Perioperative Blood Adiponectin Dynamics and Systemic Infflamatory Response After Major Colorectal Surgery

Overview

Surgical stress after major abdominal surgery in perioperative period causes neuroendocrine, metabolic and imunologic changes in organism with production of proinfflamatory citokines and results with appearance of systemic infflammmatory response syndrome (SIRS). Dysregulated and overrated SIRS in early postoperative period can lead to complications with additional comorbidities, longer hospital stay and poorer outcome. A low grade chronic infflammatory state in obesity and hypoadiponectinemia can enable the cytokine storm and exaggerated /dysregulated SIRS in obese patients after surgery. Obesity according to this knowledge presents independent risk factor for developing more severe systemic infflamatory response syndrome in early postoperative period after major abdominal surgery. Also, chronic intestinal and gut infflamation is leading theory in oncogenesis of colorectal carcinoma according to recent findings. Many studies find low adiponectin levels in patients with colorectal carcinoma compared to healthy population. Obesity and colorectal cancer have infflamation and low adiponectin level as mutual factor which can be the important key in pathophysiology process of colorectal oncogenesis which are extremly complicated , multifactorial and intertwining. Hypothesis: Lower blood adiponectin levels are associated with higher systemic infflamatory response in patients after major abdominal surgery. Major aim of this study is to investigate correlation between perioperative blood levels of adiponectin and clinical signs of systemic infflamation and blood markers of systemic infflamation in patients after major colorectal surgery.

Gastrointestinal tumors are commonly presented for surgical resections. According to Global Cancer Statistics 2020: GLOBOCAN estimates colorectal carcinoma ranks third in terms of incidence, but second in terms of mortality for overall carcinomas worldwide. At the same time, obesity is a fast growing disease with of pandemic proportions with a current global prevalence of 39% according to the World Health Organisation (WHO). Many patients presented for major abdominal resections of colrectal carcinomas are obese. Obesity is chronic disease with complex pathophisiology. Adipose tissue besides being a storage site is responsible for secretion of various adipokines with imunometabolic role. Adipokines (also called adipocytokines) are cell-signaling molecules (cytokines) produced by the adipose tissue that play many functional roles in energy/metabolic status of the body, and inflammation. Among adipokines, adiponectin is predominantly antiinfflamatory adipokine which inhibits production of infflammatory citokines (IL-6) and is decreased in obesity. Adipocyte dysfunction in obesity with altered adipokines release results in chronic low-grade inflammatory state. Obesity is also well known risk factor for colorectal carcinoma in which oncogenesis adiponectin may be the important key according to recent findings. Surgical stress after major colorectal surgery in perioperative period causes neuroendocrine, metabolic and imunologic changes in organism with production of proinfflamatory citokines and results with appearance of systemic infflammmatory response syndrome (SIRS). Dysregulated and overrated SIRS in early postoperative period can lead to complications with additional comorbidities, longer hospital stay and poorer outcome. A low grade chronic infflammatory state in obesity and colorectal carcinoma associated with potential hypoadiponectinemia can enable the cytokine storm and exaggerated /dysregulated SIRS in these patients after surgery. Due to this knowledge, it is logical to presume that adiponectin levels in perioperative period are associated with the intensity of systemic infflamatory response after major colorectal surgery. Hypothesis: Perioperative blood adiponectin levels are associated with higher intensity of systemic infflamatory response in patients after major colorectal surgery. Aim of this study is to: 1. Measure and investigate correlation between perioperative blood adiponectin levels and appearance and intensity of systemic infflamatory response in patients after major colorectal surgery. 2. Investigate correlation between perioperative blood adiponectin levels, SIRS and postoperative complications, days of ICU and lenght of hospital stay in patients presenting for major colrectal surgery. Research plan: After ethical approval and written informed consent, demographic, antropometric and comorbidities data will be taken from all patients included in study. BMI, waist circumference and ultrasound measurments of abdominal fat thickness ( superficial and visceral abdominal fat thickness) will be taken preoperatively. Blood collections for determining adiponectin levels, IL-6, Complete Blood Count with Differential Blood Count, lactats in arterial blood, C-reactive protein(CRP), procalcitonin(PCT), albumins (ALB), neutrophil/lymphocite ratio (NLR), platelet/lymphocyte ratio (PLR), CRP/ALB ratio, Systemic Immune-Inflammation Index (SII), Systemic inflammation response index (SIRI) will be taken before surgery (1), 24 hours after surgery (2) and 72 hours after surgery (3). All patients will bi given the same technique of balanced general endotracheal anesthesia with the same drugs and the same postoperative multimodal analgesia regimen. Appearance of SIRS in first 72 hours postoperative period will be detected and documented according to standardized major clinical SIRS criteria. Complications in early postoperative period during hospitalisation will be including: surgical operation site related according to standardized Clavien-Dindo classification: anastomotic dehiscence, wound/local infection, postoperative bleeding, reoperation and systemic complications: sepsis, pneumonia, noncardiac respiratory failure, (need for noninvasive oxygen therapy), prolonged mechanical ventilation \>24 hours postoperative, reintubation, repeated mechanical ventilation, cardiovascular complications: atrial fibrillation, congestive heart failure, myocardial infarction, acute kidney injury/failure, postoperative delirium presence. After surgery, histological tumor grade, pathohistological tumor staging ( 8th edition of the American Joint Committee on Cancer (AJCC) staging) and tumor localisation ( colon/rectum) will be documented. Length of ICU and overall hospital stay with outcome of surviving or death after discharge from hospital will be documented. Significance/Expected scientific contribution: Understanding of the underlying pathophysiological mechanisms which contributes to the appearance and severity of SIRS with possible complications in early postoperative period is important for developing more predictive diagnostics and possible treatment options for improvements in outcome especially in major surgical procedures. The adipocytokines have important role in many aspects of inflammation and immunity. This study can help in better understanding the infflamatory role od adiponectin in pathophysiology of SIRS after major colorectal surgery.