Diagnosis and surgical management of gallbladder cancer: a review.

Gallbladder cancer is one of the most lethal carcinomas and continues to pose many challenges for surgeons. Identifiable risk factors for carcinoma of the gallbladder include cholelithiasis, an anomalous pancreaticobiliary junction, and focal mucosal microcalcifications. Adenocarcinoma is the primary histologic type in most patients and the tumor is frequently associated with Kras and p53 mutations. Radiologic and endoscopic advances in endoscopic ultrasonography and magnetic resonance cholangiopancreatogram, plus helical computed tomography, have enhanced preoperative staging. Surgical options include cholecystectomy for disease limited to the mucosa (Tis/T1) or a radical cholecystectomy (subsegmental resection of segments IVB and V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without signs of distant metastasis (T2-4/N0-N2). Some surgeons have advocated more radical hepatic resection including extended right hepatectomy or central bisegmentectomy plus caudate lobectomy. Japanese surgeons have reported studies that included patients having a pancreaticoduodenectomy to improve distal ductal margins and lymphadenectomy for T3 and T4 cancers. These patients have a lower rate of local recurrence but no survival advantage. Options for adjuvant therapy remain limited. Radiation therapy with fluorouracil radiosensitization is the most commonly used postoperative treatments. Current trials are investigating the role of capecitabine, oxaliplatin, and bevacizumab in the management of gallbladder carcinoma.

Liver I/R injury is improved by the arginase inhibitor, N(omega)-hydroxy-nor-L-arginine (nor-NOHA).

Liver ischemia-reperfusion (I/R) injury is associated with profound arginine depletion due to arginase release from injured hepatocytes. The purpose of this study was to determine whether arginase inhibition with N(omega)-hydroxy-nor-l-arginine (nor-NOHA) would increase circulating arginine levels and decrease hepatic damage during liver I/R injury. The effects of nor-NOHA were initially tested in normal animals to determine in vivo toxicity. In the second series of experiments, orthotopic syngeneic liver transplantation (OLT) was performed after 18 h of cold ischemia time in Lewis rats. Animals were given nor-NOHA (100 mg/kg) or saline before and after graft reperfusion. In normal animals treated with nor-NOHA, there were no histopathological changes to organs, liver enzymes, serum creatinine, or body weight. In the OLT model, animals treated with saline exhibited markedly elevated serum transaminases and circulating arginase protein levels. Nor-NOHA administration blunted the increase in serum arginase activity by 80% and preserved serum arginine levels at 3 h after OLT. Nor-NOHA treatment reduced post-OLT serum liver enzyme release by 50%. Liver histology (degree of necrosis) in nor-NOHA-treated animals was markedly improved compared with the saline-treated group. Furthermore, use of the arginase inhibitor nor-NOHA did not influence polyamine synthesis owing to the decrease in ornithine levels. Arginase blockade represents a potentially novel strategy to combat hepatic I/R injury associated with liver transplantation.