Prognostic value of moderate or massive ascites in patients with advanced gastric cancer.

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer.

Efficacy of Glycicumarin and Isoliquiritigenin in Suppressing Colonic Peristalsis in Both an Animal Model and a Clinical Trial.

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.

D-alanine Inhibits Murine Intestinal Inflammation by Suppressing IL-12 and IL-23 Production in Macrophages.

BACKGROUND AND AIMS: Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. METHODS: We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 days [d], acute colitis was induced using dextran sulphate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulphate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time polymerase chain reaction [PCR]. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. RESULTS: Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulphate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro, and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. CONCLUSIONS: Our results suggest that D-alanine prevents dextran sulphate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery for superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.

Conventional versus underwater endoscopic resection for superficial non-ampullary duodenal epithelial tumours.

BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

A new endoscopic scoring system corresponding to histological healing using linked color imaging in ulcerative colitis: the SOUL study.

Background and study aims An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0-2), area of inflammation (A) (Grade 0-3), and lymphoid follicles (L) (Grade 0-3). Histological healing was defined as Geboes score < 2B.1. Endoscopic and histopathological scores were determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R ( P  = 0.013) and A ( P  = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

Serum titer of neutralizing antibodies after COVID-19 vaccination in Japanese patients with inflammatory bowel disease.

Vaccination is an important strategy to reduce the infection rate and adverse events of coronavirus disease 2019 (COVID-19). However, the effect of COVID-19 vaccination for Japanese patients with inflammatory bowel disease (IBD) has not been fully elucidated. In the present study, we investigated the serum titer of neutralizing antibodies after COVID-19 vaccination in patients with IBD, treated with and without immunosuppressive therapy. The study consisted of 108 patients with IBD [76 with ulcerative colitis (UC) and 32 with Crohn's disease (CD)] from the gastroenterology outpatient clinic at the Hospital of the Kyoto Prefectural University of Medicine who underwent anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The control group included 64 healthy subjects who received the anti-SARS-CoV-2 vaccine. When 10 AU/ml of neutralizing antibodies was used as cut-off value, the positive rates of neutralizing antibodies of patients with UC, patients with DC, and the control group were 97.3%, 84.3%, and 100%, respectively. The neutralizing antibody titer showed no difference between patients treated with and without immunosuppressive therapy. These results indicate that COVID-19 vaccination may be useful in patients with IBD, treated with or without immunosuppressive therapy.

Partially hydrolyzed guar gum increased colonic mucus layer in mice via succinate-mediated MUC2 production.

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Evaluation of Environmental Stability and Disinfectant Effectiveness for Human Coronavirus OC43 on Human Skin Surface.

The environmental stability of human coronavirus OC43 (HCoV-OC43) on the surface of human skin and the effectiveness of disinfectant against HCoV-OC43, which are important to prevent contact transmission, have not been clarified in previous studies. Using previously generated models, we evaluated HCoV-OC43 stability and disinfection effectiveness. Then we compared the results with those for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median survival time of HCoV-OC43 on the surface of human skin was 24.6 h (95% confidence interval, 19.7 to 29.6 h), which was higher than that of SARS-CoV-2 (10.8 h). Although the in vitro disinfectant effectiveness evaluation showed that HCoV-OC43 has a higher ethanol resistance than SARS-CoV-2, HCoV-OC43 on the skin surface was completely inactivated by a minimum of 50% ethanol within 5 s (the log reduction values were >4.0). Moreover, 1.0% chlorhexidine gluconate and 0.2% benzalkonium chloride showed relatively high disinfectant effectiveness, and the log reduction values when these disinfectants were applied for 15 s were >3.0. HCoV-OC43 is highly stable on the skin surface, which may increase the risk of contact transmission. Although HCoV-OC43 has relatively high ethanol resistance, appropriate hand hygiene practices with current alcohol-based disinfectants sufficiently reduce the risk of contact transmission. IMPORTANCE This study revealed the environmental stability of HCoV-OC43 and disinfectant effectiveness against HCoV-OC43, which had not been demonstrated in previous studies. HCoV-OC43 is highly stable on the surface of human skin, with a survival time of approximately 25 h. High stability of HCoV-OC43 may increase the risk of contact transmission. Furthermore, the in vitro disinfectant effectiveness evaluation showed that HCoV-OC43, which is classified as an envelope virus, has a relatively high ethanol resistance. This finding suggests that disinfectant effectiveness may vary greatly depending on the virus and that each virus targeted for infection control should be evaluated individually. HCoV-OC43 on the skin surface was rapidly inactivated by 50% ethanol, which suggests that appropriate hand hygiene practices with current alcohol-based disinfectants can sufficiently reduce the risk of HCoV-OC43 contact transmission.

Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota.

Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 µmol/g vs. 103.9 µmol/g; p=0.015) and butyric acid (13.4 µmol/g vs. 39.2 µmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Obscure gastrointestinal bleeding from a large jejunal lipoma treated using an endoscopic unroofing technique with double balloon enteroscopy: a case study.

Small intestinal lipomas are rare, but may cause obscure gastrointestinal bleeding. The endoscopic unroofing technique excises only the upper third of the lipoma and allows both histological confirmation and complete treatment with minimal risk of perforation. We present a rare case of obscure gastrointestinal bleeding caused by a jejunal lipoma. A 75-year-old man on antiplatelet therapy presented to our department with melena and anemia. Computed tomography revealed he had a 45-mm jejunal submucosal tumor with fat attenuation. Endoscopic resection using an endoscopic unroofing technique with double balloon enteroscopy was successfully performed. The tumor was confirmed to be a lipoma.

Effects of Smoking on the Gut Microbiota in Individuals with Type 2 Diabetes Mellitus.

Smoking affects eating habits; however, few studies on smoking and the gut microbiota have reported the effects of diet in detail. This cross-sectional study aimed to determine the association between smoking and the gut microbiota, considering the impact of smoking on dietary intake. Dietary habits and the composition of the gut microbiota were assessed in 195 men with type 2 diabetes (164 non-current smokers and 31 current smokers) using a brief self-administered diet history questionnaire and 16S ribosomal RNA gene sequencing of fecal samples. The data were compared according to the current smoking status of the participants. Current smokers had high alcohol and sugar/sweetener intake and low fruit intake. The proportion of the Coprococcus genus was higher among current smokers. Multiple regression analysis adjusted for current smoking, age, exercise habits, alcohol intake, sugar and sweetener intake, and fruit intake showed that smoking was associated with the proportion of the Coprococcus genus. Current smoking was associated with both dietary intake and composition of the gut microbiota. Although dietary intake should be considered when investigating the association between smoking and the gut microbiota, the results suggest that the direct effect of smoking is more significant.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model.

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion: For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model.

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20 µg/g b.w.) or a vehicle as a control for 5 days, and pegfilgrastim was administered subcutaneously at 1 µg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells.