Efficacy and safety of rifaximin in patients with chronic intestinal pseudo-obstruction: a randomized, double-blind, placebo-controlled, phase II-a exploratory trial.

Chronic intestinal pseudo-obstruction (CIPO) is a rare intractable disease with limited treatment options. Small intestinal bacterial overgrowth (SIBO) often co-occurs with several diseases, including CIPO. While rifaximin (RFX) is effective in treating SIBO, its efficacy for CIPO remains unclear. Here, we aimed to investigate the efficacy and safety of RFX in adult patients with CIPO. Twelve patients were randomly assigned to receive RFX (400 mg three times daily, n=8) or a placebo (PBO, n=4) for 4 weeks. The global symptom score for abdominal bloating (GSS-bloating) and an original whole gastrointestinal symptoms score (O-WGSS) were collected, and a glucose hydrogen breath test (GHBT) and abdominal computed tomography (CT) were performed. No significant differences were observed in the primary endpoint. GSS-bloating improved by 75% and 25% in the PBO and RFX groups, respectively, and O-WGSS improved by 25% in both groups. No significant differences were observed in secondary and other endpoints, including the SIBO eradication rate in the GHBT and small intestinal volume on CT. In a post hoc analysis of SIBO-positive patients with CIPO (4/4 and 4/8 in the PBO and RFX groups), SIBO was eradicated in 25% and 75% of the patients (PBO and RFX groups, respectively) at the end of treatment, indicating a high eradication rate in the RFX group. Furthermore, the small intestinal gas volume decreased in the RFX group, and no severe adverse events occurred. Although no significant improvements were observed in subjective indicators, RFX may be beneficial in alleviating SIBO and reducing the small intestinal gas volume in SIBO-positive patients with CIPO.

Natural History of Chronic Intestinal Pseudo-obstruction and Need for Palliative Care.

Background/Aims: Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients. Methods: From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course. Results: Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m2, 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care. Conclusion: CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.

Exploratory, multicenter, open-label study to evaluate the effects of linaclotide in patients with chronic constipation with an insufficient response to magnesium oxide: A study protocol.

Background: Chronic constipation leads to poor quality of life, and treatment remains unsatisfactory for patients. In Japan, magnesium oxide has been commonly used as the first choice of treatment for constipation; however, there are some cases of low satisfaction with magnesium oxide treatment. Linaclotide has recently been used to treat chronic constipation. In this study, we will examine whether linaclotide improves symptoms and quality of life in patients showing insufficient response to magnesium oxide. Methods: This is an exploratory multicenter open-label study. The target number of patients is 64: 32 patients with and 32 without abdominal symptoms. Patients with chronic idiopathic constipation or irritate bowel syndrome with constipation diagnosed according to the Rome-IV criteria are eligible. Patients prescribed 0.99-2 g/day of magnesium oxide for at least 4 weeks will be included. Those who consent to the study will continue taking magnesium oxide for 2-4 weeks, and defecation will be documented. Patients who meet the criteria will be prescribed linaclotide (0.5 mg) daily for 12 weeks. The primary endpoint is a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score after 12 weeks of treatment. Conclusion: This is the first study to investigate the usefulness of linaclotide as a second-line treatment for chronic constipation. We will test the efficacy of treatment of constipation in patients with inadequate response to magnesium oxide. Trial registration: This study is registered with the Japan Registry of Clinical Trials (jRCT, jRCTs031200048).

Leukotriene Receptor Antagonist Therapy for the Chemoprevention of Human Rectal Aberrant Crypt Foci: Nonrandomized, Open-Label, Controlled Trial.

Leukotriene receptor antagonists (LTRA) are widely used drugs for treating allergic asthma, and they have recently been suggested to have a suppressive effect on carcinogenesis and cancer cell proliferation. Aberrant crypt foci (ACF) are considered a reliable surrogate biomarker of colorectal cancer. This prospective study explored the chemopreventive effect of an LTRA on colonic ACF formation and the safety of the medicine in patients as a pilot trial leading to a colorectal cancer chemoprevention trial.This was a nonrandomized, open-label, controlled trial in patients with colorectal ACFs. The participants were allocated to LTRA or observation groups. Patients in the LTRA group received 10 mg of montelukast orally daily for 8 weeks. After the intervention, colonoscopy was performed to evaluate the changes in the number of ACFs.From November 2017 to March 2020, 40 patients were enrolled. The first 30 were assigned to the LTRA group, and the remaining 10 were assigned to the observation group. In the LTRA group, the mean change in the number of ACFs per patient at 8 weeks from baseline was -2.4 ± 2.2, while the mean change in the observation group was 0.4 ± 2.3 (P = 0.002). There were no severe adverse events.This is the first study to explore the effect of LTRAs against colorectal ACF formation in humans. LTRAs are potential candidates for chemoprevention in colorectal cancer. PREVENTION RELEVANCE: We conducted the first LTRA chemoprevention trial for human rectal ACFs, which is considered a surrogate marker of colorectal carcinogenesis. 8-week treatment with LTRA suppressed ACF formation and cell proliferation in colonic epithelium. LTRAs are possible candidates for chemoprevention in colorectal cancer. See related Spotlight, p. 637.

Rationale and design of a multicenter, single-group, open-label trial aiming at investigating the effectiveness of elobixibat for loss of defecation desire in patients with chronic constipation.

Background: Approximately 60% of patients with chronic constipation (CC) have a significantly higher rate of loss of defecation desire (LODD). Bile acids are expected to have a restorative effect on defecation desire (DD) because they lower the rectal sensory threshold, which is an objective index of DD. Elobixibat (EXB) specifically inhibits the ileal bile acid transporter/apical sodium-dependent bile acid transporter, which is a transporter involved in the reabsorption of bile acids in the terminal ileum. This study aims to investigate the LODD improvement rate in patients with CC after 4 weeks of EXB treatment. Methods: A total of 40 adult patients with CC who meet the eligibility criteria will be enrolled. Patients will receive oral EXB (10 mg/day) for 4 weeks. A patient diary will be provided daily at 4 weeks after treatment. The primary endpoint will be the percentage LODD improvement at week 4 of the treatment period from week 2 of the observation period using questionnaires. Ethics and dissemination: Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board prior to participant enrolment (approval number: CRB21-008). The results of this study will be submitted for publication in international peer-reviewed journals, and key findings will be presented at international scientific conferences. Participants desiring the results of this study will be directly contacted for data dissemination. Trial registration: This trial was registered at ClinicalTrials.gov (NCT05165199). Protocol version: 1.0, September 21, 2021.

Rationale and design of a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated trial to investigate the efficacy and safety of elobixibat for chronic constipation.

INTRODUCTION: Chronic constipation (CC) is a functional disorder that negatively impacts the quality of life of patients. This is a protocol for a multicentre, 12-week, randomised, double-blind, placebo-controlled study to test the efficacy and safety of elobixibat (EXB) versus placebo in patients with CC. METHODS AND ANALYSIS: This will be a multicentre, double-blind, placebo-control, randomised controlled trial. A total of 100 adult patients with CC, diagnosed based on Rome IV criteria, who fulfil the inclusion/exclusion criteria will be enrolled. The patients will be randomly assigned to receive EXB (10 mg) or placebo treatment (n=50 per group). Blood tests and stool sampling will be performed 12 weeks following initiation of treatment and questionnaires will be issued to participants. The primary outcome will be the change in complete spontaneous bowel movements after 12 weeks of administration. The secondary outcomes will include the change in Japanese Patient Assessment of Constipation Quality of Life and absolute serum and faecal bile acid. ETHICS AND DISSEMINATION: Ethics approval has been obtained from Yokohama City University Certified Institutional Review Board before participant enrolment. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. PROTOCOL VERSION: V.3.0, 15 June 2021. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (number NCT04784780).

Effectiveness of Naldemedine Compared with Magnesium Oxide in Preventing Opioid-Induced Constipation: A Randomized Controlled Trial.

Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO.

A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours.

Fusobacterium nucleatum is associated with the progression of colorectal cancer. Thus, the possibility of preventing colorectal cancer or its progression by targeting F. nucleatum has been explored. As F. nucleatum is associated with periodontitis, we analysed whether treating periodontitis could influence F. nucleatum abundance in the colon. Patients with colorectal tumours who underwent colonoscopy were recruited. Patients diagnosed with periodontitis by a dentist were treated for approximately 3 months. Endoscopic resection of colorectal tumours was performed after periodontitis treatment, and resected tumours were pathologically classified as high-(HGD) or low-grade dysplasia (LGD). Saliva and stool samples were collected before and after the treatment. Of the 58 patients with colorectal tumours, 31 were included in the study, 16 showed improvement in periodontitis, and 11 showed no improvement. Stool F. nucleatum levels before treatment were significantly lower in the LGD group than in the HGD group. A significant decrease in faecal F. nucleatum levels was observed in patients who underwent successful treatment but not in those whose treatment failed. Salivary F. nucleatum levels were not altered in patients despite periodontal treatment. Thus, successful periodontitis treatment reduces stool F. nucleatum levels and may aid research on periodontitis and suppression of colorectal cancer development.

Elobixibat Effectively Relieves Chronic Constipation in Patients with Cancer Regardless of the Amount of Food Intake.

BACKGROUND: Constipation is a common, distressing complication in patients with cancer receiving palliative care. Elobixibat is a novel inhibitor of the ileal bile acid transporter that is used to treat chronic constipation by stimulating bowel function. However, its efficacy in patients with cancer has not been examined. This study investigated the drug's effectiveness in patients with cancer with chronic constipation. PATIENTS AND METHODS: This prospective-sampling, single-center, observational study included hospitalized patients with cancer diagnosed, using the Rome IV criteria, with chronic constipation. Within 2 weeks of hospitalization, each participant was administered elobixibat (5-15 mg) daily until discharge. Spontaneous bowel movements (SBMs), complete spontaneous bowel movements (CSBMs), Bristol stool form scale (BSFS) scores, and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) scores were assessed before and after elobixibat administration. We also evaluated the relationship between the amount of food consumed and the SBM frequency. RESULTS: Among the 83 participants, the mean pre- and post-treatment frequencies of daily SBMs were 0.3 and 1.2 (p < .0001) and those of CSBMs were 0.1 and 0.6 (p < .0001), respectively. The mean pretreatment BSFS score was 1.6, whereas the post-treatment value was 3.5 (p < .0001); the mean PAC-QOL score (overall) improved from 1.01 to 0.74 (p = .01). There was no significant change in the daily SBM frequency between fasting and feeding states (1.2 vs. 1.3; p = .8), and there was no correlation between the amount of food intake and the SBM frequency after elobixibat administration (r = .03). Serious adverse events were not observed. CONCLUSION: This study showed that elobixibat is safe and effective for patients with cancer with chronic constipation, regardless of the food intake amount. IMPLICATIONS FOR PRACTICE: Elobixibat was effective at relieving chronic constipation in patients with various cancers. Serious adverse events were not observed, and the relief of constipation was independent of variation in food intake.

Efficacy of Bifidobacterium bifidum G9-1 in improving quality of life in patients with chronic constipation: a prospective intervention study.

Chronic constipation is a functional disorder that decreases a patient's quality of life (QOL). Because dysbiosis has been associated with constipation, we aimed to investigate the efficacy of Bifidobacterium bifidum G9-1 (BBG9-1) in improving QOL in patients with constipation. This was a prospective, single-center, non-blinded, single-arm feasibility trial. A total of 31 patients with constipation and decreased QOL received BBG9-1 treatment for 8 weeks, followed by a 2-week washout period. The primary endpoint was change in the overall Japanese version of the patient assessment of constipation of QOL (JPAC-QOL) score after probiotic administration relative to that at baseline. Secondary endpoints included changes in gut microbiota, stool consistency, frequency of bowel movement, degree of straining, sensation of incomplete evacuation, and frequency of rescue drug use. The overall JPAC-QOL scores and frequency of bowel movement significantly improved after BBG9-1 administration from those at baseline (p<0.01 and p<0.01, respectively). There were no statistically significant changes in other clinical symptoms. Subset analysis revealed that patients with initial Bristol Stool Form Scale stool types of <4 had improvements in stool consistency, a significant increase in the frequency of bowel movements, and a significant alleviation in the degree of straining, following BBG9-1 administration. At the genus and species levels, Sarcina and Sarcina maxima were significantly increased. Functional analysis showed that butanoate metabolism increased significantly, whereas methane metabolism decreased significantly. We concluded that BBG9-1 is safe and improves QOL in patients with constipation. The underlying improvements may be due to changes in stool consistency.

Efficacy of sedation with dexmedetomidine plus propofol during esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: During endoscopic submucosal dissection for superficial esophageal cancer, patient body movement can sometimes occur, which may cause discontinuation of the procedure. Propofol and dexmedetomidine have recently been found to be useful sedatives for endoscopic submucosal dissection. This study investigated whether sedation using propofol plus dexmedetomidine can suppress the patient's body movements during esophageal endoscopic submucosal dissection and compared this combination with sedation using propofol alone. METHODS: This was a prospective double-blind randomized controlled trial. Patients with superficial esophageal cancers who underwent esophageal endoscopic submucosal dissection at Yokohama City University Hospital were prospectively enrolled and were randomly assigned to the propofol and the propofol plus dexmedetomidine groups. The primary endpoint was the incidence of restlessness. The secondary endpoints were the satisfaction score, maintenance dose of propofol, and number of rescue propofol injections. RESULTS: Sixty-six patients (propofol group: n = 33; combination group: n = 33) were included. The combination group had a significantly lower incidence of restlessness than the propofol group (3.0% vs 27.3%, P = 0.02). In the combination group, the satisfaction scores of the endoscopists were significantly higher, the maintenance dose of propofol was significantly lower, and the number of rescue propofol injections was lower than those in the propofol group (3.0% vs 18.2%, P < 0.001). Although the incidence of bradycardia was significantly higher in the combination group (30.3% vs 3.0%, P < 0.01), no serious adverse effects occurred. CONCLUSION: The propofol plus dexmedetomidine combination provided excellent sedation that effectively suppressed the patient's body movements during esophageal endoscopic submucosal dissection.

Relationship between Stool Form and Quality of Life in Patients with Chronic Constipation: An Internet Questionnaire Survey.

INTRODUCTION: Chronic constipation (CC) is a highly prevalent functional bowel disorder with low treatment satisfaction and impaired quality of life (QOL). However, physicians tend to emphasize only "stool frequency," and relationship between "stool form" and QOL remains unclear. In this study, we aimed to investigate the actual situation of CC treatment in Japan and elucidate the relationship between stool form and QOL in patients with CC. METHODS: We conducted an online questionnaire survey in September 2018 targeting Japanese adult patients already diagnosed with CC and taking prescribed drugs. Assessments included the type of drug treatment, treatment duration, frequency of drug use, frequency of bowel movements (BMs), Bristol Stool Form Scale (BSFS), and Japanese version of the Patient Assessment of Constipation QOL (PAC-QOL) scores. Relationship between BSFS and Japanese PAC-QOL scores was analyzed, and most important factor that influences QOL was investigated. RESULTS: A total of 614 subjects were enrolled. Of these, 398 (64.8%) regularly used magnesium oxide and 162 (26.4%) used stimulant laxative, especially 81 (50.0%) used stimulant laxative "everyday." Mean score of the PAC-QOL was 1.29 ± 0.74, and the lowest score (highest QOL) of 0.94 ± 0.61 was observed in BSFS type 4. Significant difference was seen between BSFS type 4 and all the other types except type 7. Multivariate analysis revealed that normal stool form (BSFS type 4) and BMs ≥3/week are strongly related to decreases of PAC-COL score. In BSFS types 6 and 7, 36% of individuals experienced self-discontinuation of prescribed drugs and 53% self-reduced drug intake because of excessive effects. CONCLUSIONS: Stool form and frequency of BMs are relevant to QOL, especially normal stool form (BSFS type 4) is important for improving the QOL in patients with constipation. Physicians should focus on "stool form" and reconsider the prescription especially in BSFS types 6-7 patients.

The efficacy of aspirin and metformin combination therapy in patients with rectal aberrant crypt foci: a double-blinded randomized controlled trial.

BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) continue to increase worldwide. Therefore, new preventive strategies are needed to lower the burden of this disease. Previous studies reported that aspirin could suppress the development of sporadic colorectal adenoma. In addition, metformin is a biguanide derivative that is long widely used for the treatment of diabetes mellitus and has recently been suggested to have a suppressive effect on carcinogenesis and cancer cell growth. Both drugs exhibit a chemopreventive effect, but their efficacy is limited. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are more prevalent in patients with cancer and adenomas, and considered a reliable surrogate biomarker of CRC. Thus, we designed a prospective trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of aspirin combined with metformin on colorectal ACF formation in patients scheduled for polypectomy. METHODS: This study is a double-blind randomized controlled trial that will be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients will be recruited for the study and the number of ACF in the rectum will be counted at the baseline colonoscopy. Then, the participants will be allocated to one of the following two groups; the aspirin plus placebo group or the aspirin plus metformin group. Patients in the aspirin plus placebo group will receive oral aspirin (100 mg) and placebo for 8 weeks, and those in the aspirin plus metformin group will receive oral aspirin (100 mg) and metformin (250 mg) for 8 weeks. After 8 weeks of administration, polypectomy will be performed to evaluate changes in the number of ACF, and the cell-proliferative activity in the normal colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study proposed that will explore the effect of aspirin combined with metformin on the formation of colorectal ACF in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000028259 . Registered 17 July 2017.

The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. METHODS: This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. DISCUSSION: This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.

Difference in Defecation Desire Between Patients With and Without Chronic Constipation: A Large-Scale Internet Survey.

INTRODUCTION: Defecation desire (DD) is an important physiological component of normal defecation. However, knowledge of DD in the general population and in individuals with chronic constipation (CC) is lacking. We aimed to assess the prevalence of DD in the general population and individuals with CC and to understand the impact of treatment on DD among individuals with CC. METHODS: We conducted an online questionnaire survey targeting the Japanese general population in 2019. DD was reported as never, rarely, usually, or always. Individuals who self-reported constipation and met the Rome IV criteria for functional constipation but did not for irritable bowel syndrome were included in the CC group, while the same number of age-/sex-matched controls who met neither functional constipation nor irritable bowel syndrome criteria was included in the non-CC group. Individuals who reported DD as rarely or never were defined as having loss of DD (LODD). RESULTS: Of the 20,986 participants, 2,587 were included in the CC group (12.3%). LODD was significantly higher in the CC individuals than in the non-CC controls (57.4% vs 8.3%, respectively, P < 0.001, odds ratio 14.84 [95% confidence interval 12.65-17.42]). Satisfaction with treatment for constipation was lower in individuals with persistent LODD (25.9%) compared with those with improved LODD (56.5%) on treatment (P < 0.001, odds ratio 2.48 [1.39-4.43]). DISCUSSION: LODD is common in CC and is associated with decreased satisfaction to treatment. Greater attention should be paid to DD when treating patients with CC.

The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota.

BACKGROUND: Elobixibat, a novel inhibitor of apical sodium-dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function. AIMS: To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota. METHODS: This was a prospective, single-centre study. After baseline period, patients received 10 mg daily of elobixibat for 2 weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration. RESULTS: In the 30 patients analysed, the frequency of pre- and post-treatment bowel movements per fortnight was 7 and 10 (P < 0.001), respectively. The pre-treatment faecal bile acid concentration increased significantly from 10.9 to 15.0 µg/g stool post-treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94 µg/g stool to post-treatment 5.02 µg/g stool, P = 0.036) and in glycine-conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels. CONCLUSIONS: Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.

The protective effect of Bifidobacterium bifidum G9-1 against mucus degradation by Akkermansia muciniphila following small intestine injury caused by a proton pump inhibitor and aspirin.

BACKGROUND: Proton pump inhibitors (PPIs) can alleviate upper gastrointestinal injury but paradoxically exacerbate aspirin (ASA)-induced small intestine injury. In this study, our goal was to simulate this exacerbation by developing an appropriate animal model, which may help in establishing treatments. Methods: Male mice were fed a 60% fructose diet for 9 weeks, then administered 200 mg/kg ASA 3 h before sacrifice. The PPI omeprazole was administered intraperitoneally once daily for 9 weeks. Bifidobacterium bifidum G9-1 was administered orally for the last week. In addition, Akkermansia muciniphila was administered orally for 9 weeks instead of omeprazole. Results: ASA-induced small-intestine injury was observed in high-fructose fed mice. Omeprazole exacerbated ASA-induced intestinal damage, significantly decreased Bifidobacteria levels, and significantly increased A. muciniphila counts in the jejunum. The direct administration of A. muciniphila caused thinning of the jejunum mucus layer, which was also observed in mice that received ASA and omeprazole. On the other hand, the administration of Bifidobacterium bifidum G9-1 inhibited A. muciniphila growth and reduced thinning of the mucus layer. The number of goblet cells in the jejunum was reduced by the administration of ASA and omeprazole, while Bifidobacterium bifidum G9-1 prevented the reduction. Conclusions: These results suggest that omeprazole-induced gut dysbiosis promotes Akkermansia growth and inhibits Bifidobacterium growth, leading to a thinning of the mucus layer through a reduction in goblet cells in the small intestine. Probiotics are, therefore, a promising approach for the treatment of small intestine injury.

Clinical impact of evaluation of frailty in endoscopic submucosal dissection for early gastric cancer in elderly patients.

AIMS: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed safely and effectively in elderly patients; however, whether ESD for EGC in elderly patients with frailty is safe and improves prognosis remains unclear. METHODS: In total, 142 patients aged ≥80 years who underwent ESD for EGC between September 2008 and September 2014 were included. We compared outcomes between patients with frailty and those without frailty. Frailty was assessed using the Clinical Frailty Scale (CFS) based on a patient's status before admission. Study endpoints were short- and long-term clinical outcomes after ESD. RESULTS: Patients were allocated into two groups: no frailty (CFS 1-3, n = 101) versus frailty (CFS 4-7, n = 41). Short-term clinical outcomes, specifically, adverse events and curability, did not differ between the two groups. For the long-term clinical outcomes, patients with frailty had significantly worse outcomes after ESD than those without frailty (the 3-year overall survival rates were 73.2% vs. 93.1%; P < 0.001 with log-rank test). The Cox proportional hazards model showed that frailty was only an independent risk factor for poor prognosis. CONCLUSIONS: ESD for EGC is safe for elderly patients with or without frailty. However, elderly patients with frailty have a significantly poorer prognosis than those without frailty after ESD. Our results indicate that the frailty evaluation may be helpful to determine whether ESD for EGC should be performed. Geriatr Gerontol Int 2020; 20: 461-466.

Investigation of the Local Recurrence Rate after Colorectal Endoscopic Mucosal Resection: Is Incomplete Polyp Resection Really a Clinically Important Problem? Analysis of the Rationale for the "Resect and Discard" Strategy.

Background/Aims: The "Resect and Discard" strategy is a potentially useful strategy. At present, only the lesion size and accuracy of diagnosis are cited as considerations for clinical adoption of this strategy. On the other hand, histopathology of the resected specimens after Endoscopic Mucosal Resection (EMR) reveals often an unclear or positive-margin status, implying Incomplete Polyp Resection (IPR). If IPR indeed increased the risk of local recurrence, histopathological evaluation of the margin would be indispensable and clinical adoption of this strategy is difficult. The aim of this study is to verify the association between IPR and the risk of local recurrence. Methods: The 1872 polyps and 603 EMR cases in 597 patients who had EMR between May 2013 and May 2014 were enrolled. The local recurrence rate until 3 years after the EMR in cases with the target lesions of the "Resect and Discard" strategy was determined in the negative-margin and IPR groups. Results: The final analysis was performed using the data of 1092 polyps, and 222 were categorized into the IPR group. There were no cases of recurrence in either of the groups. Conclusion: This is the world's first report conducted to examine the correlation of IPR and the local recurrence rate for clinical practice of "Resect and Discard" strategy. There is the possibility that pathological evaluation of the margins after EMR in patients with small polyps can be skipped.

Assessment of colonic contents in patients with chronic constipation using MRI.

Although chronic constipation is common, colonic functional evaluating tests are uncommon. This study examines whether chronic constipation and gastrointestinal symptoms are correlated with the lateral diameter of the colon measured from MRI images. We included chronic constipation patients in a prospective, cross-sectional study using MRI at three centers. We divided 3D MRI colorectal images into 6 segments using with specified sequences and selected the maximum luminal diameter from each segment. We used the GSRS questionnaire to evaluate gastrointestinal symptoms. We evaluated the correlation between luminal diameters and GSRS scores. We found the following positive correlations: descending colon and unsatisfactory defecation symptoms; sigmoid colon and diarrhea; and rectum and constipation. The sum and ratio of the ascending and sigmoid colon diameters correlated with nausea and diarrhea. The sum of the transvers to the sigmoid colon diameter also correlated with nausea and diarrhea. The sum of all segment diameters correlated with nausea and constipation. In conclusion, we showed cross-sectional study of colonic MRI correlate with gastrointestinal symptoms. MRI might be useful for colonic motility evaluations to determine appropriate constipation treatments (Clinical trial registry number UMIN 000021274).