Search

Background: Since it is difficult for expert endoscopists to diagnose early gastric cancer in post-eradication status, it may be critical to evaluate the stratification of high-risk groups using the advance of gastric atrophy or intestinal metaplasia. We tried to determine whether the combination of endoscopic artificial intelligence (AI) diagnosis for the evaluation of gastric atrophy could be a useful tool in both pre- and post-eradication status., Methods: 270 Helicobacter pylori -positive outpatients (Study I) were enrolled and Study II was planned to compare patients ( n  = 72) with pre-eradication therapy with post-eradication therapy. Assessment of endoscopic appearance was evaluated by the Kyoto classification and Kimura-Takemoto classification. The trained neural network generated a continuous number between 0 and 1 for gastric atrophy., Results: There were significant associations between the severity of gastric atrophy determined by AI endoscopic diagnosis and not having a regular arrangement of collecting venules in angle, visibility of vascular pattern, and mucus using Kyoto classification in H. pylori -positive gastritis. There were significant differences ( p  = 0.037 and p  = 0.014) in the severity of gastric atrophy between the high-risk group and low-risk group based on the combination of Kimura-Takemoto classification and endoscopic AI diagnosis in pre- and post-eradication status. The area under the curve values of the severity of gastric atrophy (0.674) determined by the combination of Kimura-Takemoto classification and gastric atrophy determined by AI diagnosis was higher than that determined by Kimura-Takemoto classification alone in post-eradication status., Conclusion: A combination of gastric atrophy determined by AI endoscopic diagnosis and Kimura-Takemoto classification may be a useful tool for the prediction of high-risk groups in post-eradication status., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background and Aim: This study aimed to clarify whether several single-nucleotide polymorphisms (SNPs)-related chronic pancreatitis such as carboxypeptidase A1 ( CPA1 ), carboxypeptidase B1 ( CPB1 ), Gamma-glutamyltransferase 1 ( GGT1 ), G-protein-coupled receptor Class C Group 6 Member A ( GPRC6A ), and serine protease inhibitor, Kazal type 1 ( SPINK-1 ) genotypes were associated with clinical characteristics of patients with intraductal papillary mucinous neoplasm (IPMN) and worrisome features of IPMN., Methods: We enrolled 100 patients with IPMN and 116 patients as a control. Serum p-amylase, lipase, trypsin, phospholipase A2 (PLA2), and elastase-1 levels were measured. An Olympus EUS (GF-UCT 260) was used to perform endosonography in 100 patients with IPMN. Total EUS score was evaluated using endosonography. DNA was isolated from the duodenal tissue using a commercial system and polymerase chain reaction (PCR) was performed on 7500 Fast PCR System., Results: There were no associations between glucose tolerances, lipid levels and genotypes of CPA1 , GGT1 , GPRC6A , and SPINK-1 in patients with IPMN. CPA1 genotype was significantly associated with the pathophysiology of IPMN. Then, GGT1 genotype was also significantly associated with EUS total score and the size of cyst more than 20 mm and more than 30 mm as one of worrisome features of IPMN., Conclusion: Genotypes of carboxypeptidase A1 and gamma-glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of IPMN., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Although a new potassium-competitive acid blocker (P-CAB) vonoprazan has been developed in Japan, no data are available regarding long-term vonoprazan or vonoprazan and acotiamide combination treatment in patients with functional dyspepsia (FD)., Methodology: A total of 73 consecutive patients with FD diagnosed according to the Rome III classification were enrolled. Forty-two patients with FD were treated with vonoprazan monotherapy and thirty-one patients with FD were treated with vonoprazan and acotiamide combination therapy for 24 weeks. The levels of five pancreatic enzymes were measured, and the overall treatment efficacy (OTE) was defined as the ratio of FD patients with improved or unchanged in all items of GSRS and FD symptom scores after the treatment., Results: Treatment with vonoprazan monotherapy and vonoprazan and acotiamide combination therapy significantly improved FD symptoms. There were no significant differences in OTE between patients treated with vonoprazan monotherapy (42.9%) and those treated with vonoprazan and acotiamide combination therapy (52%). There were no significant differences in duodenal eosinophilic infiltration between the improved and unimproved groups treated with vonoprazan alone and vonoprazan and acotiamide combination therapy, respectively. In contrast, there was a significant difference ( P = 0.004) in the ratio of pancreatic enzyme abnormalities between the improved and unimproved patients treated with vonoprazan monotherapy and those treated with vonoprazan and acotiamide combination therapy., Conclusions: Long-term vonoprazan alone or vonoprazan and acotiamide combination therapy significantly improved each FD symptom. The OTE in patients treated with vonoprazan alone or vonoprazan and acotiamide combination therapy was only 50%. Long-term vonoprazan and acotiamide combination therapy may differentiate patients with pancreatic enzyme abnormalities from those with FD., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Review Committee of the Nippon Medical School Hospital issued approval 758-5-68. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nakamura et al.)

Objectives: Pancreatic fibrosis is one of the main pathological features of chronic pancreatitis (CP), suggesting a strong relationship between CP and pancreatic ductal cancer. There was no available data about pancreatic fibrosis and pancreatic dysfunction in the early CP (ECP) using endosonography (EUS)., Methods: Asymptomatic patients with pancreatic enzyme abnormalities (AP-P; n = 56) and patients with ECP ( n = 21) were determined by the absence of abnormal findings on upper gastrointestinal endoscopy, abdominal ultrasonography, and abdominal computed tomography. An Olympus EUS (GF-UCT 260; Olympus) was used to perform EUS. Open software "Image J", developed by NIH, was used to measure the surface area fraction of the designated elastic blue region. The maximum value among the pancreatic head, pancreatic body, and pancreatic tail was defined as the ELST-blue score. The exocrine and endocrine pancreatic functions were evaluated using the N -benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test and homeostasis model assessment of β-cell function (HOMA-β) value, respectively., Results: EUS score, lobularity, and hyperechoic foci/strands in patients with ECP were significantly ( p < 0.001) higher than those in patients with AP-P. In addition, there were no significant differences in the BT-PABA test (73.1 ± 25.5, 68.5 ± 15.6) and HOMA-β (93.1 ± 67.4, 73.5 ± 139.7) between patients with ECP and AP-P. The ELST-blue score measured by image J as the quantification tool in EUS strain elastography in patients with ECP was significantly higher ( p = 0.002) than that in patients with AP-P. Interestingly, the ELST-blue score was significantly associated with HOMA-β in patients with ECP., Conclusions: The ELST-blue score may be a useful tool for the evaluation of endocrine pancreatic dysfunction in the ECP., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background and Aim: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP)., Methods: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods., Results: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis., Conclusions: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group., Methods: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining., Results: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone., Conclusions: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis., Methods: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA)., Results: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups., Conclusions: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor., Methods: Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated., Results: There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients., Conclusions: Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P., Competing Interests: The authors have declared that no competing interest exist. I have read the journal’s policy and the authors of this manuscript have the following competing interests.

Background and Aim: Gastric atrophy is a precancerous lesion. We aimed to clarify whether gastric atrophy determined by artificial intelligence (AI) correlates with the diagnosis made by expert endoscopists using several endoscopic classifications, the Operative Link on Gastritis Assessment (OLGA) classification based on histological findings, and genotypes associated with gastric atrophy and cancer., Methods: Two hundred seventy Helicobacter pylori -positive outpatients were enrolled. All patients' endoscopy data were retrospectively evaluated based on the Kimura-Takemoto, modified Kyoto, and OLGA classifications. The AI-trained neural network generated a continuous number between 0 and 1 for gastric atrophy. Nucleotide variance of some candidate genes was confirmed or selectively assessed for a variety of genotypes, including the COX-2 1195, IL-1β 511, and mPGES-1 genotypes., Results: There were significant correlations between determinations of gastric atrophy by AI and by expert endoscopists using not only the Kimura-Takemoto classification ( P  < 0.001), but also the modified Kyoto classification ( P  = 0.046 and P  < 0.001 for the two criteria). Moreover, there was a significant correlation with the OLGA classification ( P  = 0.009). Nucleotide variance of the COX-2 , IL-1β , and mPGES-1 genes was not significantly associated with gastric atrophy determined by AI. The area under the curve values of the combinations of AI and the modified Kyoto classification (0.746) and AI and the OLGA classification (0.675) were higher than in AI alone (0.665)., Conclusion: Combinations of AI and the modified Kyoto classification or of AI and the OLGA classification could be useful tools for evaluating gastric atrophy in patients with H . pylori infection as the risk of gastric cancer., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan., Methods: One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively., Results: There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan., Conclusions: Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We have reported that refractory functional dyspepsia patients with pancreatic enzyme abnormalities (FD-P). We tried to analyze the prevalence of exocrine pancreatic insufficiency (EPI) in FD-P patients to clarify whether the pathophysiology of FD patients including clinical symptoms and quality of life were associated with EPI. We enrolled forty-nine patients presenting with typical symptoms of FD-P patients ( n  = 20) and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) ( n  = 29). Five pancreatic enzymes (p-amylase, lipase, elastase-1, trypsin, and PLA2) were measured and STAI-state/-trait and SF-8 were evaluated. Pancreatic exocrine function was analyzed using N -benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). There were no significant differences in patient background between FD-P and AP-P patients. BT-PABA test scores for FD-P patients (61.67 ± 5.55) were significantly ( p  = 0.01) lower than in AP-P patients (95.38 ± 2.36). Physical component scale (PCS) in FD-P patients was significantly ( p  = 0.002) lower than that in AP-P patients. STAI-state was relatively ( p  = 0.054) associated with BT-PABA test in FD-P and AP-P patients by multiple logistic regression analysis. The prevalence of EPI in FD-P patients was significantly higher than that in AP-P patients and was relatively associated with state of anxiety. Further studies will be needed to clarify how EPI or pancreatic enzyme abnormalities are associated with the pathophysiology of FD-P patients., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Background and Aim: Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN)., Methods: We compared the accuracy of physician-performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)-based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR-148a, miR-124a-3, NKX6-1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty-two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions., Results: The board-certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588)., Conclusion: AI with miR148s DNA methylation-based diagnosis is a potential modality for diagnosing GIN., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Since there were no available data about colonic diverticular bleeding in extremely elderly patients (>80 years old) treated with direct oral anticoagulants (DOACs), we tried to determine clinical characteristics in those with colonic diverticular bleeding taking DOACs and to compare clinical outcomes of those in DOAC-treated to those in warfarin-treated . We enrolled DOAC-treated ( n  = 20) and warfarin-treated ( n  = 23) extremely elderly patients with diverticular bleeding diagnosed by colonoscopy. We performed a retrospective review of patients' medical charts and endoscopic findings. We classified colonic diverticular bleeding based on endoscopic features due to modified previous study following three groups, type A (active bleeding), type B (non-active bleeding) and type C (bleeding suspected). Clinical outcomes such as number of recurrent bleeding, thrombotic events and mortality were estimated. There were no differences in endoscopical features and clinical characteristics between patients treated with DOAC and warfarin therapy. However, the number of recurrent bleeding, frequency of required blood transfusions and units of blood transfusion in warfarin-treated patients were significantly higher ( p <0.05) compared to those in DOAC-treated groups. In addition, mortality and thrombotic events did not differ between DOAC- and warfarin-treated patients. Clinical outcomes suggest that DOACs can be recommended for extremely elderly patients with colonic diverticular disease., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2021 JCBN.)

Background: To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model., Methods: Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue., Key Results: Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells., Conclusions and Inferences: Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them., (© 2020 John Wiley & Sons Ltd.)

Functional dyspepsia (FD) is a common disease that can markedly impair quality of life. In the 2016 Rome IV criteria, a diagnosis of FD requires the presence of bothersome FD symptoms. In 2009, a new diagnosis, early chronic pancreatitis (ECP), was proposed as a means to facilitate early treatment of chronic pancreatitis and prevent progression to chronic pancreatitis. Although chronic pancreatitis was reported to be a cause of dyspepsia, data on the relation between ECP and FD patients are limited. We therefore investigated differences between ECP patients and FD patients in the percentages of those with severe epigastric pain, early satiety, and postprandial abdominal fullness. Several studies reported an association between the cause of chronic pancreatitis and endosonographic features. In addition, endosonography was useful for distinguishing ECP patients from FD patients with pancreatic enzyme abnormalities. Thus, we compared endosonographic characteristics in these patient groups. Future studies should attempt to determine why selected FD patients with pancreatic enzyme abnormalities develop ECP.

Background: In our previous study, a single auricular application of capsaicin ointment, but not placebo improved cough reflex in elderly patients with dysphagia. Aims/Objectives: In the present study, we examined whether daily auricular application of capsaicin ointment continued to improve cough reflex in similar patients. Material and methods: With a cotton swab, 0.025% capsaicin ointment was applied in each external auditory canal alternately once a day for 2 weeks. The cough reflex sensitivity was evaluated on videoendoscopy using a numerical score and inhalation cough challenge test using citric acid in elderly dysphagic inpatients. Results: After daily auricular application of capsaicin ointment for 2 weeks, the endoscopic score of glottal closure and cough reflexes significantly improved, and the citric acid cough threshold significantly decreased. There was a significant correlation between the endoscopic score and the citric acid cough threshold before and after daily capsaicin application in the patients. Conclusions : Daily auricular stimulation with capsaicin ointment for 2 weeks continued to improve the cough reflex sensitivity in elderly patients with dysphagia. Significance: Daily auricular stimulation with capsaicin ointment would be a safe and effective intervention to prevent pneumonia in elderly with a risk of aspiration.

Background and Aims: To determine whether serum acylated ghrelin levels were associated with anxiety, clinical symptoms, depressive status, quality of life, gastric motility and endoscopic findings based on Kyoto classification in functional dyspepsia (FD) patients., Methods: We enrolled three groups, FD patients ( n  = 15) with high levels of acylated ghrelin, FD patients ( n  = 33) with normal levels of acylated ghrelin and FD patients ( n  = 35) with low levels of acylated ghrelin. There was no significant differences in the positivity of Helicobacter pylori infection among the three groups. Clinical symptoms were evaluated by Gastrointestinal Symptom Rating Scale (GSRS) and FD symptoms based on Rome III classification. Acylated ghrelin levels were measured by ELISA methods. Depressive status, anxiety, sleep disturbance were respectively asscessed by Self-rating questionnaire for depression (SRQ-D) score, STAI-state/-trait, Pittsburgh sleep quality index (PSQI) scores. Endoscopic findings were evaluated based on Kyoto classification., Results: Body Mass Index (BMI) in FD patients with low levels of acylated ghrelin was significantly higher ( p <0.001 and p  = 0.008, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. SRQ-D scores in FD patients with low levels of acylated ghrelin was significantly lower ( p  = 0.008 and p <0.001, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. Scoring of gastric atrophy, intestinal metaplasia, xanthoma and mucus based on Kyoto classification in FD patients with low levels of acylated ghrelin were significantly higher ( p <0.001, p  = 0.0077, p  = 0.036 and p  = 0.0063, respectively) compared to those in FD patients with more than low levels of acylated ghrelin., Conclusion: Acylated ghrelin levels were associated with BMI, depressive status, and endoscopic findings based on Kyoto classification in FD patients.

Background/aims: The aims of the study are to clarify the pathophysiological differences among early chronic pancreatitis (ECP), functional dyspepsia with pancreatic (FD-P) enzyme abnormalities and FD patients and to determine whether camostat mesilate, pancrelipase, and rabeprazole triple therapy improve FD symptoms in the ECP patients and FD-P patients in cross-over way., Methods: We enrolled 84 consecutive patients presenting with typical symptoms of FD patients (n = 42), ECP patients (n = 15), and FD-P patients (n = 27). Gastric emptying was assessed by the 13C-acetate breath test. ECP was diagnosed based on the criteria recommended by the Japan Pancreatic Association., Results: The proportions of female in ECP patients and FD-P were significantly higher compared to that in FD patients. The early phase of gastric emptying in ECP and FD-P patients was significantly disturbed compared to that in FD patients. The primary outcome of this study is that 4 weeks of camostat mesilate, pancrelipase, and rabeprazole triple therapy significantly ameliorated epigastric pain in ECP patients compared to acotiamide and rabeprazole combination therapy., Conclusion: Although there were no significant differences in pathophysiology between ECP patients and FD-P patients, triple therapy can significantly ameliorate epigastric pain in ECP patients. Further studies will be needed to clarify why triple therapy can improve epigastric pain in ECP patients., (© 2018 S. Karger AG, Basel.)

Background: There was no available data concerning the clinical differentiation between the updated definition of early chronic pancreatitis (ECP) and anti-acid therapy-resistant functional dyspepsia (RFD)., Aims: We aimed to determine whether clinical symptoms, gastric motility, psychogenic factors and fat intake can help distinguish early chronic pancreatitis (ECP) from anti-acid therapy-resistant functional dyspepsia patients with pancreatic enzyme abnormalities (RFD-P) and anti-acid therapy-resistant functional dyspepsia (RFD) patients using endosonography., Methods: We enrolled 102 consecutive patients presenting with typical symptoms of RFD patients (n = 52), ECP patients (n = 25) and RFD-P patients (n = 25). ECP patients were diagnosed based on the criteria recommended by the Japan Pancreatic Association. Gastric motility was evaluated by 13C-acetate breath tests. Severity of duodenal inflammation was examined., Results: 24.5% of RFD patients were determined as ECP using endosonography. Abdominal pain score in Gastrointestinal Symptom Rating Scale (GSRS) in the patients with ECP was significantly lower compared to that in the patients with RFD-P. There were no significant differences in State-Trait Inventory (STAI)-state/-trait scores, Self-Rating Questionnaire for Depression (SRQ-D) scores and clinical symptoms for fat intake among three groups. The early phase of gastric emptying (AUC5; AUC15) in ECP and RFD-P patients were significantly disturbed compared to those in RFD patients., Conclusions: Evaluation of severity of abdominal pain and measurement of the early phase of gastric emptying will be useful tools to distinguish ECP patients from RFD patients. Accurate diagnosis of ECP patients may contribute to the prevention from advancing of chronic pancreatitis., Competing Interests: The authors have declared that no competing interests exist.

A 56-year-old man was diagnosed with advanced adenocarcinoma of the esophagogastric junction. He received 1 course of neoadjuvant chemotherapy with S-1. After neoadjuvant chemotherapy, the primary tumor showed a remarkable decrease in size. Subtotalesophagectomy, D2 lymph node dissection, and reconstruction with a gastric tube through the posterior mediastinal route were performed. Pathological examination showed that most of the cancer cells had been destroyed, with a part where adenocarcinoma mucosa was seen. We successfully treated a case of advanced adenocarcinoma of the esophagogastric junction, with neoadjuvant S-1 chemotherapy and surgicalresection.

Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS. A previous study has reported that proton pump inhibitors (PPIs) and H 2 -blockers were equally effective in functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and cholinesterase inhibitor, has been shown to improve gastric motility in rodents and dogs, and to reduce PDS symptoms in patients in double-blind multicenter studies. The pharmacological mechanisms of acotiamide remain unknown; whether acotiamide alters gastric emptying and gastric accommodation in patients with functional dyspepsia remains an open question. Other emerging treatment options include Rikkunshito, a herbal medicine that improves gastric emptying through 5-hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic antidepressants (TCAs). Different drugs are needed to accommodate the clinical symptoms and etiology in individual patients., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There was not available data about the overlap between functional dyspepsia (FD) and pancreatic diseases. We aimed to determine whether epigastric pain syndrome (EPS) accompanying with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by Japan Pancreas Society (JPS) using endosonography. We enrolled 99 consecutive patients presenting with typical symptoms of FD, including patients with postprandial distress syndrome (PDS) ( n  = 59), EPS with pancreatic enzyme abnormalities ( n  = 41) and EPS without pancreatic enzyme abnormalities ( n  = 42) based on Rome III criteria. Gastric motility was evaluated using the 13 C-acetate breath test. Early chronic pancreatitis was detected by endosonography and graded from 0 to 7. The ratio of female patients among EPS patients (34/41) with pancreatic enzyme abnormalities was significantly ( p  = 0.0018) higher than the ratio of female EPS patients (20/42) without it. Postprandial abdominal distention and physical component summary (PCS) scores in EPS patients with pancreatic enzyme abnormalities were significantly disturbed compared to those in EPS patients without it. Interestingly, AUC 5 and AUC 15 values (24.85 ± 1.31 and 56.11 ± 2.51, respectively) in EPS patients with pancreatic enzyme abnormalities were also significantly ( p  = 0.002 and p  = 0.001, respectively) increased compared to those (19.75 ± 1.01 and 47.02 ± 1.99, respectively) in EPS patients without it. Overall, 64% of EPS patients with pancreatic enzyme abnormalities were diagnosed by endosonography as having concomitant early chronic pancreatitis proposed by JPS. Further studies are warranted to clarify how EPS patients with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by JPS.

Purple yam (Dioscorea alata L.), which is widely distributed in tropical and subtropical regions, is characterized by its color and viscosity. Previous studies have shown that purple yams contain a variety of acylated anthocyanins that exhibit higher levels of antioxidant activity than the corresponding nonacylated compounds. In this study, the pigments found in purple yams from the Philippines (D. alata) were isolated and evaluated in terms of antioxidant activity. Four new acylated anthocyanins, alanins (1-4) were isolated from the MeOH extracts of purple yam, which were subsequently determined to be cyanidin (1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins (5-8). The structures of 1-4 were determined by spectroscopic methods, including NMR and MS analyses. The antioxidant activities of anthocyanins 1-8 were investigated using oxygen radical absorbing capacity and ferric reducing antioxidant power assays.

Treatment with bevacizumab, an antiangiogenic agent, in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan. Bevacizumab improves the survival of patients with metastatic colorectal cancer; however, it may lead to complications such as bleeding, which are sometimes fatal. Bevacizumab should be administered only after careful consideration because the potential risks of therapy outweigh its benefits. Therefore, pharmaceutical companies do not recommend bevacizumab therapy for patients with brain metastases. While some reports support the cautious use of bevacizumab, others report that it is not always necessary to prohibit its use in patients with metastases to the central nervous system (CNS), including the brain. Thus, bevacizumab therapy in colorectal cancer patients with brain metastases is controversial, and it is unclear whether brain metastases are a risk factor for intracranial hemorrhage during anti-vascular endothelial growth factor (VEGF) therapy. We report a 64-year-old man and a 65-year-old man with recurrent colorectal cancer without brain metastases; these patients developed multifocal and solitary intracranial hemorrhage, respectively, after the administration of bevacizumab. Our findings suggest that intracranial hemorrhage can occur even if the patient does not have brain metastases prior to bevacizumab treatment and also suggest that brain metastases are not a risk factor for intracranial hemorrhage with bevacizumab treatment. These findings also question the necessity of excluding patients with brain metastases from clinical trials on anti-VEGF therapy.

A detailed analysis of the antioxidative activity of 12 carbohydrates including chondroitin sulfate, fucoidan, agaro-oligosaccharide, 2-deoxy-scyllo-inosose (DOI), Galbeta1-4DOI, D-glucuronic acid, chitobiose, D-mannosamine, D-galactosamine, D-glucosamine, heparin, and colominic acid was performed using four established methods: 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, superoxide dismutase (SOD) activity assay, and the deoxyribose method. Ascorbic acid and/or catechin were used as positive standards. In the DPPH radical scavenging activity measurements, fucoidan, DOI, and Galbeta1-4DOI showed remarkable levels of activity, although at lower levels than ascorbic acid. The SOD assay revealed that DOI, Galbeta1-4DOI, and agaro-oligosaccharide had high antioxidant activity, with DOI and Galbeta1-4DOI notably showing almost half of the antioxidative potency of ascorbic acid. Using the deoxyribose method, chitobiose and heparin showed the highest hydroxyl radical scavenging activity, followed by chondroitin sulfate, colominic acid, Galbeta1-4DOI, and d-glucosamine. Given that 11 of the carbohydrates analyzed share a common structure, agaro-oligosaccharide being the exception, we propose from our current results that at least one amino, carboxyl, carbonyl, or sulfonyl group is required, but is not in itself sufficient, for carbohydrates to function as antioxidants.

The diagnosis-related-group/prospective-payment system (DRG/PPS) was introduced into the health care system of the United States in 1983. This system triggered the development and implementation of clinical pathways aimed at reducing the length and cost of hospitalization. In Japan, trial use of a Japanese version of DRG/PPS was initiated in November 1998 in 10 hospitals under the control of the Ministry of Health and Welfare, and full-scale implementation of the system is expected in the near future. Clinical pathways, therefore, are a current focus of attention, mainly because of their success in enhancing management efficiency in the U.S. However, in actual clinical settings where clinical pathways are used, several Japanese health care providers have come to realize that they are also useful in improving staff coordination, patient satisfaction, and patient care, rather than simply reducing the length of hospital stay and cost of health care. The introduction of clinical pathways requires that treatment of the disease in question be defined and standardized. The implementation of pathways for the treatment of cancer, however, might prove difficult because of the high frequency of variation. In our experience, the main reason for the use of clinical pathways is not to reduce the number of variant cases but to provide high-quality care through the promotion of a team approach to treatment and enhanced patient care. Therefore, even if there were frequent variances following surgery for cancer, those occurring in accordance with the pathophysiological state of the patient would not interfere with management by clinical pathways. Clinical pathways are advantageous because they allow patients to know their treatment schedule; to prepare for hospitalization procedures; to have a better perspective on discharge; to reduce anxiety regarding hospital admission, even if it is the first time; to communicate better with doctors, nurses, and other medical care staff, leading to greater trust; and to improve their ability for self-management. These features are all important for the improvement of patient care. Furthermore, clinical pathways may lead to a situation in which the cost of hospitalization can be predicted prior to admission, enabling patients to compare differences between several hospitals. From our experience with gastric cancer, breast cancer, and esophageal cancer management, we consider clinical pathways to be of great benefit in helping to reform the current medical care system in regard to the management of cancer patients as well as patients with other diseases.

The first clinical application of biochemical modulation (BCM) of 5-fluorouracil (5-FU) was the sequential MTX/5-FU regimen proposed in 1977 by Bertino for the treatment of colorectal cancer. In Japan, sequential MTX/5-FU therapy was mainly used as a new method of treating gastric cancer, and attracted a great deal of attention because it proved effective in many cases of advanced gastric cancer that had been unresponsive to the previous chemotherapy, particularly scirrhous gastric cancer with poor prognosis. Its therapeutic efficacy varied according to histologic type, it was effective in cases of peritoneal dissemination and disseminated intravascular coagulopathy (DIC), it was associated with fewer adverse effects, and it was a multidrug chemotherapy based on a clear rationale. With sequential MTX/5-FU therapy as a starting point, fundamental studies of BCM and its clinical applications have expanded rapidly in Japan. This paper provides an outline of sequential MTX/5-FU therapy from the aspects of its mechanism of action, indications, therapeutic efficacy, relevance to adjuvant therapy, counter-measures to adverse effects, and emergence of resistance to the drugs involved. The high therapeutic efficacy of this therapy in certain histologic types is also discussed, and its combined use with other forms of BCM, as in triple BCM (LV/5-FU + CDDP/5-FU + MTX/5-FU), is introduced.

Dense distribution of varicose fibres containing neuropeptide Y-like immunoreactivity (NPY-LI) was found in the atrioventricular valves of the Japanese monkey, and moderately in the rat. The immunoelectron microscopy using immunogolds resulted in the localization of NPY-LI within the dense-cored vesicles which existed with the small clear vesicles in the unmyelinated axons near the endocardium. These NPY-LI-containing fibres may participate in regulation of vasomotor role or other functions of the atrioventricular valves.

A total of 222 surveillance colonoscopies were performed in 84 patients with ulcerative colitis between 1979-1989. In 60 patients with total colitis, 3 carcinomas, 2 high-grade, 4 low-grade and 8 indefinite for dysplasia were found. In 24 with left-sided colitis, 1 low-grade and 1 indefinite for dysplasia were found. The overall incidence of dysplasia in patients with total colitis was 28%, similar to the reported incidence from the Western countries. A sequence of dysplasia development was recorded in 14 cases. Progression of dysplasia was found in some of the low-grade or indefinite cases, however regression was also recorded in another cases. These results suggest the usefulness of surveillance colonoscopy for early detection of carcinoma in long-standing ulcerative colitis.