Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.

A 73-year-old woman was referred to our hospital for persistent liver dysfunction. When the patient was 45 years old, her youngest sister had been diagnosed with Wilson disease (WD). The patient therefore underwent several family screening tests, all of which were unremarkable. She had an annual medical checkup and was diagnosed with liver dysfunction and fatty liver at 68 years old. A liver biopsy and genetic testing were performed, and she was diagnosed with WD; chelation therapy was then initiated. In patients with hepatic disorders and a family history of WD, multiple medical examinations should be conducted, as the development of WD is possible regardless of age.

Rupture of Hepatic Pseudoaneurysm Formed Nine Years after Carbon Ion Radiotherapy for Hepatocellular Carcinoma.

An 83-year-old man with a history of carbon ion radiotherapy for hepatocellular carcinoma nine years ago presented to a primary care hospital with a fever and abdominal pain. He underwent computed tomography, which revealed the rupture of a hepatic pseudoaneurysm close to the fiducial marker for carbon ion radiotherapy and bleeding into the bile duct. He was successfully treated with transcatheter arterial embolization. Thereafter, re-rupture occurred from a site proximal to the first rupture, and this was treated similarly. It is necessary to be alert for not only tumor recurrence but also pseudoaneurysm occurrence after carbon ion radiotherapy.

Malignant transformation of a gastric hyperplastic polyp in a context of Helicobacter pylori-negative autoimmune gastritis: a case report.

BACKGROUND: Gastric foveolar hyperplastic polyps (GFHPs) are common findings in clinical practice. GFHPs commonly arise in a background of chronic atrophic gastritis, including autoimmune gastritis (type A gastritis), and have a potential risk of malignant transformation. CASE PRESENTATION: In 2005, a 55-year-old Japanese woman underwent upper endoscopy at another hospital and was found to have a pedunculated polyp (10 mm in diameter) on the greater curvature of the lower gastric body. On biopsy, the polyp was diagnosed as a GFHP. Nine years later, the polyp had grown to 20 mm in diameter, and the biopsy specimen taken at this time showed tubular adenocarcinoma. On admission to our hospital, the serum Helicobacter Pylori (H. pylori) immunoglobulin G antibody and stool H. pylori antigen were both negative. Anti-gastric parietal cell antibody was positive, as was the anti-intrinsic factor antibody, and the fasting serum gastrin level was markedly increased. In 2014, en bloc resection of the pedunculated polyp was performed by endoscopic submucosal dissection. The final histological diagnosis was adenocarcinoma of the stomach with submucosal and lymphatic invasion. Subsequently, additional radical distal gastrectomy was performed. At the latest follow-up (12 months postoperatively), no recurrence was noted. CONCLUSIONS: We here reported a rare case of malignant transformation of GFHP arising in a context of type A gastritis. To our knowledge, there are no previous reports on malignant transformation of GFHP with submucosal and lymphatic invasion arising in a background of type A gastritis in the English literature. Further, there is currently no effective treatment other than endoscopic or surgical treatment for such cases. Given the potential risk of malignant transformation due to hypergastrinemia, we consider that endoscopic treatment should be considered as a first-line therapy when a malignant growth is suspected.

Hemorrhagic gastric and duodenal ulcers after the Great East Japan Earthquake Disaster.

AIM: To elucidate the characteristics of hemorrhagic gastric/duodenal ulcers in a post-earthquake period within one medical district. METHODS: Hemorrhagic gastric/duodenal ulcers in the Iwate Prefectural Kamaishi Hospital during the 6-mo period after the Great East Japan Earthquake Disaster were reviewed retrospectively. The subjects were 27 patients who visited our hospital with a chief complaint of hematemesis or hemorrhagic stool and were diagnosed as having hemorrhagic gastric/duodenal ulcers by upper gastrointestinal endoscopy during a 6-mo period starting on March 11, 2011. This period was divided into two phases: the acute stress phase, comprising the first month after the earthquake disaster, and the chronic stress phase, from the second through the sixth month. The following items were analyzed according to these phases: age, sex, sites and number of ulcers, peptic ulcer history, status of Helicobacter pylori (H. pylori) infection, intake of non-steroidal anti-inflammatory drugs, and degree of impact of the earthquake disaster. RESULTS: In the acute stress phase from 10 d to 1 mo after the disaster, the number of patients increased rapidly, with a nearly equal male-to-female ratio, and the rate of multiple ulcers was significantly higher than in the previous year (88.9% vs 25%, P < 0.005). In the chronic stress phase starting 1 mo after the earthquake disaster, the number of patients decreased to a level similar to that of the previous year. There were more male patients during this period, and many patients tended to have a solitary ulcer. All patients with duodenal ulcers found in the acute stress phase were negative for serum H. pylori antibodies, and this was significantly different from the previous year's positive rate of 75% (P < 0.05). CONCLUSION: Severe stress caused by an earthquake disaster may have affected the characteristics of hemorrhagic gastric/duodenal ulcers.

[Successful endoscopic transpapillary pancreaticobiliary drainage for omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula].

A 78-year-old man with hepatocellular carcinoma treated by chemoembolization and percutaneous ethanol injection was admitted to our hospital because of acute abdomen. The CT scan showed biliary fistula caused by hepatocellular carcinoma protruding from S3. Endoscopic retrograde cholangiopancreatography showed disruption of an intrahepatic duct and the main pancreatic duct, and contrast agent leaked into the peritoneal cavity from each duct. Omental panniculitis with biliary fistula and pancreatic fistula was diagnosed. The symptoms improved by endoscopic nasobiliary drainage and endoscopic pancreatic stenting. On the 13th day after admission, we added endoscopic nasopancreatic drainage because his abdominal pain had been exacerbated by pancreatic juice leakage. Omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula is extremely rare. Endoscopic transpapillary pancreaticobiliary drainage was effective for omental panniculitis in this case.

Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection.

Hepatitis C virus (HCV), a member of the Flaviviridae family, is a single-stranded positive-sense RNA virus that infects >170 million people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite its ability to block the innate host response in infected hepatocyte cell lines in vitro, HCV induces a strong type 1 interferon (IFN) response in the infected liver. The source of IFN in vivo and how it is induced are currently undefined. Here we report that HCV-infected cells trigger a robust IFN response in plasmacytoid dendritic cells (pDCs) by a mechanism that requires active viral replication, direct cell-cell contact, and Toll-like receptor 7 signaling, and we show that the activated pDC supernatant inhibits HCV infection in an IFN receptor-dependent manner. Importantly, the same events are triggered by HCV subgenomic replicon cells but not by free virus particles, suggesting the existence of a novel cell-cell RNA transfer process whereby HCV-infected cells can activate pDCs to produce IFN without infecting them. These results may explain how HCV induces IFN production in the liver, and they reveal a heretofore unsuspected aspect of the innate host response to viruses that can subvert the classical sensing machinery in the cells they infect, and do not infect or directly activate pDCs.

[A case of tubercular papillitis of Vater].

A 47-year-old man presented with an abnormality of the duodenum detected on a health check endoscopy. Further endoscopy revealed swelling of the papilla of Vater with a whitish exudate and surrounding small nodules, which biopsy revealed to be non-caseating granulomas. Colonoscopy showed typical tubercular lesions in the colon on the right side, so we speculated that the lesions of the papilla of Vater were tubercular. After the administration of anti-tubercular drugs, both the duodenal lesion and the colonic lesions improved. Therefore, the papilla of Vater lesion was diagnosed as tubercular, although such cases are extremely rare.

Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules.

The chimpanzee (Pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (Patr) class I MHC. In the present study we have characterized the peptide binding specificity of several common Patr class I molecules. Using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding motifs have been derived for Patr A*0101, A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides using position 2 and the C terminus as main anchor contacts. On the other hand, each Patr molecule is associated with a unique binding specificity, and the range of specificities is similar to that seen amongst HLA alleles. A high degree of cross-reactivity was noted between Patr A*0701 and Patr A*0901, suggesting the existence of a Patr-specific supertype. Consistent with previous studies suggesting that some cross-reactivity may exist between HLA and Patr alleles, Patr A*0901 was found to have an appreciable degree of cross-reactivity with molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)-derived epitopes were identified in five chimpanzees that were recently convalescent from acute HBV infection. Because the Patr alleles studied herein were found to be very common in two different chimpanzee populations, the present data should facilitate the use of chimpanzees for immunological studies.

Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide.

Dendritic cells (DCs) are potent antigen-presenting cells, which have recently been applied for cancer immunotherapy using epitope peptides. Accumulating results of the clinical trials of such a strategy suggest that maturity of the applied DCs has a significant impact on the outcome of the vaccination. Here we examined the effects of penicillin-killed Streptococcus pyogenes (OK-432) on DC maturation and functions including induction of CTLs. DCs generated from peripheral blood using granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 showed immunophenotypes consistent with immature DCs (iDCs). These iDCs were further incubated with medium alone, tumor necrosis factor alpha, lipopolysaccharide, or OK-432. The immunophenotypical analysis showed DCs stimulated with OK-432 (OK-DCs) possessed significantly higher expression of CD83 compared with unstimulated DCs. Furthermore, OK-DCs showed significantly higher production of IL-12 and IFN-gamma compared with DCs with other stimulations. These results indicate that OK-432 stimulates iDCs to have a mature phenotype and to produce a significant amount of T-helper 1-type cytokines. To examine the potency of OK-DCs on the induction of specific CTLs, the tumor rejection peptide derived from carcinoembryonic antigen was used as a model antigen. The HLA-tetramer assay showed that potent CTL was induced with OK-DCs at high frequency. These results indicate that OK-432 efficiently stimulates DCs without interfering with the presentation of pulsed peptide. Furthermore, OK-432 does not activate nuclear factor kappaB through Toll-like receptor 2 or Toll-like receptor 4 in the indicator cell system; however, it induces IL-12 production through the beta(2) integrin system on DCs. These results strongly suggest that OK-432 could be applied to develop an efficient cancer vaccine using DCs pulsed with tumor rejection peptides.