Current Treatment Practices for Adult Patients with Constipation in Japan.

BACKGROUND: The prevalence of constipation in Japan is estimated to be 2-5%. Constipation is a disease found in older adults. In particular, Japan is an aging society, with 65% of men and 80.5% of women aged 65 years or older accounting for the majority of its population. Chronic constipation may be associated with survival, cardiovascular events, decreased quality of life, and death. This study summarizes the recent findings regarding constipation treatment practice in Japan. SUMMARY: Until recently, the diagnosis of constipation was mainly based on medical interviews; however, with the recent development of handheld ultrasound devices, both physicians and nurses can easily and objectively diagnose fecal retention. Magnesium oxide and stimulant laxatives have been the mainstay treatments; however, since 2012, more than five new drugs for treating constipation have become available in Japan. KEY MESSAGES: Magnesium oxide is less effective in patients who use acid-secretion inhibitors and patients who have undergone total gastrectomy and should be cared for hypermagnesemia. In addition, regular use of stimulant laxatives may lead to colonic inertia and decreased bowel movements; therefore, they should be used only occasionally. The following is an overview of the different uses of conventional and newer laxatives for treating constipation.

Evidence-Based Clinical Guidelines for Chronic Constipation 2023.

The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.

Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and anti-diarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogs, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.

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 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.

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.

Continued Use of a Single Antiplatelet Agent Does Not Increase the Risk of Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: With the aging of the population and rising incidence of thromboembolic events, the usage of antiplatelet agents is also increasing. There are few reports yet on the management of antiplatelet agents for patients undergoing colorectal endoscopic submucosal dissection (ESD). AIMS: The aim of this study is to evaluate whether continued administration of antiplatelet agents is associated with an increased rate of delayed bleeding after colorectal ESD. METHODS: A total of 1022 colorectal neoplasms in 927 patients were dissected at Yokohama City University Hospital and its three affiliate hospitals between July 2012 and June 2017. We included the data of 919 lesions in the final analysis. The lesions were divided into three groups: the no-antiplatelet group (783 neoplasms), the withdrawal group (110 neoplasms), and the continuation group (26 neoplasms). RESULTS: Among the 919 lesions, bleeding events occurred in a total of 31 (3.37%). The rate of bleeding after ESD was 3.3% (26/783), 4.5% (5/110), and 0% (0/26), respectively. There were no significant differences in the rate of bleeding after ESD among the three groups (the withdrawal group vs. the no-antiplatelet group, the continuation group vs. the no-antiplatelet group, and the withdrawal group vs. the continuation group). CONCLUSIONS: Continued administration of antiplatelet agents is not associated with any increase in the risk of delayed bleeding after colorectal ESD. Prospective, randomized studies are necessary to determine whether treatment with antiplatelet agents must be interrupted prior to colorectal ESD in patients who are at a high risk of thromboembolic events.

Comparison of the early effects of vonoprazan, lansoprazole and famotidine on intragastric pH: a three-way crossover study.

To promote symptom relief from acid-related diseases, a medicine with a rapid-onset effect is ideal. The aim of this study was to investigate the early inhibitory effect on gastric acid secretion after a single oral administration of vonoprazan, which represents a new class of proton pump inhibitors, and to compare this effect with those of lansoprazole and famotidine. Ten Helicobacter pylori (HP)-negative male subjects participated in this randomized, three-way crossover study. A single oral administration of vonoprazan (20 mg), lansoprazole (30 mg) or famotidine (20 mg) was performed, and the intragastric pH was continuously monitored for 6 h. Each drug was administered at least seven days apart. The average intragastric pH during the 6-h period after the administration of famotidine was higher than that after the administration of lansoprazole (median: 4.45 vs 2.65; p = 0.0284). A similar result was observed for vonoprazan and lansoprazole (median: 4.30 vs 2.65; p = 0.0322). In conclusions, oral administration of vonoprazan and famotidine in HP-negative healthy male subjects caused the intragastric pH to rise more quickly than did lansoprazole. (Trial Registration: UMIN000020989).

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).

Clinical value of capsule endoscopy for detecting small bowel lesions in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: To evaluate the clinical value of capsule endoscopy (CE) in patients with intestinal Behçet's disease (BD). METHODS: The present study was a case-control pilot study conducted in intestinal BD patients and healthy volunteers. A total of 19 patients with intestinal BD (intestinal BD group) and 19 healthy volunteers (control group) matched for age and sex were enrolled. Frequency, number of small bowel lesions per subject, and Lewis score were comparatively evaluated between the two groups. RESULTS: Of the 19 patients with intestinal BD, 18 (94.7%) had reddened lesions, 15 (78.9%) had erosions, and nine (47.4%) had ulcers. There were significant differences in the frequency of reddened lesions (P < 0.0001), erosions (P < 0.0001) and ulcers (P = 0.0011) between the two groups. The difference in the number of small bowel lesions between the two groups was also statistically significant. The median Lewis score in the intestinal BD group was significantly higher than that in the control group (intestinal BD group 237 (0-768) vs. control group 8 (0-135); P < 0.0001). Analysis according to the location in the small bowel revealed that the frequency of ulcers tended to increase towards the distal intestine. CONCLUSION: This is the first CE study conducted to examine small bowel involvement in intestinal BD patients. Our results suggest that CE evaluation is necessary, in addition to colonoscopy, in all intestinal BD patients.

Feasibility of deep sedation with a combination of propofol and dexmedetomidine hydrochloride for esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: The aim of the present study was to evaluate the efficacy and safety of sedation with a combination of propofol (PF) and dexmedetomidine (DEX) compared with sedation with benzodiazepines in esophageal endoscopic submucosal dissection (ESD). METHODS: We retrospectively reviewed clinical data for 40 consecutive patients who had undergone esophageal ESD at the Yokohama City University Hospital between July 2012 and August 2014. Of these patients, 20 were sedated with benzodiazepines (conventional group) and another 20 patients were sedated with a combination of PF and DEX (combination group). Parameters for efficacy and safety of sedation were evaluated by comparisons between the two groups. RESULTS: Median procedural times in the combination group were shorter than those in the conventional group (61 min vs. 89 min, P = 0.03), and the percentage of patients who showed restlessness in the combination group was significantly lower than that in the conventional group (25% vs. 65%, P = 0.025). Incidences of hypotension and bradycardia in the combination group were higher than those in the conventional group (60% vs. 15%, P = 0.008, and 60% vs. 15%, P = 0.008, respectively). CONCLUSION: This retrospective study suggests that a combination of PF and DEX may provide stable deep sedation with less body movement than benzodiazepines during esophageal ESD.

[Chronic intestinal pseudo-obstruction].

Chronic intestinal pseudo-obstruction(CIPO) is a rare severe digestive disease in which clinical symptoms of intestinal obstruction appear without any mechanical cause. Pathophysiologically, CIPO shows ineffective intestinal propulsion due to an impairment of intestinal smooth muscle, enteric nervous system, and interstitial cells of Cajal(ICC). Sustained increased intra-bowel pressure often causes small intestinal malabsorption and bacterial translocation, and leads to malnutrition and blood stream infection (sepsis). Key points of the medical approach for CIPO are to improve nutritional status and reduce abdominal symptoms. Dietary cure and defecation control are the main options in mild cases, whereas home-parenteral-nutrition(HPN) and decompression therapy are often needed in severe cases. Stimulant laxatives, prokinetics and herbal medicine are usually used but often in fail. Percutaneous endoscopic gastrojejunostomy(PEG-J) tube may be burdenless compared to conventional ileus tube. Most important points in the management of this disease are to make a correct diagnosis as early as possible and avoid unnecessary surgery. However, no clear diagnostic criteria have been established so far. Manometry, scintigraphy, and full-thickness biopsy are the major examination for the CIPO diagnosis in the Western countries; however these specialized examinations are not popular in Japan. Therefore the Research Group(chief investigator, Atsushi Nakajima) proposed Japanese diagnostic criteria in 2009 to facilitate the diagnosis of this rare disease by the general physician. In 2013, we have reported that cine-MRI is a non-invasive diagnostic method for CIPO. Although further data are eagerly awaited, it can become a promising diagnostic tool in CIPO patients. Furthermore the Japanese criteria have been revised, and in 2014, the comprehensive criteria from a child to an adult have been devised. In 2015, CIPO is newly certified as Specified Rare and Intractable Disease which is subsidized from public expense, in Japan. In the future, the diagnostic criteria should be appropriately modified by consultation with additional researchers to make them more practical and internationally applicable.

Conditional knockout of the leptin receptor in the colonic epithelium revealed the local effects of leptin receptor signaling in the progression of colonic tumors in mice.

Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.

Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry.

BACKGROUND: To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients. OBJECTIVE: To investigate factors influencing the risk of small-bowel mucosal breaks in individuals taking continuous low-dose aspirin. DESIGN: Capsule endoscopy data were collected prospectively from 5 institutions. SETTING: Yokohama City University Hospital and 4 other hospitals. PATIENTS: A total of 205 patients receiving treatment with low-dose aspirin for over 3 months. INTERVENTIONS: Colonoscopic and upper GI endoscopy had been performed in all of the patients before the capsule endoscope evaluation. MAIN OUTCOME MEASUREMENTS: Risk factors for small-bowel mucosal breaks. RESULTS: Of the 198 patients (141 male; mean age 71.9 years) included in the final analysis, 114 (57.6%) had at least 1 mucosal break. Multivariate analysis identified protein pump inhibitor (PPI) use (OR 2.04; 95% confidence interval [CI], 1.05-3.97) and use of enteric-coated aspirin (OR 4.05; 95% CI, 1.49-11.0) as independent risk factors for the presence of mucosal breaks. LIMITATIONS: Cross-sectional study. CONCLUSION: PPI use appears to increase the risk of small-bowel injury in patients who take continuous low-dose aspirin. Clinicians should be aware of this effect of PPIs; new strategies are needed to treat aspirin-induced gastroenteropathy.

Frequency and risk factors for rebleeding events in patients with small bowel angioectasia.

BACKGROUND: Small bowel angioectasia is reported as the most common cause of bleeding in patients with obscure gastrointestinal bleeding. Although the safety and efficacy of endoscopic treatment have been demonstrated, rebleeding rates are relatively high. To establish therapeutic and follow-up guidelines, we investigated the long-term outcomes and clinical predictors of rebleeding in patients with small bowel angioectasia. METHODS: A total of 68 patients were retrospectively included in this study. All the patients had undergone CE examination, and subsequent control of bleeding, where needed, was accomplished by endoscopic argon plasma coagulation. Based on the follow-up data, the rebleeding rate was compared between patients who had/had not undergone endoscopic treatment. Multivariate analysis was performed using Cox proportional hazard regression model to identify the predictors of rebleeding. We defined the OGIB as controlled if there was no further overt bleeding within 6 months and the hemoglobin level had not fallen below 10 g/dl by the time of the final examination. RESULTS: The overall rebleeding rate over a median follow-up duration of 30.5 months (interquartile range 16.5-47.0) was 33.8% (23/68 cases). The cumulative risk of rebleeding tended to be lower in the patients who had undergone endoscopic treatment than in those who had not undergone endoscopic treatment, however, the difference did not reach statistical significance (P = 0.14). In the majority of patients with rebleeding (18/23, 78.3%), the bleeding was controlled by the end of the follow-up period. Multiple regression analysis identified presence of multiple lesions (≥3) (OR 3.82; 95% CI 1.30-11.3, P = 0.02) as the only significant independent predictor of rebleeding. CONCLUSION: In most cases, bleeding can be controlled by repeated endoscopic treatment. Careful follow-up is needed for patients with multiple lesions, presence of which is considered as a significant risk factor for rebleeding.

Correlation between gastric transit time measured by video capsule endoscopy and gastric emptying determined by the continuous real-time 13C breath test (BreathID system).

BACKGROUND/AIMS: The aim of this study was to determine the possible existence of a correlation between the gastric transit time (GTT) measured by video capsule endoscopy (VCE) and the parameters of gastric emptying determined using 13C breath test (BreathID system). METHODS: Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects were randomly assigned to undergo VCE using the PillCam SB capsule endoscopy system or the 13C breath test for 4 hours after a test meal (400 kcal per 400 mL) containing 100 mg of 13C acetic acid administered after overnight fasting. The VCE images were analyzed and the GTT was determined using the proprietary RAPID software. The parameters, namely T lag, T 1/2 and GEC were calculated using the Oridion Research Software (ß version). The GTT measured by VCE and the parameters of gastric emptying were compared statistically. RESULTS: No significant correlation was observed between the GTT and T lag (p = 0.5263), T 1/2 (p = 0.4100) or GEC (p = 0.2410), as determined by calculation of the Spearman's rank correlation coefficient. CONCLUSIONS: GTT measured by VCE cannot serve as asubstitute for the gastric emptying time measured bythe 13C breath test.

Diagnostic Ability of Ultrasonography Compared with Computed Tomography for Assessing Rectal Feces.

Objectives: Chronic constipation is a common gastrointestinal disorder, and management is crucial. Computed tomography (CT) is useful for evaluating rectal fecal mass but limited owing to radiation exposure, cost, and inaccessibility at certain facilities. Ultrasonography (US) avoids these pitfalls, but it is unknown whether it accurately assesses rectal feces. In this study, we evaluated the diagnostic performance of US compared with CT as the gold standard for assessing rectal feces. Methods: We prospectively evaluated rectal fecal mass retention using US performed within 1 h of CT to assess the degree of agreement between methodologies. Rectal stool findings were evaluated on three levels: no stool (R1), presence of stool (R2), and hard stool filling (R3). Results: The sample included 100 patients (55 men, 45 women), of whom 47 were constipated. The kappa coefficients for rectal content detection were excellent between US and CT (p <0.001). Eighty-two cases (R1: 46 cases; R2: 28 cases; R3: 8 cases) were matched with CT and US findings, and 18 were not. Cases that did not match had low urine or high gas volumes. CT and US findings showed high agreement in constipation (kappa coefficient 0.674, p <0.001) and non-constipation groups (kappa coefficient 0.677, p <0.001). All cases with R3 on CT were found in the constipation group, while more than half of the cases with R1 on CT were in the non-constipation group. Conclusions: CT and US showed high agreement in evaluating rectal fecal mass retention, indicating that US can substitute CT.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). METHODS: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 µg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. KEY RESULTS: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. CONCLUSION & INFERENCES: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

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.