Search

Tyrosine kinase inhibitors (TKIs) such as imatinib improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). However, treatment options for GISTs are still limited, and the continuation of TKIs is difficult due to adverse events in some cases. The effectiveness of low-dose imatinib is unclear. We report 2 cases to show effectiveness of low-dose imatinib in patients with adverse events. The first case is a male in his early 60s with a history of intestinal GIST resection who was diagnosed with recurrent GIST with peritoneal dissemination. He was started on low-dose imatinib (300 mg) because of a history of subconjunctival hemorrhage after receiving postoperative imatinib. Follow-up contrast-enhanced ultrasonography revealed that the tumors had shrunk in size and number after 2 months of treatment with 300-mg imatinib. He continued this treatment and showed partial response for 8 months. The second case is a female in her late 70s with rectal GIST who was treated with imatinib 400 mg. Due to a severe skin lesion, she changed her treatment to sunitinib 2 months after initiation. However, new metastasis in the liver was confirmed after 4 months of administration of sunitinib. She underwent surgical esection of the rectal tumor to reduce the volume. After the surgery, low-dose imatinib (300 mg) with oral steroids was adopted. Follow-up confirmed the absence of recurrence at the rectum and no increase in hepatic tumor size for 18 months. Aggressive treatment with low-dose imatinib instead of discontinuation or alteration of treatment may benefit patients with unresectable and postoperative GISTs with sensible mutation to imatinib.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The serum level of soluble CD163 (sCD163), a macrophage activation marker, is associated with liver tissue changes; however, its prognostic value is unknown. Here, we determined the utility of sCD163 as a marker for hepatocellular carcinoma (HCC) and prognostic marker for NAFLD. Methods This retrospective study obtained data regarding serum sCD163 levels, liver histology, and background factors associated with NAFLD in 287 patients (men/women, 140/147; average age, 53 ± 14 years) with NAFLD who underwent liver biopsy. Repeated liver biopsies of 287 patients with NAFLD (5.0 ± 2.7 years) were compared regarding serum sCD163 levels and liver tissue changes (stage, grade, steatosis, and NAFLD activity score). Results Serum sCD163 levels increased with the progression of liver fibrosis and inflammation (both P Conclusions The serum sCD163 level reflects the progression of fibrosis and inflammation in liver tissues, showing much promise as a noninvasive biomarker for nonalcoholic steatohepatitis and NAFLD as well as a possible predictor of HCC development and patient prognosis.

Afferent-loop syndrome (ALS) is known as a rare complication of partial or total gastrectomy and also occurs after pancreatoduodenectomy. The symptoms of ALS vary with the location of the mechanical obstruction, and the choice of therapeutic method should reflect the patient’s condition and disease state. Herein, we report the use of endoscopic ultrasound (EUS)-guided afferent loop drainage with a plastic stent and its reintervention for malignant ALS. An 80-year-old man was admitted to our hospital with abdominal pain. Thirty-two months before, the patient underwent left hepatectomy with choledochojejunostomy and Roux-en-Y reconstruction for hilar biliary adenocarcinoma. An abdominal CT scan showed a dilated afferent loop and a low-density lesion in the peritoneum that suggested recurrence of hilar biliary adenocarcinoma and malignant ALS due to mechanical obstruction of the afferent loop caused by peritoneal dissemination. The recurrence site did not include the choledochojejunostomy anastomosis and was far distal to it. We employed a convex EUS scope and directly punctured the afferent loop from the stomach. We inserted one double pig-tail stent, and the ALS immediately improved. Five months later, ALS recurred, and we exchanged a plastic stent through the fistula. After reintervention, ALS did not recur before the patient’s death due to cancer progression.

The majority of patients with eosinophilic esophagitis (EoE) are likely to have observable features under narrow-band imaging, namely beige mucosa. However, the histological features and clinical implications of beige mucosa have not been investigated. The aim of this study was to determine whether beige mucosa could serve as an endoscopic marker for predicting active inflammatory sites of EoE.We retrospectively analyzed both the narrow-band images and biopsied specimens of 77 esophageal lesions from 35 consecutive patients with EoE. We divided these specimens into two groups: target biopsied specimens from beige mucosa (beige group) and specimens biopsied from non-beige mucosa (non-beige group). The number of eosinophils per high-powered field, thickness of the superficial differentiated cell layer, and depth of the hemoglobin component from the surface layer were compared between the two groups.Forty-four out of the 45 specimens were diagnosed as histological active lesions in the beige group. The sensitivity, specificity, and overall accuracy of beige mucosa in predicting EoE activity were 97.8%, 96.9%, and 97.8%, respectively. Compared with the non-beige group, specimens in the beige group had a significantly thinner superficial differentiated cell layer.Beige mucosa is associated with thinning of the normal superficial differentiated cell layer, and these histological changes in the active inflammatory sites of EoE could be recognized endoscopically as color differences. Beige mucosa may serve as an endoscopic indicator for predicting the histological activity of EoE.

The incidence of eosinophilic esophagitis (EoE), a Th2-type allergic disease of the esophagus, has increased with the higher prevalence of gastroesophageal reflux disease (GERD). Both conditions are chronic inflammatory diseases with similar clinical presentations, yet their pathogenesis is thought to differ. Recent evidence indicates that forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) play a critical role in immune tolerance and control of Th2-biased responses in various allergic diseases.This study aimed to investigate differences in Treg induction between EoE and GERD and clarify whether this difference was related to the clinicopathological findings of patients with EoE.Thirty patients (15 men, 15 women) with EoE and 30 patients (15 men, 15 women) with GERD were included. Patient characteristics, including endoscopic and pathological findings, were compared between the two groups. Immunohistochemistry staining was used to identify T lymphocytes and Tregs. Tregs were identified by CD3 + FOXP3 + staining, and T cells were defined as CD3 + cells. The number of T cells and Tregs in the epithelium was counted, and the average of Tregs/T cells was calculated.The ratio of Tregs/CD3 + T cells in the esophageal epithelium was significantly lower in the EoE group than in the GERD group (9.9% vs. 23.6%, P = 0.0000012). Comparison of the ratio of Tregs/CD3 + T cells by age, gender, endoscopic findings, and histological findings in patients with EoE revealed a significant difference in gender.Treg induction was impaired, and this effect was more pronounced in male adult patients with EoE than those with GERD.

We report three Japanese cases with increased colonic 18-fluorodeoxyglucose (FDG) uptake in association with melanosis coli. Case 1: A 56-year-old woman received 18-FDG positron emission tomography (PET) for comprehensive medical checkup. Case 2: A 79-year-old man received FDG PET for follow-up evaluation for intestinal cancer. Case 3: A 51-year-old woman received FDG PET for medical checkup. Each showed increased cecal/ascending colonic uptake without any colonic wall changes. Colonoscopy detected melanosis coli where FDG uptake was demonstrably increased. Neither malignancy nor inflammatory response were confirmed. Succeeding follow-ups showed neither malignant nor inflammatory lesions in any of the patients.

Esophageal squamous cell carcinoma (ESCC) is the seventh most common cancer and the sixth leading cause of cancer-related death worldwide, and has a male preponderance. The gender-based differences in clinical presentation and risk factor exposure are not fully studied. The aim of this study was to compare males and females with this disease. We retrospectively investigated the clinical data of 503 consecutive patients with ESCC from April 2011 to December 2019. Data collected included patient demographics, clinical presentation, pathology and risk factor exposure. We analyzed the differences in clinical characteristics and risk factor exposure between males and females with ESCC. Four hundred and sixty-nine patients with ESCC were included. The male to female ratio was 4.6:1. There was no significant difference in clinical presentation and pathology. There were significant differences between risk factor exposure between the two genders: smoking and alcohol consumption was an association in more than 90% of males but in less than 50% of females. The analysis including all patients showed no significant difference in survival rates, but when limited to patients with stage 3 or higher disease, survival rates were significantly higher in females (Figure). Smoking and alcohol consumption, traditionally considered risk factors, are less associated with female patients with ESCC, and other environmental risk factors might be more involved in this gender.

The association between melanosis coli (MC) and colorectal neoplasms remains unclear. Thus, we primarily aimed to clarify the epidemiology of MC in the Japanese population, identify the relationship between the use of anthranoids and MC, and determine the prevalence of detected intestinal lesions in patients with MC. We subsequently conducted a meta-analysis of published data, including our results, to summarize the influence of MC on the prevalence of colonic neoplasms. We conducted a retrospective survey in Japan to investigate the effects of MC on intestinal disorders. The prevalence of colorectal neoplasms and ileal ulcers was evaluated by colonoscopy, and the clinical characteristics of the participants were investigated using an electronic database. Odds ratios for colorectal neoplasms were calculated. We also performed a meta-analysis using Review Manager to reveal the comprehensive relationship between MC and colorectal neoplasms. We enrolled 690 Japanese participants in the primary study. The prevalence of regular anthranoid use was significantly higher in the MC group than in the control group (50.9% vs. 6.5%, p

Ischemic enteritis (IE) is a rare disorder which is caused by inadequate blood flow to small intestine. The diagnostic procedure of this disease has not sufficiently established because of its rarity. Here, we report a case of IE in a hemodialysis-dependent 70-year-old man and summarize the diagnostic options for IE. The patient was admitted to our hospital because of acute abdominal distention and vomiting. He presented with mild tenderness in the lower abdomen and slightly elevated C-reactive protein level as revealed by blood tests. Radiographic imaging showed small bowel obstruction due to a stricture in the distal ileum. Contrast-enhanced abdominal ultrasonography revealed a 7-cm stenotic site with increased intestinal wall thickening, which preserved mucosal blood perfusion. Elastography revealed a highly elastic alteration of the stenotic lesion, indicating benign fibrotic changes resulting from chronic insufficient blood flow. Based on a clinical diagnosis of IE with fibrous stenosis, a partial ileostomy was performed. After surgical treatment, oral intake was initiated without recurrence of intestinal obstruction. Pathological findings revealed deep ulceration with inflammatory cell infiltration at the stenotic site. Occlusion and hyalinization of the venules in the submucosal layer indicated IE. In addition to current case, we reviewed past case reports of IE. Through this case presentation and literature review, we summarize the usefulness and safety of transabdominal ultrasonography for diagnosing IE.

Obstructive jaundice induced by pancreatic adenocarcinoma is typically treated with biliary drainage with endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary drainage (ERCP-BD). Recently, endoscopic ultrasonography-guided biliary drainage (EUS-BD) was employed as an alternative method after ERCP-BD failed. We aimed to determine the efficacy and safety of EUS-BD for primary biliary drainage.Between December 2011 and February 2019, at Kawasaki General Medical Center, we retrospectively enrolled 33 patients who had undergone endoscopic biliary drainage with a metal stent, in a first attempt to relieve obstructive jaundice caused by unresectable pancreatic adenocarcinoma. We compared the technical and clinical outcomes between ERCP-BD and EUS-BD.Twenty-three patients underwent ERCP-BD and 10 underwent EUS-BD. Both groups achieved 100% technical success. The clinical success rates were similar between the groups: 91% (21/23 patients) for ERCP-BD and 100% (10/10 patients) for EUS-BD (We suggest that EUS-BD could be employed for primary biliary drainage in patients with obstructive jaundice caused by unresectable pancreatic adenocarcinoma.

Objective Recent studies have found higher rates of autoimmune diseases, such as celiac disease, Crohn's disease, and ulcerative colitis, in patients with eosinophilic esophagitis (EoE) than in the general population. This study investigated the concomitant rate of autoimmune disease among Japanese patients with EoE and evaluated the clinicopathological characteristics of EoE patients with autoimmune disease. Methods The medical records of patients diagnosed with EoE between April 1, 2016, and June 30, 2020, were reviewed. We analyzed the concomitant rate of autoimmune diseases in patients with EoE and compared the clinical and histological differences between patients with and without autoimmune disease. Results Sixty-four patients with EoE were enrolled. Of them, 1 had ulcerative colitis (1.6%), 1 had autoimmune polyendocrine syndrome type 2 (1.6%), and 6 had endometriosis (28.5% of women, 44.4% of reproductive-aged women). No significant differences in the clinical course or histological findings were found between EoE patients with and without autoimmune diseases. No complications, including stenosis, were seen in EoE with autoimmune disease, and most patients with EoE and autoimmune diseases were responsive to proton pump inhibitors (PPIs). Conclusion In this study, 8 out of 64 patients with EoE had an autoimmune-related disease, including ulcerative colitis (n=1, 1.6%), autoimmune polyendocrine syndrome type 2 (n=1, 1.6%), or endometriosis (n=6, 44.4% of women of reproductive age), which is higher than that previously reported in the general population. Further investigations are required to clarify the relationship between EoE and autoimmune diseases.

Background: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM). Aims: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). Methods: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. Results: There were no differences in MAM composition between terminal ileum and sigmoid colon according to β-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group. Conclusion: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.

Background/Aims Food interaction, including food hypersensitivity, plays a key role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). Since only a few studies have been reported about the relationship between food hypersensitivity and IBS-D, we elucidate the prevalence of serological food hypersensitivity in patients with IBS-D and the characteristics of gastrointestinal symptoms and serum cytokine profiles in patients with IBS-D and serological food hypersensitivity. Methods Immunoglobulin E (Ig E)-mediated serological food hypersensitivity and serum cytokine levels were evaluated using the multiple allergen simultaneous test evaluating food allergen-specific serum IgE and Luminex Milliplex Panel containing multiple fluorescence-labeled beads. Class 2 or above was considered as IgE-mediated food hypersensitivity positive. The gastrointestinal symptom rating scale was used to evaluate symptoms. Results We enrolled 92 subjects, including 60 with IBS-D and 32 healthy controls. The percentages of patients with IgE-mediated serological food hypersensitivity were not significantly different between the groups (controls = 28.1% and IBS-D = 33.3%). Serum IL-1β, IL-6, IL-8, macrophage inflammatory protein-1alpha, and TNF-α levels were higher in patients with IBS-D than in controls. Serum concentration of TNF-α (43.4 vs 21.8 pg/mL, P = 0.009) was higher in patients with IBS-D without IgE-mediated serological food hypersensitivity than those with food hypersensitivity. Conclusions One-third of Japanese patients with IBS-D showed IgE-mediated serological food hypersensitivity. The serum cytokine profile differed and was characterized by lower inflammatory cytokine levels in IBS-D with IgE-mediated serological food hypersensitivity. Serological test regarding IgE-mediated food hypersensitivity can detect a certain cluster of IBS-D.

Barrett’s esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with ‘collagen metabolic process’ and ‘multicellular organismal macromolecule metabolic process’ as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. University Hospital Medical Information Network (UMIN) (000004004).

A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy.

Background/Aim: The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs. Methods: Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood. Results: A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32–8.47), women (OR 2.22; 95% CI 1.33–3.72) and corpus atrophy (OR 1.82; 95% CI 1.14–2.90). Conclusion: PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.

The gastrointestinal symptoms of irritable bowel syndrome are strongly related to impaired quality of life (QOL), especially in diarrhea-predominant. The gene polymorphisms associated with serotonin, or 5-hydroxytryptamine, alter gastrointestinal symptoms and mental status. We aimed to evaluate the effects of gene polymorphisms on gastrointestinal symptoms, psychological conditions, and QOL, and compare these between patients with diarrhea-predominant irritable bowel syndrome (n = 62) and healthy controls (n = 64). The gene polymorphisms of 5-HTTLPR, 5-HTTVNTR, TPH1 rs453773, and TPH1 rs211105 were evaluated. Gastrointestinal symptoms, depressive state, and QOL were assessed using the Gastrointestinal Symptom Rating Scale, Self-rating Depression Scale, and Short-Form-36. Gene polymorphisms did not significantly differ in frequency between the two groups. The scores for diarrhea, abdominal pain, and indigestion significantly correlated with the physical component summary score. Only the group of patients with diarrhea-predominant irritable bowel syndrome showed a significant correlation between the TPH1 rs211105 T/T genotype and lower scores for role physical and mental health, and higher scores for indigestion and diarrhea. 5-HTTLPR l/s was associated with lower score of role emotional in the diarrhea-predominant irritable bowel syndrome and higher scores in the controls. The gene polymorphisms of 5-hydroxytryptamine signaling effected gastrointestinal symptoms and QOL, especially of the patients with diarrhea-predominant irritable bowel syndrome.

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved for Helicobacter pylori eradication therapy in Japan.To compare PPI- and P-CAP-containing triple therapy and vonoprazan-based triple therapy.Two hundred ninety-five initial subjects received a PPI-containing triple therapy; the next 125 subjects received vonoprazan-containing triple therapy. Two sequential groups received 7-day eradication regimens consisting of amoxicillin 750 mg, clarithromycin 200 mg both twice a day with standard dose PPI or vonoprazan (20 mg) each twice daily. H. pylori eradication was confirmed by a 13C-UBT. Clarithromycin susceptibility was evaluated by 23S rRNA PCR.Population cure rates with clarithromycin susceptible strains were 89.6 versus 100 % for PPI and vonoprazan therapies, respectively. Cure rates with resistant strains were 40.2 % with PPI therapy versus 76.1 % with vonoprazan triple therapy. There was no difference in side effects.Although 7-day P-CAB triple therapy was superior to 7-day PPI triple therapy, neither was highly effective, or can be recommended, in the presence of clarithromycin-resistant infections.