG(MD = 4.33, 95% CI = 2.34-6.31, p<0.0001). According to different postoperative complications, we performed subgroup analysis, subgroup analysis revealed that patients in TG group tended to have a higher rate of postoperative intra-abdominal abscess than DG procedure (RR = 3.41, 95% CI = 1.21-9.63,p<0.05). No statistical differences were found in leakage, intestinal obstruction, postoperative bleeding, anastomotic stricture and wound infection between the two groups (p>0.05). We pooled the data together, the accumulated 5-year Overall Survival rates of TG and DG groups were 49.6% (919/1852) vs.55.9%(721/1290) respectively. Meta-analysis revealed a favoring trend to DG procedure and there was a statistical difference between the two groups (RR = 0.91,95% CI = 0.85-0.97,p = 0.006).ConclusionBased on current retrospective evidences, we found that in spite of similar postoperative mortality, TG for distal gastric cancer provided a high risk of five-year Overall Survival rate. DG procedure can be a recommendation for distal gastric cancer, whereas due to lack of high quality RCTs in multicenter and the relatively small sample size of long-term outcomes, further comparative studies are still needed.

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Impact of the different biliopancreatic limb length on diabetes and incretin hormone secretion following distal gastrectomy in gastric cancer patients

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