The findings show that NAC is a feasible and promising treatment option for LARC (This study is registered with UMIN-CTR, UMIN000005654).

Metallothioneins are a family of intracellular metalloproteins that have been thought to be involved in anticancer drug resistance. However, the role of metallothioneins in pancreatic cancer has not been investigated in detail. The immunohistochemical localization of metallothionein was examined in normal human adult pancreas tissue and in 75 pancreatic duct cell carcinomas, using monoclonal anti-metallothionein antibody. Furthermore, in vitro studies on the sensitivity of pancreatic cancer to cisplatin were performed in 10 cases of pancreatic carcinoma. Metallothionein staining was weakly positive in the acinar and islet cells and intralobular ducts but was negative in the large pancreatic ducts. In pancreatic carcinomas, metallothionein staining was diffusely positive in 6 (8%), focally positive in 25 (33%) and negative in 44 (59%) of the 75 pancreatic carcinomas. The expression of metallothioneins in pancreatic tumors was related to metastasis, poor prognosis and poor histological grading (poorer glandular differentiation and nuclear anaplasia). The in vitro study of tumor sensitivity to cisplatin showed no significant correlation between metallothionein expression and resistance to cisplatin. Metallothionein-positive pancreatic carcinoma will be potentially highly malignant or acquire an enhanced ability to produce metallothioneins as the malignant potential increases. The expression of metallothionein could be a prognostic indicator in pancreatic carcinomas.

Transanal tube placement is effective for decreasing the incidence of symptomatic AL after LAR.

The role of free radicals in the development of cerulein-induced pancreatitis was evaluated by measuring the activity of the endogenous scavengers, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx), as indicators of the defense system, and the level of lipid peroxide (LPO) in the pancreas, as an indicator of the offense system. Acute pancreatitis was induced by 5 hourly intraperitoneal administrations of cerulein (50 μg/kg body weight), in 0.9% NaCl, to mice. The presence of acute pancreatitis was confirmed by changes in serum amylase levels and in typical microscopical features. Regarding the changes in the levels of endogenous scavengers, the SOD level was decreased significantly from a basal level of 52.6 ± 3.94 to 43.1 ± 2.79 mU/μg DNA at 6 h (p < 0.01) to 38.8 ± 5.18 mU/μg DNA at 9 h (p < 0.05) and to 31.7 ± 3.10 mU/μg DNA at 12 h (p < 0.01) after the first intraperitoneal cerulein injection. The CAT level also decreased significantly from a basal level of 7.80 ± 0.27 to 5.86 ± 0.46 mU/μg DNA at 9 h (p < 0.01) and to 4.52 ± 0.21 mU/μg DNA at 12 h (p < 0.01). GSHpx increased from a basal level of 6.80 ± 0.43 to 7.58 ± 0.50 mU/μg DNA at 9 h and to 10.2 ± 0.52 mU/μg DNA at 12 h after the first intraperitoneal cerulein injection. The LPO level increased from a basal level of 1.11 ± 0.48 to 7.22 ± 1.75 nmol/ml at 3.5 h(p < 0.05), 5.40 ± 1.50 nmol/ml at 6 h(p < 0.05), 3.86 ± 1.07 nmol/ml at 9 h (p < 0.05) and 3.18 ± 1.18 nmol/ml at 12 h (p < 0.01) after the first intraperitoneal cerulein injection. These results indicate that tissue imbalances of the offense system, indicated by changes in the level of LPO, and of the defense system, indicated by changes in the levels of SOD and CAT, might result in the development of tissue damage induced by oxygen-derived free radicals.

Ischemia has been considered to play a role in the development of acute pancreatitis. The aim of this study was to investigate the effect of ischemia, caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by the intravenous infusion of a supramaximally stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock was induced by the removal of blood until the mean arterial blood pressure reached 35 mm Hg. This level was maintained for 30 min, after which time all the blood was reinfused. Hemorrhagic shock alone induced no morphological change in the pancreas. However, after the induction of hemorrhagic shock in animals treated with cerulein, hemorrhage and parenchymal necrosis were frequently observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas none of the rats in the cerulein or shock group died during this experiment. Cathepsin B activity in the pancreas of the cerulein plus shock group was significantly higher than in the other groups at 48 hr. These results suggest that ischemia may be a contributing factor in the pathogenesis of acute pancreatitis.