Safety and Efficacy of Long Limb Roux-en Y Reconstruction (LoLiRoRe)

• Morbidity [ Time Frame: Until end of study (on average 14.8 months) ] [ Designated as safety issue: Yes ]

  For the evaluation of safety, morbidity were analyzed. For the evaluation of short-term safety, complications higher than the Clavien-Dindo grade II (Dindo et. Ann Surg 240:205 2004) were collected.

  *Clavien-dindo classification of surgical complications Grade II: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.

  Grade III: Requiring surgical, endoscopic or radiological intervention Grade IV:Life-threatening complication (including CNS complications)‡ requiring IC/ICU-management Grade V:Death of a patient Suffix'd' : If the patient suffers from a complication at the time of discharge ,the suffix "d" (for 'disability') is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication.

  For the evaluation of long-term safety, the patients were evaluated every month after discharge.

• HbA1c [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  For the evaluation of efficacy for the operation, HbA1c(%) was measured serially (preop. 6months after op. until end of study(on average 14.8 months)).

  HbA1c is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose and measured by high-performance liquid chromatography (HPLC) The HbA1c was calculated as a ratio to total hemoglobin.

• Hemoglobin [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]
  For the evaluation of long-term safety, hemoglobin was measured to determine the degree of anemia and malnutrition.
• Albumin [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]
  For the evaluation of long-term safety, albumin was measured to determine malnutrition.
• Operation Related Mortality [ Time Frame: Until end of study (on average 14.8 months) ] [ Designated as safety issue: Yes ]
  Operation related mortality was measured for the evaluation of safety for the operation. Operation related mortality was defined as any complication resulting in the death of the patient within 1 month or during hospitalization after operation.

• Matsuda Index [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  Matsuda Index(Insulin Sensitivity Index) was measured.

  The Matsuda index was obtained using the following formula:

  Matsuda index = 10000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin during OGTT)]

• QUICKI [ Time Frame: Before operation , 6 months after operation , Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  The quantitative insulin sensitivity check index (QUICKI) was measured.

  The QUICKI was obtained using the following formula:

  1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL))

• HOMA-IR [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  HOMA-IR(Homeostasis model assessment-estimated insulin resistance) was measured.

  HOMA-IR was obtained using the following formula:

  Glucose(mg/dl) x Insulin/405

• HOMA-B [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  HOMA-B(Homoeostasis model assessment-derived beta-cell function) was measured.

  HOMA-B was obtained using the following formula:

  225 × 18/fasting insulin(mU/L) × fasting glucose(mg/dL)

• Body Mass Index [ Time Frame: Before operation, 6 Months After Operation, Until End of Study(on Average 14.8 Months) ] [ Designated as safety issue: No ]

  BMI(Body Mass index , kg/㎡) was measured.

  BMI was obtained using the following formula:

  Weight (kg) / (Height (m) x Height (m))

• Matsuda Index : Good Response Group [ Time Frame: Before operation , 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications after operation. We called this group as "good response group". We analyzed the change of insulin sensitivity after operation in good response group.

  The Matsuda index(Insulin Sensitivity Index) was obtained using the following formula:

  Matsuda index = 10000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin during OGTT)]

• QUICKI : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of insulin sensitivity after operation in good response group. The quantitative insulin sensitivity check index (QUICKI) was measured.

  The QUICKI is obtained using the following formula:

  1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL))

• HOMA-IR : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of insulin resistance after operation in good response group.

  HOMA-IR(Homeostasis model assessment-estimated insulin resistance) was measured.

  HOMA-IR was obtained using the following formula:

  Glucose(mg/dl) x Insulin/405

• HOMA-B : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of beta-cell function after operation in good response group. HOMA-B(Homoeostasis model assessment-derived beta-cell function) was measured.

  HOMA-B was obtained using the following formula:

  225 × 18/fasting insulin(mU/L) × fasting glucose(mg/dL)

• Body Mass Index : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of weight change after operation in good response group.

  BMI(Body Mass index , kg/㎡) was measured.

  BMI was obtained using the following formula:

  Weight (kg) / (Height (m) x Height (m))

• HbA1c : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]

  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of HbA1c after operation in good response group.

  HbA1c is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose and measured by high-performance liquid chromatography (HPLC)

  The HbA1c was calculated as a ratio to total hemoglobin.

• Hemoglobin : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]
  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". For the evaluation of long-term safety, hemoglobin was measured to determine the degree of anemia and malnutrition in good response group.
• Albumin : Good Response Group [ Time Frame: Before operation, 6 months after operation, Until end of study (on average 14.8 months) ] [ Designated as safety issue: No ]
  At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of albumin level after operation in good response group for the evaluation of long-term safety.

We grafted the concept of metabolic surgery (long limb Roux-en Y reconstruction) into gastric cancer surgery. This study aimed to investigate the safety and efficacy of long limb Roux-en Y reconstruction after gastrectomy in non-obese type II diabetes with gastric cancer.

Type II diabetes in the world is increasing rapidly, and it is known that patients with type II diabetes with morbid obesity that underwent bariatric surgery have resolution of impaired glucose metabolism.

In Asia, most type II diabetes are not morbidly obese and still, it is controversy whether metabolic surgery is effective or not in non-morbid obese patients. As life expectancy is increased, the number of patients with gastric cancer and T2DM is increased as well.

Recently, we studied the outcome of T2DM after gastrectomy and conventional reconstruction in non-obese gastric cancer patients.(Kim JW et al, World J Gastroenterol 2012;18:49) The study was a large-series retrospective study including about 400 patients and the result regarding DM improvement was not satisfactory. Based on our previous results, it is needed to find more effective way to resolve the type II diabetes in gastrectomized patients with gastric cancer.

• Diabetes Mellitus Type 2 in Nonobese
• Gastric Cancer

• Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. Review.
• Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2.
• Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, Zimmet P, Son HY. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006 Nov 11;368(9548):1681-8. Review.
• FRIEDMAN MN, SANCETTA AJ, MAGOVERN GJ. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg Gynecol Obstet. 1955 Feb;100(2):201-4.
• ANGERVALL L, DOTEVALL G, TILLANDER H. Amelioration of diabetes mellitus following gastric resection. Acta Med Scand. 1961 Jun;169:743-8.
• Yang J, Li C, Liu H, Gu H, Chen P, Liu B. Effects of subtotal gastrectomy and Roux-en-Y gastrojejunostomy on the clinical outcome of type 2 diabetes mellitus. J Surg Res. 2010 Nov;164(1):e67-71. Epub 2010 Jul 30.
• Kim JW, Cheong JH, Hyung WJ, Choi SH, Noh SH. Outcome after gastrectomy in gastric cancer patients with type 2 diabetes. World J Gastroenterol. 2012 Jan 7;18(1):49-54.
• DeFronzo RA, Matsuda M. Reduced time points to calculate the composite index. Diabetes Care. 2010 Jul;33(7):e93.
• Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, Shoji T, Okuno Y, Morii H. Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care. 1999 May;22(5):818-22.
• Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10.
• Frenken M, Cho EY, Karcz WK, Grueneberger J, Kuesters S. Improvement of type 2 diabetes mellitus in obese and non-obese patients after the duodenal switch operation. J Obes. 2011;2011:860169. Epub 2011 Mar 3.
• Cohen R, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m(2): a tailored approach. Surg Obes Relat Dis. 2006 May-Jun;2(3):401-4, discussion 404.
• DePaula AL, Macedo AL, Mota BR, Schraibman V. Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI 21-29. Surg Endosc. 2009 Jun;23(6):1313-20. Epub 2008 Oct 2.
• Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases. Surg Obes Relat Dis. 2007 Mar-Apr;3(2):195-7.
• Orci L, Chilcott M, Huber O. Short versus long Roux-limb length in Roux-en-Y gastric bypass surgery for the treatment of morbid and super obesity: a systematic review of the literature. Obes Surg. 2011 Jun;21(6):797-804. Review.
• Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006 Nov;244(5):741-9.
• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13.

Inclusion Criteria:

• Pathologically confirmed gastric cancer with potentially curable state
• Non-obese (Body mass index: less than 30 kg/m2)

• Have a history of Type 2 DM over 6 months (diagnosed by ADA criteria)

  1. HBA1c: more than 6.5 %, or Fasting glucose: more than 126 mg/dl (7.0mmol/L) or 2-h plasma glucose: more than 200mg/dl during an OGTT or classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose: more than 200mg/dl
  2. Anti-GAD antibody (-), Anti-islet antibody (-)
• C-peptide level: above 1ng/ml

Exclusion Criteria:

• Patient who receive non-curative operation
• Patient who have less than one year life expectancy
• Pregnant patient
• Acute inflammation status patient
• Chronic renal disease patient (Serum creatin level: more than 1.5mg/dl)
• Chronic liver disease patient (Serum AST or ALT level: more than twice of upper limit of normal range)
• Have a history of receiving medications such as dipeptidyl peptidase IV(DPP- IV) inhibitor or glucagon like peptide-I (GLP-I) analogue