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Background: Visceral hypersensitivity is one of the mechanisms of irritable bowel syndrome (IBS), but it does not explain the entire symptomatology, i.e., altered bowel habit with abdominal pain relieved by defecation. We tested our hypothesis that an abnormal link between luminal stimulation and mural response may have some role in the pathophysiology of IBS.Methods: Patients with IBS (n = 10, median 21 years old, 5 male patients, 5 female patients) and healthy control subjects (n = 10, median 21 years old, 5 men, 5 women) were studied. A manometric catheter with three transducers was inserted to the descending colon and a balloon was placed in the distal sigmoid colon. Another catheter with three transducers was inserted to the duodenum. After baseline for 30min, the sigmoid colon was stimulated by balloon distention for 30min followed by recovery for 30min. Balloon distention was repeated 100 times, and each stimulation consisted of a 5-s inflation and a 10-s deflation, with a volume of 50ml maximum. The sensory threshold of balloon inflation was then examined, and plasma adrenocorticotropic hormone (ACTH) was measured with radioimmunoassay.Results: Repetitive colonic distention induced a significant increase in motility indices (mmHg s/s%) of the descending colon in the IBS patients (from 118 +/- 25 to 333 +/- 108, P < 0.05) but not of those in controls (from 90 +/- 16 to 89 +/- 19). A significant group difference (P < 0.05), period effect (P < 0.02), and group x period interactions (P < 0.01) were detected with two-way ANOVA. Duodenal motility indices in controls were significantly reduced by colonic distention (from 169 +/- 25 to 104 +/- 14, P < 0.01), but those in the IBS patients were not (from 156 +/- 17 to 124 +/- 20). The sensory threshold of balloon inflation in the IBS patients (74 +/- 10ml) was significantly lower than that in controls (125 +/- 6ml, P < 0.001). There was no significant difference in plasma ACTH levels between the IBS patients and controls.Conclusions: Repetitive distention of the distal sigmoid colon below the sensory threshold induced orad exaggerated motility of the colon in IBS patients. The distention inhibited motility of the small intestine in healthy subjects, but this inhibition was blunted in IBS patients. These results suggest that IBS patients may have not only visceral hypersensitivity, but also an abnormal intestinal reflex. [ABSTRACT FROM AUTHOR]

The expression of manganese superoxide dismutase (Mn-SOD) was studied immunohistochemically, using a specific monoclonal antibody, in surgically resected hepatocellular carcinoma (HCC) and noncancerous tissues from 47 patients (2 with well-differentiated HCC, 36 with moderately differentiated HCC, 8 with poorly differentiated HCC, and 1 with undifferentiated carcinoma). Cancer cells in 44 patients (93.6%) were positive for Mn-SOD. The staining pattern of cancer cells was mostly homogeneous in well-differentiated HCC, whereas it was heterogeneous in poorly differentiated HCC. Moreover, strongly positive immunoreactivity was observed in noncancerous liver tissues in all patients, especially in normal hepatocytes surrounding HCC, regenerative small hepatocytes in the tumor boundary, and mononuclear inflammatory cells in the necroinflammatory lesions. The positive immunoreactivity for Mn-SOD in patients with HCC appears to reflect increased production of the enzyme protein. [ABSTRACT FROM AUTHOR]

Backgrounds: Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan., Methods: A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE., Results: Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone., Conclusions: Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE., (© 2024. Japanese Society of Gastroenterology.)

New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.

Chronic inflammatory bowel disease (IBD) is an important etiologic factor in the development of colorectal cancer. However, the mechanism underlying the development of colorectal cancers through chronic inflammation is not known. Activation-induced cytidine deaminase (AID) was originally identified as an inducer of somatic hypermutation in the immunoglobulin gene. We recently found that the mutagenic activity of AID expression links inflammation to the development of cancer. Aberrant AID expression is triggered by hepatitis C virus infection in human hepatocytes or Helicobacter pylori infection in human gastric epithelial cells, and leads to the generation of somatic mutations in various tumor-related genes. Here, we review our findings relating to how AID contributes to the development of colitis-associated colorectal cancers (CACs). Immunohistochemistry revealed the enhanced expression of endogenous AID protein in not only in the inflamed colonic mucosa of ulcerative colitis patients but also CAC tumor lesions. Pro-inflammatory cytokine TNF-α induced strong aberrant expression of AID via IκB kinase-dependent NF-κB-signaling pathways in human colonic epithelial cells. Furthermore, AID expression was also elicited in response to the T helper cell-2-driven cytokines IL-4 and IL-13, which are activated in human IBD. Aberrant activation of AID in colonic cells preferentially evoked genetic mutations in the TP53 gene, whereas there were no nucleotide alterations of the APC gene. These findings suggested that pro-inflammatory cytokine-mediated aberrant expression of AID in colonic epithelial cells plays a role as a genotoxic factor that enhances genetic instability during chronic colonic inflammation, leading to CAC development.

A solid pseudopapillary tumor (SPT) of the pancreas is a rare type of pancreatic neoplasm found predominantly in young women. SPTs typically behave as though benign; however, in some cases they also have malignant potential. We encountered a rare case of a recurrent SPT that developed 4 years after the initial surgery in an elderly male patient. Abdominal computed tomography (CT) revealed that the 61-year-old patient had four intra-abdominal masses, suggesting a recurrence of SPT. The patient had a history of distal pancreatectomy due to SPT in the pancreatic tail 4 years previously. These tumors showed positive signals on diffusion-weighted magnetic resonance imaging (MRI), and were treated successfully by aggressive surgical resection. Microscopic diagnosis was compatible with recurrent tumors of SPT. A chemosensitivity test, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST), showed that the resected tumors were sensitive to several antitumor drugs. We suggest that the CD-DST may be used to indicate promising antitumor agents for treating SPTs with malignant tendencies. In addition, a diffusion-weighted MRI can be useful for accurately visualizing SPTs of the pancreas.

Background: Instruments for measuring the presence and severity of specific irritable bowel syndrome (IBS) symptoms, comparable to those used in Western countries, have been lacking in Japan. The aim of this study was to develop, validate, and confirm the reliability of the Japanese version of the Rome II modular questionnaire for IBS (RIIMQ-J) and the IBS severity index (IBSSI-J)., Methods: Forty-nine patients in the university hospital with chronic or recurrent abdominal pain and discomfort and/or altered bowel habits were enrolled. With Rome II criteria, 27 patients were diagnosed as having IBS, and the other 22 patients were evaluated as having other functional bowel disorders (FBDs). The English versions of RIIMQ and IBSSI were translated into Japanese. After back-translation and approval of the questionnaire, subjects completed both questionnaires twice within 14 days., Results: Cronbach's alpha of the RIIMQ-J was high (0.72). The sensitivity of RIIMQ-J for the diagnosis of IBS was also high (89%). The specificity of RIIMQ-J for denial of IBS among patients with other FBD was satisfactory (73%). The IBSSI-J showed high internal consistency (0.69) and reproducibility (intraclass correlation coefficient, 0.86, P < 0.001)., Conclusions: The RIIMQ-J and IBSSI-J are valid, reliable, and appropriate instruments for detecting and assessing the severity of IBS status in Japanese patients.

Background: Acute necrotizing esophagitis (ANE) is a rarely described entity that is thought to be a cause of upper gastrointestinal (UGI) bleeding, The present study examined the incidence of ANE among patients with UGI bleeding, as well as the clinical features of ANE, and the coexisting illnesses and medication histories of ANE patients., Methods: A retrospective analysis of clinical and endoscopic findings and the clinical course in 16 patients with ANE was carried out over a 3-year period., Results: We observed 16 patients (6%) of ANE in 239 patients with UGI bleeding during the 3-year period. The average age of the patients was 62.5 years. The lesions predominantly affected the lower third of the esophagus, and hiatal hernia was the most common (63%) coexisting endoscopic finding. All patients had coexisting disease. Fifty percent of patients with ANE (eight patients) had taken nonsteroidal anti-inflammatory drugs (NSAIDs). ANE also occurred in four patients with diabetic ketoacidosis. Supportive therapy, including parenteral nutrition and administration of a proton pump inhibitor, was effective., Conclusions: ANE is more common than has been previously reported, and it should be included in the differential diagnosis of UGI bleeding. ANE could be characterized as an "acute esophageal mucosal lesion," particularly in aged patients with hiatal hernia and among those who consume NSAIDs.

Background: Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro., Methods: Tumor sections from 79 patients who underwent endoscopic mucosal resection for early intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on COX-2 expression and activity in human gastric cell lines., Results: Among the 79 early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions) and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2 immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in early gastric cancer located in the gastric pylorus, compared with that in the other locations. In human gastric cell lines, bile acids induced COX-2 expression, mediated by the ERK 1/2 mitogen-activated protein kinase pathway., Conclusions: COX-2 expression is elevated in early gastric cancer of the gastric pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in human gastric cell lines, suggesting a role of bile reflux in gastric carcinogenesis.

Background: We examined bacterial translocation (BT) by acute ethanol administration, using a peptidoglycan detecting system., Methods: Rats were given 20% (v/w) ethanol (10 ml/kg body weight), and heparinized samples of portal blood were collected at specific time points after administration. Plasma peptidoglycan, beta-glucan, and endotoxin concentrations of portal blood were measured. The rats were divided into three groups: a 20% ethanol group (20ET group), a 5% ethanol group (5ET group), and a control group. The groups were given 10 ml/kg body weight of either 20% (v/w) ethanol (20ET group), 5% (v/w) ethanol (5ET group), or distilled water (control group). Femoral arterial blood, portal blood, mesenteric lymph nodes (MLNs), spleen, and liver were cultured to assess BT. Plasma peptidoglycan, beta-glucan, and endotoxin concentrations of femoral arterial blood and portal blood were measured., Results: The plasma peptidoglycan concentration of portal blood was significantly increased 24 h after the administration of 20% ethanol. There was no significant difference in the incidence and magnitude of viable BT to the MLNs, spleen, and liver among any of the groups at this time point. The rate of plasma peptidoglycan positivity and the plasma peptidoglycan concentration were increased significantly in the portal blood of the 20ET group 24 h after administration., Conclusions: Peptidoglycan was translocated into the portal blood by acute administration of 20% ethanol. Our findings suggest that viable bacterial flora may translocate from the intestine under the influence of ethanol, and BT may be one of the causes of chronic alcoholic liver disease.

Gastrointestinal stromal tumor (GIST) in the distal third of the rectum was detected in a 57-year-old man who underwent an abdominoperineal resection of the rectum. Because the tumor expressed CD34 and c-kit gene product, but did not express smooth muscle actin or S-100 protein, it was diagnosed as an uncommitted type of GIST. Moreover, a specific mutation in the sequence coding the juxtamembrane domain in exon 11 of the c-kit proto-oncogene was revealed by a polymerase chain reaction-single-strand conformation polymorphism method. One year after resection, the patient developed multiple liver metastases. It is suggested that a specific mutation in exon 11 of the c-kit proto-oncogene may have played an essential role in the development of the liver metastases.