Junichi Niikawa

A case of autoimmune pancreatitis responding to steroid therapy

We report a case of autoimmune pancreatitis without obvious evidence of autoimmunological participation, which responded well to steroid treatment and provided histologic and radiographic evidence for this improvement. A 68-year-old woman presented abdominal fullness, diffuse pancreatic swelling on abdominal computed tomography and ultrasonography, and diffuse narrowing of the main pancreatic duct on endoscopic retrograde pancreatography. Transgastric aspiration needle biopsy of the body of the pancreas performed under endoscopic ultrasonography showed severe atrophy of acinar cells, infiltration of T lymphocytes. She was diagnosed as having autoimmune pancreatitis without obvious evidence of autoimmunological participation. Administration of 30 mg/day of predonisolone was started. Computed tomography showed marked improvement of the diffuse swelling of the pancreas, and endoscopic retrograde pancreatograpy showed amelioration of the narrowing of the main pancreatic duct after the start of treatment. Pancreatic tissue obtained by needle biopsy after the start of treatment with predonisolone revealed marked histologic improvement, including amelioration of the fibrosis, and infiltration of inflammatory lymphocytes, and a substantial increase in the number of pancreatic acinar cells. The present report is the first to demonstrate histologic recovery of autoimmune pancreatitis after steroid therapy.

Significance of measurement of high-sensitivity C-reactive protein in acute pancreatitis

Background: Determination of the severity of acute pancreatitis is difficult in the early phase after onset, and we often encounter difficulties in making decisions to initiate intensive care during the early phase. Therefore, there is real need for a simple and inexpensive method that can precisely evaluate the severity of acute pancreatitis. Methods: In the present study, we measured serum C-reactive protein (CRP) levels in 20 patients with acute pancreatitis, using a high-sensitivity CRP (hs-CRP) assay method. Results: CRP levels were as low as 1.0, 0.4, and 0.3 mg/dl in cases 2, 3, and 9, respectively, with severe acute pancreatitis. These three patients were hospitalized within 24 h after the onset of pancreatitis. Cases 2, 3, and 9 showed high hs-CRP levels, of 209 000, 68 600, and 154 000 ng/ml, respectively, and their interleukin (IL)-6 levels were above 500 pg/ml. The mean hs-CRP level was 222 760 ± 32 197 ng/ml in patients with severe acute pancreatitis and 22 798 ± 8216 ng/ml in patients with mild to moderate pancreatitis, with a significantly higher level in the severe cases. Cases 14, 16, and 20, with mild to moderate pancreatitis, had hs-CRP levels of 83 400, 1800, and 55 400 ng/ml, respectively. Conclusions: Measurement of hs-CRP levels is a simple and inexpensive method. The hs-CRP levels were found to significantly increase in the early phase of severe acute pancreatitis, suggesting that hs-CRP could possibly serve as an early indicator of the progression of acute pancreatitis into a serious state.

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

Background. We examined the effects of cholecystokinin (CCK) on the development of ethionine-induced pancreatitis and pancreatic recovery. We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model lacking pancreatic CCK-A receptor gene expression. Methods. Ethionine-induced pancreatitis was induced in the 7-week-old male OLETF rats and in a control group that does not lack the pancreatic CCK-A receptor, Long-Evans Tokushima Otsuka (LETO) rats. The two groups were maintained on a low-protein diet for 11 days. During the last 4 days of the low-protein diet, dl-ethionine 20 mg/100 g body weight was administered intraperitoneally once daily. Histologic and biochemical examinations of the pancreas were performed, and plasma CCK concentrations were measured on days 1, 4, and 7 after the last ethionine administration. Results. Pancreatic histologic scores for inflammation, hemorrhage, and necrosis in the LETO and OLETF rats were highest on days 1 and 4, respectively. Pancreatic weight, DNA content, and protein level per DNA content in both groups decreased during the low-protein diet, and recovery signs were delayed in the OLETF rats. The highest plasma CCK concentrations in the LETO and OLETF rats were reached on days 1 and 4, respectively. Conclusions. Ethionine-induced pancreatitis developed in the OLETF rats, and their pancreatic regeneration was delayed in comparison to that in the LETO rats. Our results suggested that CCK plays an important role in the development of pancreatitis as well as in the pancreatic repair process.

Involvement of calmodulin and protein kinase C in cholecystokinin release by bombesin from STC-1 cells.

The mouse intestinal neuroendocrine tumor cell line STC-1 secretes cholecystokinin (CCK) and other hormones. We investigated the role of Ca2+, calmodulin (CaM), and protein kinase C (PKC) in the regulation of CCK release from STC-1 cells. Phorbol 12-myristate 13-acetate (TPA) significantly stimulated CCK release. Staurosporine significantly inhibited CCK release from STC-1 cells stimulated by TPA in a dose-dependent manner. The absence of extracellular calcium completely inhibited CCK release from TPA-stimulated STC-1 cells. Neurotensin did not stimulate CCK release from these cells. W-7, a CaM antagonist, reduced CCK release from STC-1 cells stimulated by bombesin in a dose-dependent manner. These findings suggest that CaM and PKC play an important role in the regulation of CCK release from STC-1 cells stimulated by bombesin.

Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration

Background: Tissue destruction arising from neutrophil infiltration of the pancreas and other organs in acute pancreatitis is supposed to be suppressed by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in rats. Methods: Rats fed with a low protein diet for 11 days received daily intraperitoneal administration of DL-ethionine (20 mg/100 g) for the last 4 days of the diet. To evaluate the therapeutic effect on ethionine-induced pancreatitis, IS-741 (10 mg/kg s.c.) was administered every 8 h beginning after the second ethionine injection (IS group). An equal volume of saline was used for control rats as alternative to IS-741 (control group). The rats were killed 1, 3, 5, and 7 days after the last injection of ethionine. Blood was collected to measure concentrations of the inflammatory cytokine, interleukin-8. Histologic and biochemical examinations of the pancreas were performed. The pancreatic weight, DNA content, and protein levels were determined. The pancreas was histologically examined. Results: Pancreatic tissue in the control group showed marked infiltration of inflammatory cells, and acinar cell necrosis was widespread 1 day after the last injection of ethionine (day 1). The severity of acute pancreatitis was alleviated in rats treated with IS-741 (IS group). Pancreatic wet weight and DNA content in the IS group were higher than those in the control group on day 1. Pancreatic protein level per DNA in the IS group was higher than that in the control group on day 7. The plasma interleukin-8 level in the control group was higher than that in the IS group on day 5. Conclusions: Therapeutic administration of IS-741 ameliorated ethionine-induced acute pancreatitis in rats, and IS-741 could be a useful drug to treat patients with severe acute pancreatitis.