Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity.

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second-line steroid-therapy within the 2-years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non-SR (with first-line treatment 5-ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan-immune-markers of CD3, CD8, FOXP3, PD-1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene-expression-data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non-SR, SR had lower FOXP3 + Tregs (Odds-Ratio = 0.114, P = 0.002), PD-1 (OR = 0.176, P = 0.002) and CD163/CD68 M2-ratio (OR, 0.019, P = 0.019) but higher CD68 + pan-macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan-immune-markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan-macrophages but lower immune inhibitors of FOXP3 + Tregs, PD-1 and CD163/CD68 M2-macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid-requiring situation.

Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach With Low Acidity.

INTRODUCTION: Lipopolysaccharides (LPSs) of Gram-negative bacteria (GNB) are highly toxic and induce inflammation. Therefore, we investigated both the LPS activity and composition of GNB in the gastric fluid (GF) to assess the potential toxicity of them accumulated in the stomach. METHODS: GF and saliva samples were obtained from 158 outpatients who were undergoing upper gastrointestinal endoscopy and 36 volunteers using a nasogastric tube. The LPS activity was measured by assay kits including recombinant Factor C or Limulus amebocyte lysate. To assess the bacterial composition in the samples, a 16S ribosomal DNA-based operational taxonomic unit analysis was performed. We focused on the genera representing >0.1% of the whole microbiota. RESULTS: We found a high LPS activity in the GF samples with weak acidity (approximately > pH 4), whereas little/no activity in those with strong acidity (approximately < pH 2). Spearman test also demonstrated a close correlation between pH and LPS in those samples (r = 0.872). The relative abundance of GNB in the saliva showed no significant difference between the subject groups with weak- and strong-acidity GF. In addition, in the subjects whose GF acidity was weak, the GNB abundance in the GF was almost the same as that in the saliva. By contrast, in the subjects whose GF acidity was strong, the GNB abundance in the GF was significantly lower than that in the saliva. DISCUSSION: GNB that have recently moved from the oral cavity might account for the prominent LPS activity in a stomach with weak acidity.

A Case of Mesentero-axial Type of Acute Gastric Volvulus Successfully Reduced by a Balloon-assisted Endoscopy.

A 95-year-old man was admitted to the hospital due to a sudden onset of nausea and abdominal pain. Physical examination revealed abdominal distension with mild epigastric tenderness. Computed tomography showed a grossly distended stomach with displacement of the antrum above the esophago-gastric junction, and he was diagnosed with acute mesentero-axial gastric volvulus. We attempted urgent reduction using conventional endoscopy, but failed. He and his family did not want surgery because of his extreme advanced age, and a nasogastric tube was inserted to his stomach for decompression expecting a natural reduction. On the next day, however, it was not improved, so endoscopic reduction was tried again by a balloon-assisted endoscope without an overtube under X-ray fluoroscopy. When the scope reached the descending portion of the duodenum, the balloon on the scope tip was inflated, and the stomach position was reduced by pulling back the scope with twisting to the right. He was discharged from the hospital without any complication, and no recurrence has been observed for 12 months thereafter. We suggest a balloon-assisted endoscope as a useful tool for reduction of gastric volvulus especially in cases of reduction failure by a conventional one.

A Case-control Study on the Risk Factors for Ischemic Colitis.

OBJECTIVE: Ischemic colitis (IC) is a relatively common acute inflammation disorder of the intestine. It was considered to be a disorder of elderly people with risk factors for arteriosclerosis; however, a considerable number of young people with IC have been reported recently. We performed a case-control study to determine the risk factors for IC and compare the risk factors between elderly and non-elderly people. METHODS: The study included 209 consecutive patients diagnosed with IC between December 2004 and March 2017 at Tokai University Hospital. The study also included 209 randomly selected controls in the same calendar year so as to match age and sex. Possible risk factors for IC were identified and compared between age groups. RESULTS: The mean age of IC group was 64.9 with 60 males and 115 elderly patients aged 65 or more in each group. On multivariable conditional logistic regression analysis, drinking, abdominal surgery, hypertension, and malignant diseases were risk factors for IC in all ages. In non-elderly patients, only hypertension and laxative/enema use were significant factors, while in elderly, abdominal surgery, hypertension, COPD, malignant disease and antiplatelet drugs were significant. CONCLUSION: The risk factors in elderly people might be quite different from younger ones, while hypertension seemed to be a common risk in all ages.

A Case of Pedunculated Esophageal Leiomyoma Successfully Treated by Endoscopic Mucosal Resection.

Leiomyoma is one of the most commonly observed esophageal submucosal tumors, often appearing as a smooth-surfaced and semicircular protruded lesion. It sometimes grows toward the esophageal lumen and may be pedunculated in rare cases. We encountered a case of a pedunculated esophageal submucosal tumor diagnosed before treatment as a leiomyoma originating in the muscularis mucosae of a 68-year-old man. As the tumor arose in the muscularis mucosae, it could be safely resected via an endoscopic procedure. Only one case of pedunculated leiomyoma has been reported to date, and we herein report the second case, which was successfully treated by a minimally invasive endoscopic technique.

Usefulness of Acoustic Monitoring of Respiratory Rate in Patients Undergoing Endoscopic Submucosal Dissection.

Aim. The study assessed the usefulness of a recently developed method for respiratory rate (RR) monitoring in patients undergoing endoscopic submucosal dissection (ESD) under deep sedation. Methods. Study subjects comprised 182 consecutive patients with esophageal cancer or gastric cancer undergoing ESD. The usefulness of acoustic RR monitoring was assessed by retrospectively reviewing the patients' records for age, gender, height, weight, past history, serum creatinine, RR before ESD, and total dose of sedative. Results. Respiratory suppression was present in 37.9% of (69/182) patients. Continuous monitoring of RR led to detection of respiratory suppression in all these patients. RR alone was decreased in 24 patients, whereas both RR and blood oxygen saturation were decreased in 45 patients. Univariate analysis showed female gender, height, weight, and RR before treatment to be significantly associated with respiratory suppression. Multivariate analysis showed RR before treatment to be the only significant independent predictor [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.73-0.95, and P = 0.006] of respiratory suppression. Conclusion. In this study, the difference in RR before treatment between patients with and without respiratory suppression was subtle. Therefore, we suggest that acoustic RR monitoring should be considered in patients undergoing ESD under sedation to prevent serious respiratory complications.

Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study.

AIM: To evaluate the efficacy of adding irsogladine maleate (IM) to proton-pump inhibitor (PPI) therapy in non-erosive reflux disease (NERD) treatment. METHODS: One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM (group I) or rabeprazole plus placebo (group P). The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and the short form (SF)-36 quality of life questionnaires after four weeks of treatment. We also assessed whether patients with NERD with minimal changes (grade M) had different responses to the therapies compared with patients who did not have minimal changes (grade N). RESULTS: Group I and group P showed significant improvements in their FSSG scores after the treatment (from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P. Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N (modified Los Angeles classification) (7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041). The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores. CONCLUSION: The addition of IM to rabeprazole significantly improves gastroesophageal reflux disease symptoms and the quality of the lives of patients with NERD grade N.

Correlation between the Serum Pepsinogen I Level and the Symptom Degree in Proton Pump Inhibitor-Users Administered with a Probiotic.

In patients with functional upper gastrointestinal disorders such as gastroesophageal reflux disease and functional dyspepsia, the presence of symptoms is thought to occur in the absence of any organic diseases and the mechanisms behind this remain unclear. We therefore examined the relationship between stomach-related biomarker levels and symptoms. Twenty-four outpatients who had taken proton-pump inhibitors every day were enrolled in this study. The subjects consumed yogurt containing 109 colony-forming units of Lactobacillus gasseri OLL2716 (LG21) every day for three months. They underwent four clinical examinations in total. Each examination consisted of answering a questionnaire with a frequency scale for the symptoms of GERD (FSSG), and included measurements of the serum gastrin, ghrelin, and pepsinogens I and II levels. As a result, the FSSG score and the PGI value showed a decrease and an increase, respectively, after LG21 treatment when analyzed without age adjustment. A multiple regression analysis with additional adjustments for gender and age revealed a strong association between the PGI value and the FSSG symptom scores. Therefore either the PGI level itself or the factors regulating the PGI level might be involved in the etiology of these symptoms.

A case of small pancreatic cancer with intra-pancreatic metastasis diagnosed by endoscopic ultrasound.

INTRODUCTION: The usefulness of endoscopic ultrasound (EUS) in the diagnosis of small pancreatic cancer is widely accepted. We experienced a small, 8 mm, pancreatic cancer with intra-pancreatic metastasis of 2 mm revealed by EUS. The patient was a 71-year-old female with a small low echoic tumor observed by abdominal ultrasonography. She was referred to our hospital for further investigation. She complained of mild abdominal pain. She had a past history of myoma uteri. Ultrasonography showed a 10 mm low echoic mass in the body of the pancreas, but it was difficult to make a distinction between a solid mass and a cystic lesion. No tumor was shown by CT or MRI. EUS was performed, and showed a solid low echoic tumor of 8 mm and a low echoic mass of 2 mm in a diameter near the tumor. An ERCP study was performed, but the cytology of the normal main pancreatic duct was shown to be benign. We diagnosed the patient with pancreatic cancer, and surgery was performed. A pathological examination revealed a 10 mm invasive ductal carcinoma and intra-pancreatic metastasis.

Emergency upper gastrointestinal endoscopy in the Emergency Room of Tokai University Hospital.

The Tokai University Hospital is the only tertiary emergency hospital in the western region of Kanagawa prefecture and treats many patients; for example, more than 7,000 cases (including 297 helicopter-transfer cases) were transferred to the Emergency Room (ER) of the hospital in 2008. In cases where an emergency endoscopy is necessary, such as suspected upper gastrointestinal (UGI) tract bleeding, the gastroenterologists and the ER staff collaborate on patient care, diagnosis and treatment. The purpose of this study was to summarize such cases in the hospital and to elucidate the possible problems that such collaboration may cause, by means of a questionnaire completed by both the gastroenterology and the ER staff. There were 366 emergency upper GI endoscopies performed in the ER from April 2007 to October 2009, which included 163 hemostasis, 8 foreign body retrievals and 195 observation-only cases. After arrival of the patients, first the ER staff took care of them, then the gastroenterologist was called and both collaborated on the procedures to be implemented. The questionnaires revealed that, generally speaking, the collaboration worked well, but there were several problems that needed to be solved including maintenance, equipment supply and assistance of therapeutic endoscopy.