Department of General surgery TSGH Department of General surgery Clinical Course of Diabetes After Gastrectomy in Patients with Concurrent Gastric Cancer and Type 2 Diabetes Presenter: Dr. Chiu Yu-Chen Supervisor: Dr. Chan De-Chian Department of General Surgery Date: March 17th, 2018

Outline Mechanisms of the Bariatric Procedures Prevalence and risk of gastric CA with type 2 diabetes Study design Preliminary results in TSGH Conclusion

Gut hormones & Energy hemostasis Gut hormones have a number of functions, including the regulation of blood glucose levels, gastrointestinal motility and growth, exocrine secretion and adipocyte function Kevin G. Murphy NATURE December 2006

Standard metabolic operation mechanism ASMBS precise mechanisms for restoration of euglycemia after metabolic operations have only been partly elucidated Restrictive component decrease calrolic intake; Malabsorptive components including RYGB/BPD The most important incretin mechanism, improves pattern of insulin secretion, suppresses glucagon secretion, and possibly enhances peripheral glucose uptake

Rerouting of the gastrointestinal tract following diversionary metabolic operations, with exclusion of the duodenum and proximal jejunum (foregut hypothesis) , and the rapid exposure of the distal ileum to undigested nutrients (hindgut hypothesis); alters secretion of gut hormones including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which positively affects glucose homeostasis」

Diabetes Care 2016;39:861–877 2nd Diabetes Surgery Summit Metabolic surgery defined here as the use of GI surgery with the intent to treat T2D and obesityd requires the development of a diabetes-based model of clinical practice consistent with international standards of diabetes care. 7. Complementary criteria to the sole use of BMI, the traditional criterion used to select candidates for bariatric surgery, need to be developed to achieve a better patient selection algorithm for metabolic surgery. Grade U; LoC 100% 8. RYGB, VSG, LAGB, and BPD classic or duodenal switch variant (BPD-DS), are common metabolic operations, each with its own risk-to-benefit ratio. All other metabolic operations are considered to be investigational at this time.

DM Prevalence in Gastric cancer Per 100,000 population Prevalence (594/100000) 40.6% Taiwan NHI database In Taiwan NHI database, gastric cancer patient has DM was estimated around 539/ 1000000, DM rate in gastric CA 40.6% Tseng, J Clin Gastroenterol, July 2013

DM and GC Risk T. Tian Exp Clin Endocrinol Diabetes 2012 In one meta-analysis, DM seemed to be a risk factor of gastric cancer. RR was estimated around 1.16. Explanations: Hyperglycemia is associated with pro-inflammatory status, oxidative stress, impaired immune function and increased insulin secretion. All of these may contribute to the development of gastric cancer. Epidemiological studies conducted in Japan support hyperglycemia as a risk factor for gastric cancer, and an interaction between hyperglycemia and H. pylori infection. Such a link may also be supported by findings from in vitro studies T. Tian Exp Clin Endocrinol Diabetes 2012

Risk of GC development, RR:1.11 Mortality correlation, RR: 1.29 These pooling forest plot analysis indicated DM increased risk of GC developmenet; In gastric cancer subgroup analysis, mortality is higher in DM patient as well Risk of GC development, RR:1.11 Mortality correlation, RR: 1.29 T. Tian Exp Clin Endocrinol Diabetes 2012

PICOS Population: gastric cancer and Morbid obesity patients in TSGH, 2016 Intervention: Total/ distal gastrectomy with RY reconstruction Sleeve gastrectomy(control group) Comparator: DM patients Outcome: DM remission Free of insulin and oral hypoglycemic drug Study design: retrospective study

Pre-operative BMI(kg/m2) Diangosis Stomach cancer (N=59) Morbid obesity (N=14) DM Non-DM Patient characteristics P-vaule Age 74.3±12.0 65.8±13.4 0.045 49.0±11.6 42.1±12.3 0.356 Gender 0.305 0.455 Male 9 36 2 3 Female 4 7 Operative method 0.085 Subtotal gastrectomy 8 27 Total gastrectomy 6 19 Sleeve gastrectomy 10 DM medication Insulin 5 OAD 3 OAD 2 1 OAD 1 Pre-operative BMI(kg/m2) 24.9±3.7 22.7±3.2 0.046 37.7±3.5 38.2±4.7 0.428 In

Fasting glucose(mg/dl) Pre-op Postop 6 months Operative method TG (n=7) DG (n=6) SG (n=4) BMI(kg/m2) 24.2±3.6 25.6±3.9 37.7±3.5 21.7±3.8 21.8±3.3 27.5±4.8 HbA1c(%) 6.9±2.0 6.5±4.6 8.0±2.1 6.5±1.0 6.4±1.3 Fasting glucose(mg/dl) 140.4± 43.5 136.6± 26.4 154.0± 41.6 118.0± 21.9 130.5± 56.8 113.3± 28.9 After operation, sleeve gastrectomy or gastric operation all revealed BMI, HbA1c, fasting glucose reduction, but it was insigfincant in Paired T test statistically

Post OP DM status Remission Improvement Persistent DM OP method 　Gastric cancer with DM Post OP DM status p vaule Remission Improvement Persistent DM OP method Subtotal gastrectomy 2 3 0.78 Total gastrectomy 0.77 Morbid obesity Sleeve gastrectomy 1 0.89

Conclusion Diabetes mellitus increased gastric cancer mortality and development In gastric cancer patients, onco-metabolic surgery has similar impact to diabetes mellitus remission; no difference to sleeve gastrectomy as well Limitation: Small sample size, no propensity matching Short follow up duration Limited types surgery included

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