Autoimmune pancreatitis (AIP) has been characterized by unique clinical imaging, immunological findings, and the effectiveness of steroid therapy. A set of clinicopathological criteria for AIP was proposed by the Japan Pancreatic Society in 2002, and AIP has come to be widely recognized among general digestive clinicians. However, the indication of steroid therapy for AIP is still not well established, and furthermore the therapeutic doses and method of administration of steroid therapy is also unclear. Recently, an epidemiological survey of all the treatments used for AIP in Japan was conducted by the Research Committee of Intractable Pancreatic Diseases, and their report "Consensus for a Treatment of Autoimmune Pancreatitis" was produced. In a comparison of the results of steroid therapy and nonsteroid therapy for AIP in relation to the rate of complete remission, the recurrence rate, and the period needed to guarantee complete remission, it was thought that the administration of a steroid should be a standard therapy for AIP. However, if the diagnosis of AIP is still uncertain, steroid therapy should be given with caution. In addition, even when AIP still appears to be possible after a course of steroid therapy, a re-evaluation should be carried out taking pancreatic carcinoma into consideration. An initial steroid dose of 30-40 mg per day is recommended. With continuous and careful observations of the clinical manifestations, laboratory data, and imaging findings after administration of the initial dose of steroid for 2-4 weeks, the quantity of steroid can be reduced gradually to a maintenance dose in 2-3 months, and then reduced to 2.5-5 mg per day after remission. The recommended period of maintenance treatment is still unclear, but the administration of the steroid could be stopped after a period of about 6-12 months of treatment, although the patient should be monitored for clinical manifestations of improvement. In addition, the patient's progress should be followed taking recurrence into consideration. In order to evaluate the effectiveness of steroid therapy, follow-up observations should include biochemical examinations of blood findings such as serum gamma-globulin, IgG, and IgG 4, imaging findings, and clinical manifestations such as jaundice and abdominal discomfort.

Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC þ CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-a (TNF-a) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen a1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-a production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen a1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.

These results suggest that this experimental model of pancreatic fibrosis induced by DBTC in rats was useful as a chronic pancreatitis model and that MCP-1 may play an important role in the development of pancreatic fibrosis.

Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 mg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, a-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

A case of solid pancreatic hamartoma in a 58-year-old Japanese woman is presented. She had no symptoms, and a pancreatic mass was incidentally found on screening ultrasonography 4 months before admission. The patient was not alcoholic and had no history of pancreatitis. Physical examination and laboratory data were unremarkable. Preoperative imaging demonstrated a nodule in the body of the pancreas, measuring 2.0 cm in maximum diameter, which showed marked delayed enhancement during dynamic CT. The patient underwent a distal pancreatectomy under the preoperative diagnosis of pancreatic endocrine tumor and had an uneventful postoperative course. A well-demarcated solid nodule, 1.9 cm in diameter, was evident in the body of the pancreas. Microscopically, the lesion was composed of non-neoplastic, disarranged acinar cells and ducts embedded in a sclerotic stroma with elongated spindle cells, lacking discrete islets. The stromal spindle cells were immunoreactive for CD34 and CD117. The histological diagnosis was solid hamartoma of the pancreas. There was no recurrence 5 months after surgery. Herein is reported a case of solid hamartoma of the pancreas and review of the literature. A search through the literature found only two cases of solid hamartoma of the pancreas, among the 14 cases previously reported as pancreatic hamartoma.