Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.

BACKGROUND: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity. METHODS: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology. RESULTS: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis. CONCLUSIONS: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications.

Severe acute pancreatitis causes a high incidence of mortality due to the systemic inflammatory response syndrome leading to multiple organ failure. At present, there is no treatment against severe acute pancreatitis, other than supportive critical care. The relationship between pancreatic injury and the uncontrolled systemic response is not completely understood. Nevertheless, experimental and clinical evidences have shown that pro-inflammatory cytokines and oxidative stress are critically involved in the development of local and systemic complications associated with severe acute pancreatitis. Serum levels of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, increase during the course of acute pancreatitis and they appear to be the driving force for the initiation and propagation of the systemic response. Accordingly, pretreatment with an antibody against TNF-alpha or blockade of TNF-alpha production with pentoxifylline ameliorates experimental acute pancreatitis. In addition, serum IL-6 and IL-8 levels appear to be correlated with severity of pancreatic inflammation. The role of oxidative stress in acute pancreatitis has been evidenced indirectly by beneficial effects of antioxidants as well as directly by pancreatic glutathione depletion and increased lipid peroxidation. Furthermore, circulating xanthine oxidase released by the damaged pancreas acts as a source of systemic oxidative stress contributing to lung inflammation. In conclusion, pancreatic injury seems to trigger at least two different pathways, i.e. pro-inflammatory cytokines and oxidative stress, both involved in the systemic effects of acute pancreatitis. Elucidation of these mechanisms and their interactions is critical to develop a treatment based on the pathophysiology of acute pancreatitis.

Bile duct injury during laparoscopic cholecystectomy: myth or reality of the learning curve?

BACKGROUND: Bile duct injury (BDI) is a severe complication of laparoscopic cholecystectomy (LC) that is probably related to the effects of the learning curve. The aim of this prospective, institutional, and longitudinal study is to compare the incidence of BDI during LC in relation to the progressive experience of surgeons. METHODS: A total of 784 LC were examined during a 6-year period. They were divided into the following three consecutive groups: group A (1993-94), group B (1995-96), and group C (1997-98). Incidence and type of BDI, experience of the surgeon, intra- or postoperative diagnosis, treatment performed to repair the injury, and early and late morbidity and mortality were evaluated. RESULTS: The overall incidence of BDI was 1.4%. There were three cases of transection of the common bile duct, four partial lesions of the bile duct, and four cystic leakages. The number of BDI was maintained over the three different time periods; there were no statistical differences in the proportion of injuries among groups. Most BDI were incurred by experienced surgeons. In all, 36% of BDI were recognized intraoperatively. Hepaticojejunostomy, direct suture over a T-tube, and closure of the cystic stump were done to repair BDI. There was no additional morbidity or mortality in the patients with BDI. CONCLUSIONS: No relation was found between the experience of the surgeon and the number of BDI over the different periods of time. Therefore, BDI during LC cannot be attributed solely to the learning curve.