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Anti-tumor necrosis factor-α (TNF-α) is a principal treatment for Crohn's disease (CD). However, it increases the susceptibility to tuberculosis (TB) infection, and therefore, screening examination prior to treatment initiation is crucial. Here, we report the case of a patient with CD who developed pulmonary TB following anti-TNF-α therapy, despite negative screening. A 19-year-old female who had no history of TB or had traveled to TB-endemic regions was diagnosed with CD. After negative TB screening with chest X-ray and interferon-gamma release assay, the patient was initiated on oral prednisolone and pH-dependent mesalazine. The treatment was changed to infliximab (IFX) because of the inadequate response observed to prednisolone;however, she developed pulmonary TB only 10 weeks after the initiation of IFX. The standard short-course anti-TB regimen was initiated to treat pulmonary TB, whereas IFX was discontinued and replaced with budesonide. Our case suggests that the risk of developing TB should not be excluded, despite the initial negative TB screening, particularly when a patient develops respiratory symptoms during anti-TNF-α therapy.

The causes of IBD (inflammatory bowel disease), ulcerative colitis and Crohn's disease, have not been elucidated. It is thought that the pathogenesis involves genetic predisposition, environmental factors and host immune response to food antigens and microbiota. Most of IBD susceptiblity genes are related to function of immune cells, maintenance of homeostasis of epithelial cells, autophagy, ER stress and so on. These genetic abnormalities may induce abnormal immune response to antigens and intestinal bacteria, which are modified by diet habit and hygiene environment. Recently, the interrelationship between intestinal bacteria and hosts has dramatically been elucidated, and breakdown of the homeostatic mechanisms at the cellular level is revealed to have an important role in the onset of IBD.

The clinical and pathological features of human intestinal spirochetosis (HIS) are not well known. Here we report 55 patients with HIS who were diagnosed at our institution during the past 5 years. Seven patients presented with symptoms such as abdominal pain or diarrhea, while the others were incidentally diagnosed during screening colonoscopy. Most patients had non-specific endoscopic findings, including intestinal edema or erosion. The diagnosis of HIS was histologically confirmed via hematoxylin and eosin staining, periodic acid-Schiff staining, and/or immunohistochemistry using anti-Treponema pallidum antibody. Among the 55 patients, five were diagnosed with diseases other than HIS (amoebic colitis, three;ulcerative colitis, one). Sixteen patients were treated with either amoxicillin or metronidazole;only metronidazole proved to be effective. The clinical significance of asymptomatic HIS remains unknown. Some case reports suggest a risk for increased severity in patients with immunodeficiency and/or sexually transmitted diseases. Therefore, aggressive treatment for HIS should be considered, particularly in high-risk patients.

We conducted a retrospective study of the efficacy of a polyethylene glycol purge before colonoscopic examination in 110 patients with colonic diverticular bleeding. The patients' data were assessed for the timing of colonoscopy and the methods used to stop bleeding. The rate at which bleeding diverticula were identified was markedly higher when a purge was used than when it was not (28.2% vs. 12.0%, p=0.11). In addition, the identification rate was significantly higher when colonoscopic examination was performed within 18 hours of the final hematochezia than when it was performed after 18 hours (40.5% vs. 10.5%, p<0.01). These findings suggest that patients with diverticular bleeding should undergo colonoscopy following an orally administered colonic purge, providing their condition permits. Furthermore, colonoscopy should be performed within 18 hours of the final hematochezia in order to improve identification of the bleeding diverticulum.

We present a 35-year-old Japanese man with Crohn disease. He underwent ileocolectomy for ileum perforation when he was 28 years old, Crohn ileitis was diagnosed and medical treatment was commenced. When he was 35 years old, he complained of severe pain of the right upper torso and the left leg with no apparent trigger. A full check-up revealed that he had multiple fractures including a transcervical fracture of the left femur, ribs on both sides, and fracture of the sacroiliac joint. He had no history of prior use of steroids, and the fractures were thought to have been caused by vitamin D deficiency. This case suggests that clinicians should be aware of the possibility of osteomalacia caused by malabsorption of fat-soluble vitamin D when examining patients with ileocolic Crohn disease.

A 26-year-old Japanese woman was admitted to the hospital because of fever and general fatigue. A diagnosis of acute hepatitis B was given because of high levels of transaminase and positivity for HBs-Ag, HBe-Ag and HBc-IgM. On the 2nd day progression to fulminant hepatitis was suspected, and steroid pulse therapy, cyclosporin, entecavir, and interferon-β were started. Her laboratory data improved until transaminase showed an increase on 18th day, and steroid was once again administered. Abdominal CT scan and plain abdominal X-ray showed pneumatosis cystoides intestinalis (PCI) mainly along the ascending colon without any symptoms. After discontinuation of steroid therapy, abnormal gas gradually disappeared. This is a very rare case of PCI, which may have been caused by short-term steroid pulse therapy.

A 57-year-old man with advanced gallbladder cancer and accompanying hepatic, colonic and duodenal invasion and para-aortic lymph node metastasis was referred to our hospital. Gemcitabine plus S-1 administration was chosen. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1 and 15, and repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Chemotherapy was effective for the primary gallbladder tumor and lymph node metastasis. The primary tumor and metastatic lymph nodes were shown to have disappeared by a FDG-PET CT study after 10 courses of chemotherapy. Informed consent was obtained prior to performing surgery of the primary lesion. Pathological examination showed fibrosis and a small focus of residual cancer in the resected gallbladder. Complete resection was achieved as all the margins were negative. The findings suggest that gemcitabine plus S-1 treatment may be effective against advanced gallbladder cancer.

A 64-year-old male presented with discomfort in the chest. His endoscopic examination and CT scan showed esophageal cancer with multiple liver metastases. A total of ten courses of systemic chemotherapy by 5-fluorouracil (5-FU) (800 mg for five days) and cisplatin (CDDP) (80 mg/day on the first day of the week for four weeks) were performed, and liver and lymph node metastases disappeared. The primary lesion was the only site detected positive by PET scan. After a concurrent chemoradiation therapy, salvage endoscopic mucosal resection (EMR) was performed on the remainder of the primary site and the patient gained a complete response (CR). We report this case because, although the mean survival time of advanced esophageal cancer is less than one year, this patient responded to chemotherapy and gained complete response by salvage EMR. This patient has had no recurrence for four years since his initial diagnosis.

H. pylori infection elicits a chronic cellular inflammatory response not only in the gastric mucosa, but also in the extra-digestive organs. Indeed, H. pylori infection has been epidemiologically linked to the extra-digestive conditions and diseases. In this article, we review recent progress in our understanding about the relationship between H. pylori infection and lifestyle-related diseases, such as atherosclerosis, diabetes mellitus, obesity, hyperlipidemia, hypertension, and osteoporosis. Although the relationships between all of these diseases and H. pylori infection are still controversial, H. pylori infection may increase the risk for cardiovascular and cerebrovascular diseases, especially when CagA+ cytotoxic strains of H. pylori are present.

Recent advance of molecular biology and immunology contributes to the development biologics such as anti-TNFalpha agent in the treatment for inflammatory bowel disease (IBD). Although therapeutic strategy of IBD has not been changed for a long time, success of Infliximab, first anti-TNFalpha agent, now changes therapeutic strategy of IBD dramatically. Top-down strategy has been considered to improve patients' natural history in the therapy for Crohn's disease as well as in rheumatoid arthritis. Infliximab also has been expected as a promising medicine for pediatric Crohn's disease. Furthermore, Infliximab has been approved for the therapy of ulcerative colitis. These tremendous successes of Infliximab have encouraged us to develop other anti-TNF agents and other biologics. In this review, we describe current topics of biologics in IBD treatment and discuss future direction.

Recently prevalence of alcoholic liver disease has been increasing in Japan associated with an increase in alcoholic beverage consumption. In the present study, we addressed the recent trend in the etiology of liver cirrhosis (LC) in Japan, and investigated the influence of habitual drinking and viral hepatitis type C in the progression of LC. We carried out nation-wide survey by asking for the hospitals that are approved by the Japanese Society of Gastroenterology for the etiology of in-patients with LC, and compared to that in our hospital. Regarding the cases in nation-wide survey, 1274 cases (14%) of 9126 patients with LC were pure (without any markers of hepatitis virus) heavy drinkers, and 580 cases (6%) were heavy drinkers with any markers of hepatitis virus. However, in our general hospital, 24 cases of 101 patients with LC (24%) were pure heavy drinker, and 31 cases (30%) were heavy drinkers with any markers of hepatitis virus. In conclusion, although influence of hepatitis virus infection in alcoholic LC has been decreasing, it still plays an important role in the progression of alcoholic LC, especially in the general hospitals. Education of abstinence or low risk drinking is important not only heavy drinkers but also habitual drinkers with hepatitis virus infection.

In inflammatory bowel disease, such as Crohn's disease, certain immunological abnormalities are considered as its cause, but the fundamental mechanism remains unclear. However, recent researches revealed that inflammatory cytokines and adhesion molecules, such as TNFalpha, IL-6, IL-12 and alpha4 integrin, play an important role in the pathogenesis of Crohn's disease. This led to the development of anti-cytokine therapy and anti-adhesion molecules therapy using monoclonal antibodies to theses cytokines and adhesion molecules. Among them, infliximab, a chimeric monoclonal antibody to TNFalpha, is most clinically applied and marked therapeutic effect is seen in Crohn's disease. Moreover various anti-cytokine therapy was introduced in clinical fields.

Video capsule endoscopy (VCE) is a major advance in visualization of the small intestine and has been widely used for small intestinal involvement. We have developed a new capsule endoscope in collaboration with Olympus Medical Systems. Its features are, upgrade resolution, depth of the field, and brightness of the image, by improving the optical system, contained with the new function to adjust the level of lighting automatically coordinate with the brightness around, and original handy displayed real-time viewer. VCE is a new device which contributes to the diagnosis of nonsteroidal anti-inflammatory drug (NSAID) induced enteropathy, however, attention should be paid to retention of the capsule due to the stenosis of diaphragm induced by NSAID.

A variety of endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) have been developed as alternatives to PPI therapy or antireflux surgery. These techniques include the delivery of radiofrequency energy to the gastroesophageal junction, injection of agents into the lower esophageal sphincter zone, and suture plication of the proximal fundic folds. Each of these endoscopic techniques is designed to alter the anatomy or physiology of the gastroesophageal junction to decrease gastroesophageal reflux. However, only limited data are available on the mechanism of action of the various endoscopic techniques. Most studies of endoscopic therapy have only limited follow-up information, and safety issues remain unresolved. Further sham-controlled clinical trials will be required for endoscopic device and technique.

A 40-year-old man, who had suffered from general malaise and brown urine during his stay in China, was admitted with remarkable jaundice and hepatocellular disorders soon after he returned to Japan. Because his coagulation test results worsened, he was transferred to our hospital. No evidence of hepatitis A-D virus infection, autoimmune hepatitis, or metabolic disorders was noticed. His prothrombin time was extended (18%), grade II encephalopathy appeared on the second hospital day, and fulminant hepatitis was diagnosed. Artificial liver support was introduced, and his hepatic coma and coagulation parameters gradually recovered. Genotype IV hepatitis E virus RNA was detected in his early phase sera and also both IgG and IgM type anti-hepatitis E virus antibodies were detected. Fulminant hepatitis E resulting from infection in China was diagnosed.

The patient was a 50-year-old woman who suffered from gastric discomfort. She was first diagnosed as intrahepatic cholangiocarcinoma with hepatic, paraaortic lymphnodal and bone metastasis. Initial systemic chemotherapy using gemcitabine (GEM) and 5-FU failed to control the disease activity. Then she was given GEM and cisplatin (CDDP) combination chemotherapy. The response was assessed as stable disease (SD), but grade 4 leukopenia was seen. Then systemic therapy using GEM, and hepatic arterial infusion therapy with CDDP, l-leucovorin and 5-FU were continued biweekly. Partial response (PR) was achieved six months later, and her disease status was maintained as SD. This hepatic arterial infusion chemotherapy would be safe and feasible as therapy for inoperable intrahepatic cholangiocarcinoma.

Recently incidence of alcoholic liver disease (ALD) has been increasing in Japan associated with an increase in alcoholic beverage consumption. There have been a large number of reports about the relationship between alcohol and hepatocarcinogenesis, but it remains controversial. In the present study, we addressed the recent trend in incidence of ALD including liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in heavy drinkers in Japan. We carried out nation-wide survey by asking for the hospitals that are approved by the Japanese Society of Gastroenterology for recent aspects of in-patients with ALD. Except for HCC, percentage of ALD without viral hepatitis is more than 70%, which is increased when compared to the national survey carried out in 1992. In alcoholic LC patients, those who did not have viral hepatitis were 81%. However, the percentage of HCC without viral hepatitis was 34% of all of the heavy drinkers with HCC. Regarding the case in our university hospital, 138 cases (32%) of 432 patients with HCC were heavy drinkers. However, regarding in our general hospital, 15 cases of 23 patients with HCC (61%) were heavy drinkers. In conclusion, since the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers.

Nonalcoholic steatohepatitis (NASH) once considered a benign process is now known to lead to progressive fibrosis and cirrhosis. NASH is frequently associated with the metabolic syndrome. Gradual weight reduction and increased physical activity are always recommended in overweight patients, but not always effective in reversing NASH. Promising pharmacological treatments have been demonstrated with antioxidants, insulin sensitizers, hepatoprotectants, lipid-lowering agents, and antihypertensive drugs. The similar histological features and natural histories of alcoholic steatohepatitis (ASH) and NASH suggest that common pathogenic mechanisms might be involved in these two conditions. Therapeutic strategies targeting the common mechanisms may also have promising potential. A larger randomized-controlled trial is needed to definitively determine the efficacy of pharmacological treatments for NASH.

Chemotherapies for recurrent gastric cancer have not yet been established. Here we report a case of type 4 gastric cancer associated with lymphangitis carcinomatosis which became refractory to the previous chemotherapies. The case was a 40-year-old woman. She had been diagnosed with gastric cancer after a Krukenberg tumor operation. Chemotherapies (TS-1 plus CDDP as first-line, and TS-1 plus taxanes as second-line) were performed, and a partial response was achieved. Disease activity has been well controlled until this time. Since recurrence of left pleural effusion and lymphangitis carcinomatosis was recognized, we changed the chemotherapy TS-1 plus CPT-11. Pleural effusion decreased and lymphangitis carcinomatosis improved. The serum CA 19-9 level rose transiently after CPT-11 administration, and tended to fall at the second week of chemotherapy. However, the patient died 2 years 4 months after the onset. TS-1 plus CPT-11 combination chemotherapy would be effective for lymphangitis carcinomatosis and also useful as third-line chemotherapy for recurrent gastric cancer.