NETosis in Surgery: Pathophysiology, Prevention, and Treatment.

OBJECTIVE: To provide surgeons with an understanding of the latest research on NETosis, including the pathophysiology and treatment of conditions involving neutrophil extracellular traps (NETs) in the care of surgical patients. BACKGROUND: A novel function of neutrophils, the formation of NETs, was described in 2004. Neutrophils form mesh-like structures of extruded decondensed chromatin, comprising DNA and histones decorated with bactericidal proteins. These NETs exert antimicrobial action by trapping microorganisms and preventing their wider dissemination through the body. RESULTS: A narrative review of the existing literature describing NETosis was conducted, including NET pathophysiology, conditions related to NET formation, and treatments relevant to surgeons. CONCLUSIONS: In addition to its canonical antimicrobial function, NETosis can exacerbate inflammation, resulting in tissue damage and contributing to numerous diseases. NETs promote gallstone formation and acute pancreatitis, impair wound healing in the early postoperative period and in chronic wounds, and facilitate intravascular coagulation, cancer growth, and metastasis. Agents that target NET formation or removal have shown promising efficacy in treating these conditions, although large clinical trials are required to confirm these benefits.

Molecular Mechanisms of Western Diet-Induced Obesity and Obesity-Related Carcinogenesis-A Narrative Review.

The present study aims to provide a narrative review of the molecular mechanisms of Western diet-induced obesity and obesity-related carcinogenesis. A literature search of the Cochrane Library, Embase and Pubmed databases, Google Scholar and the grey literature was conducted. Most of the molecular mechanisms that induce obesity are also involved in the twelve Hallmarks of Cancer, with the fundamental process being the consumption of a highly processed, energy-dense diet and the deposition of fat in white adipose tissue and the liver. The generation of crown-like structures, with macrophages surrounding senescent or necrotic adipocytes or hepatocytes, leads to a perpetual state of chronic inflammation, oxidative stress, hyperinsulinaemia, aromatase activity, activation of oncogenic pathways and loss of normal homeostasis. Metabolic reprogramming, epithelial mesenchymal transition, HIF-1α signalling, angiogenesis and loss of normal host immune-surveillance are particularly important. Obesity-associated carcinogenesis is closely related to metabolic syndrome, hypoxia, visceral adipose tissue dysfunction, oestrogen synthesis and detrimental cytokine, adipokine and exosomal miRNA release. This is particularly important in the pathogenesis of oestrogen-sensitive cancers, including breast, endometrial, ovarian and thyroid cancer, but also 'non-hormonal' obesity-associated cancers such as cardio-oesophageal, colorectal, renal, pancreatic, gallbladder and hepatocellular adenocarcinoma. Effective weight loss interventions may improve the future incidence of overall and obesity-associated cancer.

Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk.

The study aimed to perform a systematic review and meta-analysis of the evidence for the prevention of future cancers following bariatric surgery. A systematic literature search of the Cochrane Library, Embase, Scopus, Web of Science and PubMed databases (2007-2023), Google Scholar and grey literature was conducted. A meta-analysis was performed using the inverse variance method and random effects model. Thirty-two studies involving patients with obesity who received bariatric surgery and control patients who were managed with conventional treatment were included. The meta-analysis suggested bariatric surgery was associated with a reduced overall incidence of cancer (RR 0.62, 95% CI 0.46-0.84, p < 0.002), obesity-related cancer (RR 0.59, 95% CI 0.39-0.90, p = 0.01) and cancer-associated mortality (RR 0.51, 95% CI 0.42-0.62, p < 0.00001). In specific cancers, bariatric surgery was associated with reduction in the future incidence of hepatocellular carcinoma (RR 0.35, 95% CI 0.22-0.55, p < 0.00001), colorectal cancer (RR 0.63, CI 0.50-0.81, p = 0.0002), pancreatic cancer (RR 0.52, 95% CI 0.29-0.93, p = 0.03) and gallbladder cancer (RR 0.41, 95% CI 0.18-0.96, p = 0.04), as well as female specific cancers, including breast cancer (RR 0.56, 95% CI 0.44-0.71, p < 0.00001), endometrial cancer (RR 0.38, 95% CI 0.26-0.55, p < 0.00001) and ovarian cancer (RR 0.45, 95% CI 0.31-0.64, p < 0.0001). There was no significant reduction in the incidence of oesophageal, gastric, thyroid, kidney, prostate cancer or multiple myeloma after bariatric surgery as compared to patients with morbid obesity who did not have bariatric surgery. Obesity-associated carcinogenesis is closely related to metabolic syndrome; visceral adipose dysfunction; aromatase activity and detrimental cytokine, adipokine and exosomal miRNA release. Bariatric surgery results in long-term weight loss in morbidly obese patients and improves metabolic syndrome. Bariatric surgery may decrease future overall cancer incidence and mortality, including the incidence of seven obesity-related cancers.