Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell–to–α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response to insulin resistance in the absence of overt diabetes.

Background Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular “challenge” for the biliary surgeon. The disease can mimic cancer of the gallbladder, causing considerable diagnostic difficulties. Furthermore, it increases the risk of intraoperative biliary injury during cholecystectomy. The aim of this study is to point out some particular aspects of diagnosis and treatment of this condition. Methods The clinical records of patients with Mirizzi syndrome, treated in the last five years, were reviewed. Clinical data, cholangiograms, preoperative diagnosis, operative procedures, and early and late results were examined. Results Eighteen consecutive patients were treated in the last five years. Presenting symptoms were jaundice, pain, and cholangitis. Preoperative diagnosis of Mirizzi syndrome was achieved in 11 patients, while 6 had a diagnosis of gallbladder cancer and 1 of Klatskin tumor. Seventeen patients underwent surgery, including cholecystectomy in 8 cases, bile duct repair over T-tube in 3 cases, and hepaticojejunostomy in 4 cases. Two cases (11.1%) of gallbladder cancer associated with the Mirizzi syndrome were incidentally found: a patient underwent right hepatectomy and another patient was unresectable. The overall morbidity rate was 16.6%. There was no postoperative mortality. An ERCP with stent insertion was required in three cases after surgery. Sixteen patients were asymptomatic at a mean distance of 24 months (range: 6-48) after surgery. Conclusions Mirizzi syndrome requires being treated by an experienced biliary surgeon after a careful assessment of the local situation and anatomy. The preoperative placement of a stent via ERCP can simplify the surgical procedure.

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Liver resection may represent the only hope of cure for patients with intrahepatic cholangiocarcinoma (IHC) but long-term results are still far from satisfactory and the impact of prognostic factors is still controversial. Fifty-five patients underwent hepatectomy for IHC between 1997 and 2008 in our unit. Features of the patients and the tumors, operations, postoperative and long-term results were retrospectively assessed. Twenty-one patients had HBV/HCV infection, four had congenital biliary dilatation. Thirty-two patients had increased CA 19-9; 12 had multiple (≥ 4) tumors. Operations included 43 major resections, with 9 resections of biliary confluence, 40 regional lymphadenectomies. Operative mortality and morbidity were 0 and 27.3%, respectively. There were 44 R0-resections (80.0%). Lymphadenectomy yielded lymph node metastases in 14 cases (14/40; 35.0%). Five-year overall and disease-free survival rates were 30.2 and 27.5%, respectively. At multivariate analysis the strongest poor prognostic factor for overall survival was tumor stage. This factor, with multiplicity of lesions (≥ 4) and tumor grading > 2, was significant predictor of recurrence. CA19-9 > 100 IU/mL and tumor grading > 2 were found to be significantly related with early multinodular hepatic recurrence. Patients with lymph node metastases had significantly lower overall and disease-free survival but patients who underwent lymph node dissection with negative lymph nodes at final pathology showed significantly higher 5-year disease-free survival than patients who did not underwent lymphadenectomy. In conclusion, these results support the role of hepatectomy with regional lymphadenectomy as the best available treatment for IHC. Prognosis after liver resection correlates with clinical stage and multiplicity of lesions.