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The patient was a 58-year-old male with symptomatic alcoholic chronic pancreatitis. Since a 10 mm calculus was observed in the pancreatic body and abdominal pain occurred due to congestion of pancreatic juice, endoscopic retrograde cholangiopancreatography was conducted for assessment of the pancreatic duct and treatment of pancreatic calculus. Pancreatogram was slightly and insufficiently obtained by injecting the contrast media via the common channel of the duodenal main papilla. We tried to cannulate selectively into the pancreatic duct for a clear image. However, the selective cannulation of the pancreatic duct was difficult because of instability of the papilla. On the other hand, selective cannulation of the bile duct was relatively easily achieved. Therefore, after the imaging of the bile duct, a guidewire was retained in the bile duct to immobilize the duodenal papilla and cannulation of the pancreatic duct was attempted. As a result, selective pancreatic duct cannulation became possible. It is considered that the bile duct guidewire-indwelling method may serve as one of the useful techniques for cases whose selective pancreatic duct cannulation is difficult ("selective pancreatic duct difficult cannulation case").

Background/aims: Transpancreatic precut papillotomy (TPPP) is considered as an effective method in patients with difficulty in selective biliary cannulation. However, the use of placing a pancreatic duct stent as a measure against post-ERCP pancreatitis has not been clarified. Here we examine the methods of implementing TPPP safely., Methodology: TPPP was conducted on patients with difficulty in selective biliary cannulation. The incidence of pancreatitis was compared between group P(+) in which a spontaneous dislodgement type pancreatic duct stent was placed and group P(-) without a duct stent., Results: The success rate of biliary cannulation was 83.3% at the first ERCP and finally 93.9%. Post-ERCP pancreatitis was observed in 9.09% of patients. The success rate of placement of pancreatic duct stent in the P(+) group was 100%. The incidence of pancreatitis in the P(+) group was 4.1% and the mean post-ERCP amylase level was 340.071 ±420.035IU/L. The incidence of pancreatitis in the P(-) group was 23.5% and the mean post-ERCP amylase level was 661.250±772.285IU/L. The incidence of pancreatitis and the mean post-ERCP amylase level were significantly lower in the P(+) group (p<0.05)., Conclusions: In the patients with difficulty in selective biliary cannulation, TPPP is a useful technique for biliary cannulation. The placement of a spontaneous dislodgement type pancreatic duct stent after TPPP may be useful for prevention of post-ERCP pancreatitis.

Background/aims: To examine the utility of placement of pancreatic duct spontaneous dislodgement stents for prevention of post-ERCP pancreatitis in patients with difficulty in selective biliary cannulation., Methodology: The incidence of pancreatitis was compared between the group with P(+) pancreatic duct spontaneous dislodgement stent placed for prevention of post-ERCP pancreatitis and the group without P(-) in patients with difficulty in selective biliary cannulation., Results: The final success rate of selective biliary cannulation was 94.45%. Post-ERCP pancreatitis was observed at 7.07%. The success rate of placement of pancreatic duct stent in the P(+) group was 99.0%. The incidence of pancreatitis in 99 patients in the P(+) group was 3.0%, that of abdominal pain was 3.0%, that of hyperamylasemia was 16.2%, and the mean post-ERCP amylase level was 353.031 +/- 520.792 IU/L. The incidence of pancreatitis in the P(-) group was 11.1%, that of abdominal pain was 20.2%, that of hyperamylasemia was 33.3%, and the mean post-ERCP amylase level was 541.204 +/- 771.843 IU/L. Comparing between the P(+) group and P(-) group, the incidence of pancreatitis, that of abdominal pain, that of hyperamylasemia and the mean post-ERCP amylase level were significantly decreased in the P(+) group (p<0.05)., Conclusion: Placement of pancreatic duct spontaneous dislodgement stent in patients with difficulty in selective biliary cannulation could be useful for prevention of post-ERCP pancreatitis.

Background/aims: Pancreatic duct guidewire-indwelling method (P-GW) is effective when selective biliary cannulation (SBC) has failed, but neither its true success rate nor a salvage technique have been established. In this study, we examined the usefulness of pre-cut papillotomy employing a pancreatic duct guidewire as the salvage treatment after unsuccessful SBC under P-GW., Methodology: P-GW was conducted in 55 patients. When cannulation under P-GW was unsuccessful, pre-cut papillotomy was performed. Then, if SBC after trial was still unsuccessful, ERCP was tried again at a later date. The incidence of pancreatitis following ERCP in patients with difficult SBC, with and without pancreatic duct stenting was determined., Results: P-GW resulted in successful SBC in 63.6% of patients. For the 20 patients in which SBC failed pre-cut papillotomy using the pancreatic duct guidewire was performed. Transpancreatic pre-cut papillotomy was performed in 17 patients; 3 patients underwent needle-knife pre-cut papillotomy. SBC was successful at first attempt in 89.1% and eventually in 96.4% of patients. Post-ERCP pancreatitis occurred in 7.3%, broken down into 0% for those with pancreatic duct stenting (p=0.03) and 16.7% for those without., Conclusions: Pre-cut papillotomy using a pancreatic duct guidewire was useful for patients with unsuccessful SBC with P-GW alone, and the risk for pancreatitis was reduced by pancreatic stenting.

In gastric cancer, several tumor suppressor and tumor-related genes are silenced by aberrant methylation. Previously, we demonstrated that BCL2L10, which belongs to the pro-apoptotic Bcl-2 family, was transcriptionally repressed by promoter hypermethylation and that its overexpression caused apoptosis and growth inhibition of gastric cancer cells. In this study, we investigated the methylation status of BCL2L10 and its expression in 21 gastric cancer tissues and corresponding non-neoplastic mucosae along with the methylation status of p16, RUNX3, and hMLH1 genes by using methylation specific PCR. In addition, we examined the association between the methylation status of each gene and the expression of EZH2, which was associated with DNA methylation of its target genes. As a result, aberrant methylation of BCL2L10 was detected in 38% of gastric cancer and in 24% of corresponding non-neoplastic mucosae and correlated with low expression of BCL2L10. Methylation of p16, RUNX3, and hMLH1 was found in gastric cancer and in corresponding non-neoplastic mucosae at almost similar frequencies as previous reports. Expression of EZH2 was detected more frequently in tumors (48%) as compared to corresponding non-neoplastic mucosae (10%) (p=0.006), however, no significant difference was found between expression of EZH2 and the methylation frequency of each gene. In conclusion, our data suggest that silencing of BCL2L10 by aberrant methylation is a common feature in gastric cancer and its inactivation may be involved in the early steps of gastric carcinogenesis.

A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.

To determine the clinical significance of gene promoter methylation in esophageal squamous cell carcinoma (ESCC), we examined the promoter methylation status of genes showing elevated expression, as determined by DNA microarray-based transcriptomic analysis, in three ESCC cell lines (TE-1, TE-2, TE-10) after 5-aza-2'-deoxycytidine (DAC) treatment. We observed a high degree of DNA methylation within the promoter regions of three genes, namely cathepsin L2 (CTSL2), normal mucosa of esophagus specific 1 (NMES1), and fatty acid binding protein 5 (FABP5). Overexpression of NMES1 in ESCC cell lines increased cell motility. Down-regulation of NMES1 might play an important role in the cell motility of ESCC or be a potent marker of malignancy.

Background/aims: The aim of this study was to investigate the effects of being overweight on autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) patients., Methodology/results: 44 AIH and 95 PBC patients were enrolled in this study. Body weight and body mass index (BMI) of AIH (57.6 +/- 10.4 kg and 23.8 +/- 2.9 kgm(-2), respectively) were higher than those of PBC (51.6 +/- 7.0 kg and 22.0 +/- 2.6 kgm(-2), respectively) (P < 0.001). The prevalence of overweight patients in AIH was also higher than those in PBC (P < 0.005). Being overweight and having 25 < or = BMI < 30 did not affect the progression of hepatic fibrosis in AIH and PBC. In comparison with the non-overweight with PBC, overweight patients with PBC tended not to be symptomatic, such as having itching or fatigue (P = 0.027)., Conclusions: Clinicians should be aware that not only non-alcoholic fatty liver disease but also PBC patients might be included among the overweight hepatic disease patients with unknown etiology.

Background/aims: Antiviral therapy such as combination interferon and ribavirin can eradicate hepatitis C virus (HCV) RNA by up to 40-50%. However, many patients still remain non-responders to this treatment for various reasons. The aim of this study was to evaluate the effect of interferon or ribavirin treatment on subgenomic HCV RNA replication in 'non-hepatic' HeLa cells., Methodology: Huh-7 or HeLa cells harboring HCV replicon were constructed by using cellular RNA of Huh-7 harboring HCV replicon RNAs, named as C13-3 cells. We also tested whether interferon or ribavirin can suppress HCV RNA in HeLa cells., Results: Huh-7 or HeLa cells harboring HCV replicon RNAs were constructed by using cellular RNA of C13-3 cells than using in vitro-transcribed RNA. Ribavirin at 1 microg/mL or 10 microg/mL did not suppress colony formation in HeLa cells, but at 100 microg/mL suppression was observed. Interferon-alpha 2b suppressed HCV replication even at 1 U/mL., Conclusions: HeLa cells harboring HCV replicon RNAs also might be useful for the development of antiviral drugs.

Long-term interferon therapy is an alternative therapy for patients with chronic hepatitis C who can not tolerate to the combination of pegylated interferon and ribavirin. In 2005, self-injection of interferon for chronic hepatitis C was covered by public health insurance in Japan making the long-term interferon therapy easier to perform. For the safe performance of self-injection, education about knowledge on various adverse effects of interferon, training for actual performance of self-injection, and close contact between the patients and doctors are indispensable. In this review, we briefly summarized why self-injection is needed and how the training for safe self-injection of interferon should be performed.

Hepatitis E virus (HEV) is the major etiologic agent of enterically transmitted viral hepatitis in many developing countries. Epidemics are primarily waterborne in areas where water supplies are contaminated with HEV of human origin. There is increasing evidence, however, that HEV is also prevalent in very low numbers in non-endemic countries, including Japan. Although the source of HEV in these sporadic cases is unknown, a recently isolated swine virus is the best candidate for causing a zoonotic form of hepatitis E. The virus is serologically cross-reactive with human HEV and genetically very similar, and the human and swine strains seem to be cross-infective. Very recent evidence has also shown that swine HEV, and possibly a deer strain of HEV, may be related to avian HEV and HEV in other hosts and potential reservoirs. We examined the prevalence of anti-HEV IgM and IgG among patients serologically diagnosed with non-A, non-B, non-C acute hepatitis (n = 126) and compared with a matched control group of 76 individuals. Enzyme-linked immunosorbent assay revealed a significant difference in seroprevalence between the two groups for anti-HEV IgM (5.6% versus 0%), whereas there was no difference for anti-HEV IgG (21.4% versus 26.3%). For confirmed cases of anti-HEV IgM we also detected HEV RNA in sera by means of a sensitive polymerase chain reaction (PCR) assay. This study provides evidence of locally acquired hepatitis E in the Chiba area. Therefore, in cases of unexplained acute hepatitis, the diagnosis of hepatitis E should be considered even in the absence of foreign travel.