Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial

Research Problem: Surgical stress induces inflammation and postoperative immuno-suppression, which are risk. factors for both post-operative complication and possible disease recurrence. Colorectal cancer is in the top 5 malignancies in the Kingdome and the highest incidence in males. Recurrent disease locally or distally occurs in 35% of patients and is the leading cause of death in these patients. Despite the new era of laparoscopic surgery, still surgical stress is present and equally traumatic to the conventional open colorectal resection, earlier studies showed no major differences in post-operative inflammatory and immunological reactions. The previous studies revealed the anti-inflammatory effects of the hyper-insulinimic euglycemic therapy. Benefits observed in both major liver resection and in cardiac surgery. The anti-inflammatory effect reduced the surgical stress and postoperative inflammation. The hypothesis is "Can intraoperative hyper-insulinimic euglycemic infusion reduce post operative inflammation and immunomodulation in colon cancer patients undergoing a curative surgery?" Research methodology Triple blinded randomized controlled study with estimated sample size of 144 patients of non-metastatic colorectal cancer patients operated at King Saud University Medical city with a confirmed diagnosis of colon adenocarcinoma. Patients Consented will undergo computer randomization to receive intraoperative hyper-insulinimic normoglycemic infusion (experimental) or standardized insulin sliding scale and saline (control). A common preoperative and postoperative pathway with standardized management and pain control in both groups. Outcomes will be measured via a battery of laboratory test consist of routine labs, inflammatory markers and immunological markers to be repeated at fixed timed intervals. All patients will be followed by regularly for 5 years. Research objectives Primary outcomes to examine: * The anti-inflammatory effects of intraoperative hyper-insulinimic euglycemic therapy in patients undergoing colorectal cancer surgery. * The immunomodulatory effect of intraoperative hyper-insulinimic euglycemic infusion Secondary outcomes: * Thirty days post-operative morbidity. * Overall survival rate. * Disease-free survival rate.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Age \> 18 years
* Documented CRC by histopathology

Exclusion Criteria:

* Patient not consenting to the study or refused.
* Metastatic disease at the time of diagnosis.
* Contraindications to insulin
* Pregnancy

• BACKGROUNDOberhofer D, Rumenjak V, Lazic J, Vucic N. [Inflammatory indicators in patients after surgery of the large intestine]. Acta Med Croatica. 2006 Dec;60(5):429-33. Croatian. PMID 17217098
• BACKGROUNDGalizia G, Gemei M, Orditura M, Romano C, Zamboli A, Castellano P, Mabilia A, Auricchio A, De Vita F, Del Vecchio L, Lieto E. Postoperative detection of circulating tumor cells predicts tumor recurrence in colorectal cancer patients. J Gastrointest Surg. 2013 Oct;17(10):1809-18. doi: 10.1007/s11605-013-2258-6. Epub 2013 Jun 28. PMID 23813048
• BACKGROUNDRahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, Diener MK, Buchler MW, Koch M, Weitz J. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010 May;138(5):1714-26. doi: 10.1053/j.gastro.2010.01.008. Epub 2010 Jan 25. PMID 20100481
• BACKGROUNDLaw WL, Choi HK, Lee YM, Ho JW. The impact of postoperative complications on long-term outcomes following curative resection for colorectal cancer. Ann Surg Oncol. 2007 Sep;14(9):2559-66. doi: 10.1245/s10434-007-9434-4. Epub 2007 May 24. PMID 17522945
• BACKGROUNDDeng HP, Chai JK. The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis. Int Immunopharmacol. 2009 Oct;9(11):1251-9. doi: 10.1016/j.intimp.2009.07.009. Epub 2009 Jul 30. PMID 19647101
• BACKGROUNDAlbacker T, Carvalho G, Schricker T, Lachapelle K. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients. Ann Thorac Surg. 2008 Jul;86(1):20-7. doi: 10.1016/j.athoracsur.2008.03.046. PMID 18573392
• BACKGROUNDSato H, Carvalho G, Sato T, Bracco D, Codere-Maruyama T, Lattermann R, Hatzakorzian R, Matsukawa T, Schricker T. Perioperative tight glucose control with hyperinsulinemic-normoglycemic clamp technique in cardiac surgery. Nutrition. 2010 Nov-Dec;26(11-12):1122-9. doi: 10.1016/j.nut.2009.10.005. Epub 2010 Jan 25.