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Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis.One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups.The median salivary pepsin concentration in patients with AET 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test ( 109 ng/mL) to diagnose patients with AET 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group.In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.

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.

Background: Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. Objective: To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Methods: Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. Results: In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions (P < 0.05), the complete bolus transit (P < 0.01), and the residual pressure of lower esophageal sphincter (P < 0.05) in these patients. The overall score (P < 0.01) and the subscale scores of acid reflux syndrome (P < 0.05), abdominal pain (P < 0.05), and indigestion syndrome (P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. Conclusions: In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

Background Elobixibat has been approved as a new therapeutic drug for chronic constipation. Only the pharmacological efficacy and safety profile of pre-breakfast administration of elobixibat had been previously demonstrated. Objective We evaluated the efficacy and safety profile of pre-dinner administration of elobixibat in patients with functional constipation in a retrospective observational study. Methods Patients aged 20 years or older diagnosed with functional constipation by the Rome IV criteria from June 1, 2018, to January 17, 2019. The evaluation time points were at the start and 1, 2, 4, and 8 weeks after treatment. The primary end point was frequency of spontaneous bowel movements per week. The secondary end points were changes in Bristol Stool Form Scale score, onset time required for spontaneous defecation after administration, percent of patients with spontaneous defecation within 24 hours and 48 hours after the first administration, improvement of abdominal pain or abdominal bloating evaluated by a visual analog scale, and total score and each subscore of the Japanese-Translated Version of Patient Assessment of Constipation Quality of Life Questionnaire. Results Pre-dinner administration of elobixibat was associated with significantly increased frequency of spontaneous bowel movements and improved Bristol Stool Form Scale score at 1, 2, 4, and 8 weeks after treatment. The mean onset time until spontaneous defecation after treatment was 4 to 5 hours, which was earlier than that by conventional constipation treatment drugs and almost constant within an individual during the treatment period. Spontaneous defecation was achieved by 85.4% within 24 hours and 90.2% within 48 hours after the first administration. Elobixibat also improved patients’ quality of life, which was evaluated by the Japanese-Translated Version of Patient Assessment of Constipation Quality of Life Questionnaire without adverse events. Conclusions Pre-dinner administration of elobixibat improved constipation, abdominal pain and bloating, and patient quality of life by management of fixed defecation. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

The role of the esophagus is to transport food to the stomach rapidly and safely. The transportation of food is controlled by the complex esophageal motility of the upper and lower esophageal sphincters which operate in a precise manner to produce peristaltic contraction. Patients with functional esophageal diseases such as gastroesophageal reflux disease (GERD), esophageal achalasia, and ineffective esophageal motility (IEM) often suffer from various symptoms of dyspepsia, including dysphagia, chest pain, heartburn, epigastralgia, bloating, nausea, foreign-body sensation, and discomfort.

BACKGROUND Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P

The aim of this study was to investigate the efficacy of rikkunshito (RKT), a traditional Japanese medicine, combined with proton pump inhibitor (PPI) in patients with PPI-refractory non-erosive reflux disease (NERD). Patients with PPI-refractory NERD (n = 242) were randomly assigned to the RKT group [rabeprazole (10 mg/day) + RKT (7.5 g/t.i.d.) for 8 weeks] or the placebo group (rabeprazole + placebo). After the 4- and 8-week treatments, we assessed symptoms and quality of life (QOL) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG), Gastrointestinal Symptom Rating Scale (GSRS), and Short-Form Health Survey-8 (SF-8). There were no significant differences in FSSG and GSRS score improvement between these groups after the 4- and 8-week treatments. The mental component summary (MCS) scores of the SF-8 improved more in the RKT group (from 45.8 ± 8.1 to 48.5 ± 7.4) than in the placebo group (from 47.7 ± 7.1 to 48.4 ± 7.5) after the 4-week treatment (P

Facemask Ventilation during Induction of Anesthesia: How “Gentle” Is “Gentle” Enough? Shiroh Isono;Matthias Eikermann;Takeo Odaka; Anesthesiology

Summary Background There have been few reports that compare the effect of histamine H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) using continuous gastric pH monitoring for a long duration. Aim To assess the early effects of both drugs on gastric pH using a wireless pH monitoring system. Methods The test was conducted by a cross-over test: 10 healthy male volunteers were administered famotidine 20 mg twice a day and lansoprazole 30 mg once a day. Monitoring of gastric pH over four consecutive days was performed using a unique method we have developed that is an elaboration of the Bravo system. Results The time to reach a pH level of 3 or more with famotidine was significantly shorter than that for lansoprazole. The pH3 holding time ratio of famotidine during the first 4 h of administration was significantly higher than that of lansoprazole. The pH3 holding time ratio on each day from day 1 to day 3 was significantly higher following lansoprazole administration compared with famotidine administration. Conclusions Famotidine was shown to act quickly in elevating gastric pH; however, lansoprazole was superior to famotidine in terms of its ability to elevate gastric pH for a long duration.

Background The Bravo system was designed mainly to monitor esophageal pH, and there have been no reports on gastric pH monitoring using this system. Objective To place the Bravo capsule on the gastric wall and monitor gastric pH. Design Experimental clinical trial with the cooperation of volunteers. Setting Academic medical center. Patients Eleven volunteers (9 men, 2 women; mean age 38 years; 3 had symptoms of GERD). Interventions The Bravo system was introduced into the esophagus and stomach along a thin endoscope and capsules were attached, one each to the esophageal and gastric walls under direct vision through the endoscope. Esophageal and gastric pHs were simultaneously monitored. Results The 2 capsules were successfully placed in 10 of the 11 subjects, and both esophageal and gastric pHs were monitored for 48 hours in 9 subjects. Mild to moderate precordial pain was observed in 7 subjects, but no other complications or side effects were observed in this study. The gastric pH of 10 subjects increased after meals and returned to baseline pH 2 hours later. Decrease of esophageal pH was observed 1 hour after a meal in the symptomatic subjects and corresponded to the time when gastric pH decreased secondary to the increase of pH with meals. Conclusions The Bravo capsule is easily placed on the gastric wall under endoscopic assistance and enables long ambulatory monitoring of gastric pH.

Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrate's effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre- and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Student's t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P0.01) and the total colon (P0.05). During rectal filling, mosapride lessened the first sensation (P0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.

OBJECTIVE: We aimed to clarify the time course of the Helicobacter pylori stool antigen (HpSA) level during and after eradication therapy and to determine the appropriate time of measurement of HpSA to evaluate eradication. METHODS: The subjects were 47 patients who were positive for H. pylori. The patients underwent a 1-wk regimen of triple therapy. The outcome of the eradication therapy was judged by urea breath test, culture, and histology 6 wk after the end of treatment. The HpSA level was serially measured nine times from before therapy until 12 wk after the end of therapy. RESULTS: In the group with successful eradication, HpSA became negative immediately after the end of therapy and the negativity persisted. In contrast, in the noneradication group HpSA became negative immediately after therapy, but became positive again within 2 wk after the end of therapy. The mean absorbance value of the HpSA test on the 4th day after the initiation of eradication therapy was significantly higher in the noneradication group than in the group with successful eradication. The diagnostic accuracy of the HpSA test increased to ≧90% 2 wk after therapy and thereafter. Comparison of the diagnostic accuracy at 4 wk after the end of therapy showed no significant differences with that at 2, 6, 8, and 12 wk after the end of therapy. CONCLUSIONS: The course of the HpSA levels during and after eradication therapy in patients with successful eradication was quite different from that in noneradication patients. Measurement of HpSA was useful to evaluate eradication, and the appropriate evaluation of the outcome of treatment could be made as early as 2 wk after the end of therapy.

There have been many studies about the diagnosis of gastric emptying using 13C octanoic acid breath test (13C-OABT) since 1993 when Ghoos el al.(1993) first reported, and various index of 13C-OABT was investigated for the correct diagnosis. Especially, the half empting time (T1/2) calculated from fitting curve and the maximum peak time (Tmax) obtained by the actual 13C-excreation curve are used most frequently. However, some discrepancy between T1/2 and Tmax in the same subject is observed. In this report, we compared T1/2 with Tmax and discussed usefulness and problems of 13C-OABT. Subjects were 20 healthy volunteers and 55 patients with suspect of delayed gastric empting ; 50 with Diabetes Mellitus and 5 with functional dyspepsia. The subjects consumed a standard 280 kcal test meal consisting of 100 mg of 13C-octanoic acid. Breath samples were obtained before and every 15 min. after the consuming of test meal for a total of 6h. Correlation between T1/2 and Tmax was examined. As results, a significant correlation between T1/2 and Tmax was observed (γ=0.84). However, the diagnosis of T1/2 did not agree with that of Tmax in 29.7% ; 15 of 37 patients diagnosed as delayed gastric emptying by T1/2 were judged normal by Tmax. The 13C-excreation curve of these 15 patients showed delayed recovery in late phase. We speculated this delayed recovery did not result in true delayed gastric emptying but was the consequence of metabolic effect probably due to liver function. If so, the diagnosis using Tmax is considered more accurate than that using T1/2 in 13C-OABT, however requiring further study to confirm this speculation.

Ideally, the diagnosis of irritable bowel syndrome (IBS) would be achieved using a minimal number of procedures. It is presumed that bowel gas is related to IBS, and it is easily visualized by plain abdominal radiograph. In the present study, to clarify the relationship between IBS and the quantity of bowel gas, the measured bowel gas volume using plain abdominal radiographs was compared with the pathology of IBS.Plain abdominal radiographs were digitized and transmitted to a computer (computed radiography) in 30 IBS patients and 30 normal controls. The quantity of bowel gas, determined as the pixel value on images and standardized by physique, was defined as the gas volume score (GVS). Using the mean +/- 2SD of GVS in the control group as the normal score, IBS patients were divided into three groups: high, normal, and low. To examine the sequential reproducibility of a similar quantity of bowel gas, a second plain abdominal radiography was performed about 2 months later, and the GVS were compared. The colonic transit time was determined using radiopaque markers.There was a strong correlation between the quantities of bowel gas measured by two independent gastroenterologists. The mean GVS of IBS patients was significantly higher than that in the control group (p0.001). The sequential reproducibility was recognized in all 10 IBS patients. There was no significance between colonic transit time and GVS, nor between symptoms and GVS.Abdominal gas was analyzed objectively by using GVS, and GVS was considered to represent a useful tool for the diagnosis of IBS.

Sennosides, the most popular irritant laxatives, cause purgative actions in the intestine through biotransformation to rhein anthrone; however, the underlying mechanisms remain unclear. The purpose of this study was to define colonic motor actions of sennoside A with special reference to purgative action. Mice received a single oral dose of 30 mg/kg sennoside A, and the colon was removed about 6 hr later. Contractions of longitudinal and circular muscles were recorded using an isometric force transducer and a pressure transducer, respectively. In longitudinal muscle preparations, spontaneous contractions were augmented in distal colon compared to control. In circular muscle preparations, contractions were reduced in the proximal colon, but increased in the distal colon. Particularly in the proximal colon, the frequency of high-amplitude contraction was reduced. In the control group, non-adrenergic, non-cholinergic treatment decreased the amplitude of contractions in the proximal colon, but not in the distal colon. In the sennoside A group, non-adrenergic, non-cholinergic treatment only slightly depressed the amplitude of contractions in the proximal and distal colon. To confirm a causal relationship between luminal prostaglandin level and purgative action of sennoside A, the mice were treated with indomethacin. Significant changes induced by sennoside A were attenuated by indomethacin treatment. The present study indicates that spontaneous motility is inhibited by sennoside A in the proximal colon, but accelerated in the distal colon, and that effects are associated with luminal prostanoid level and only partially with cholinergic nerve mediation.

Irritable bowel syndrome is a functional gastrointestinal disorder characterized by abnormal sensation and motility in the lower gastrointestinal tract. In constipation-type irritable bowel syndrome, decreased bowel motility causes stagnation of feces and gas, resulting in enhanced pain sensation of the bowel. Mosapride citrate is a selective serotonin 5- HT4 receptor agonist and enhances propulsive activity throughout the gastrointestinal tract. Mosapride citrate was orally administered to 11 patients with constipation-type irritable bowel syndrome to investigate its effect on this disease. The result showed that mosapride citrate alleviated abdominal pain and abdominal distension, loosened stools, shortened bowel transit time, and decreased flatus in the bowel. The results suggest that mosapride citrate is useful for the treatment of irritable bowel syndrome.

Background and Aims: To evaluate gastrointestinal motility by abdominal auscultation. Methods: Abdominal auscultated sounds of 20 healthy adults and 10 diabetes mellitus patients with delayed gastric emptying were digitally recorded and then analyzed by computer while simultaneously monitoring the motility of the antrum of the stomach by ultrasonography. The auscultated sound, when the stomach wall was moving, was regarded as the gastroduodenal (GD) sound and when not moving as the intestinal (I) sound. The sound index (SI; the sum of the amplitude) was calculated to indicate the power of sound. Sounds were recorded for 15 min under fasting conditions and 60 min after a liquid meal. In six healthy adults, the gastroduodenal pressure was recorded under abdominal auscultation to detect any correlation between the motility index (MI; the sum of the area under the curve) and SI. Results: A definite increase in the SI of the GD sound was observed after the liquid meal in comparison with that of the I sound. A positive correlation (r = 0.678) was observed between the SI of the GD sound and MI, thus, it was considered that the GD sound reflected the motility of the gastroduodenal wall. In the diabetes mellitus patients, the SI of the GD sound was significantly lower after food intake than in healthy adults. Conclusion: The results of the present study indicate that the abdominal auscultation test could be used as a new diagnostic method to detect any abnormality in gastrointestinal motility.

Calcium polycarbophil shortened total colonic transit time (P < 0.05), increased bowel frequency and improved defecation difficulty in four patients with non-traumatic spinal cord disorders. Polycarbophil may be useful for the treatment of constipation.

Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD).To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD.Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two).In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p0.05) and total colon (p0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p0.01) and straining (p0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p0.05), evidence of paradoxical sphincter contraction on defecation (PSD).Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.

Background/Aim: One of the features of gastroesophageal reflux disease (GERD) in Japan is that its frequency and severity tend to increase in elderly women. In addition, elderly patients (≥65 years) with non-erosive reflux disease (NERD) present with typical symptoms more frequently than do non-elderly patients with NERD. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and enhances gastric emptying and improves gastric accommodation. Our previous prospective randomized multicenter placebo-controlled study, the G-GRIDE study, showed that RKT combined with a standard-dose of rabeprazole (RPZ) therapy significantly improved the acid-related dysmotility (ARD) symptoms in elderly patients with PPI-refractory NERD. The aim of this study was to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. Methods: Two hundred forty-two patients with PPI-refractory NERD were enrolled from August 2011 to July 2012 at 71 hospitals in Japan. Patients were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) plus rikkunshito (7.5 g/t.i.d.) (RKT group) or RPZ plus placebo (PL group) therapy. Of the 242 patients, 95 were elderly patients (≥65 years) with ARD (RKT group: n=52, PL group: n=43). We analyzed the changes using the 12 subscale score of the frequency scale for the symptoms of GERD (FSSG) at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. Results: No significant differences were seen between the 2 groups in terms of subject background. The FSSG score (mean±SD; at 0, 4, and 8 weeks) in both the RKT [16.0±7.0; 9.9±8.4; 7.0±6.4] and PL [15.1±6.4; 10.9±6.7, 11.1±8.5] groups significantly decreased after the treatment. However, the degree of improvement of total and ARD scores of FSSG after 8 weeks of treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach after meals, and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. Conclusion: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. RKT was especially effective for resolving postprandial GERD symptoms (heavy feeling in stomach after meals, sick feeling after meals, and heartburn after meals).

Computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) is a new dyeless imaging technique that enhances mucosal and vascular patterns. However, a method for selecting a suitable wavelength for a particular condition has not been established. The aim of this study is to evaluate the color difference method for quality assessment of FICE images of the intrapapillary capillary loop in magnifying endoscopy for esophageal squamous cell carcinoma. The color difference between 60 microvessels and background mucosa observed using the magnifying endoscope was 8.31±2.84 SD under white light and 12.26±3.14 (p=0.0031), 11.70±4.49 (p=0.0106), and 17.49±5.40 (p

Background: More than 50% of non-erosive gastroesophageal reflux disease (NERD) patients have a poor response to proton pump inhibitors (PPIs) treatment. Recently, it was reported that esophageal motility disorder involving a decline in esophageal clearance contributes to refractory for PPIs. However, there was few reports focused to esophageal motility of patients with NERD refractory for PPIs and there is no established strategy for treatment of refractory NERD. Aims: To clarify the characteristic of patients with refractory NERD, we investigated the esophageal function using MII-EM. In addition, we also evaluated the efficacy of rikkunshito which is a gastrointestinal prokinetic agent. Methods: In this study, 24 NERD patients including 15 patients with NERD refractory for PPIs treatment. Refractory NERD was defined as a score of more than 6 points in the QUEST questionnaire after PPI treatment for over than 4 weeks. After wash-out of gastrointestinal-related drugs, all enrolled patients underwent the examinations using MII-EM and then started oral administration of rikkunshito (7.5 g/ day). After rikkunshito treatment for 8 weeks, the examinations using MII-EM was performed again. Also, symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before and 4 weeks / 8 weeks after starting the rikkunshito treatment. Results: At first examination using MII-EM, 71.4% of the refractory NERD patients had peristaltic contraction rate (PC rate) deviating from the standard value (≧80%) and 85.7% of them had a complete bolus transit rate (CBT rate) deviating from the standard value (≧75%). On the other hand, in the 9 patients other than the refractory NERD, the rate of patients with such deviation was 25.0% and 50.0%, respectively. The rate of patients with a resting LES pressure deviating from the standard value was comparable between the two patient groups. Next, we also evaluated the efficacy of rikkunshito in the refractory NERD. Rikkunshito significantly improved the LES residual pressure during swallow from 7.2 ± 5.1 mmHg to 5.2 ± 4.1 mmHg, PC rate from 52.4 ± 34.6% to 75.5 ± 31.1% and CBT rate from 51.5 ± 27.4% to 81.8 ± 16.0%. In assesment of symptoms with GSRS, rikkunshito significantly improved score of acid reflux symptoms, dyspepsia-like symptoms and total gastrointestinal symptoms. Conclusion: These results suggested that the refractory NERD patients had a disorder of esophageal motility and that rikkunshito ameliorated the gastrointestinal symptoms through improvement of the esophageal and LES motility disorder. We propose the application of rikkunshito as a strategy to treat patients with NERD refractory for PPIs.

Background: Proton pump inhibitors (PPI) are the drug of first choice for treating patients with gastroesophageal reflux disease (GERD). However, about 50% of non-erosive reflux disease (NERD) patients have a poor response to PPI treatment. It is reported that esophageal motility disorder involving a decline in esophageal clearance contributes to the poor PPI response. Accordingly, a drug capable of enhancing esophageal motility would be beneficial in the treatment of NERD patients. Rikkunshito, a gastrointestinal prokinetic agent, is known to improve esophageal clearance in GERD patients and gastric emptying in functional dyspepsia patients and to increase secretion of ghrelin in rats. Aim: To clarify the efficacy of rikkunshito in NERD patients, we evaluated the effects of rikkunshito on esophageal and lower esophageal sphincter (LES) motility and symptoms. Methods: Fifteen patients were enrolled in the study. They were diagnosed as having NERD according to endoscopic testing and the score (6 points or more) obtained on the questionnaire for the diagnosis of reflux disease (QUEST). All patients stopped taking all gastrointestinal-related drugs for over 1 week prior to rikkunshito treatment, and were administered rikkunshito (7.5 g per day, orally) for 8 weeks. Esophageal and LES functions during liquid or semisolid swallow were evaluated using MII-EM following gold standard methods before and after rikkunshitotreatment. Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before, 4 weeks after, and 8 weeks after treatment. Results: Rikkunshito-treatment significantly improved the mean of complete bolus transit (CBT) during liquid or semisolid swallow from 60.7±7.7% to 90.0±5.8% (p 79%, semisolid: >69%) for CBT decreased from 53.3% to 16.7% and from 60.0% to 33.3% after treatment, respectively. In manometry evaluation, rikkunshito significantly improved the mean of LES residual pressure during liquid swallow from 6.0±1.3 mmHg to 3.8±1.4 mmHg (p

Chronic intestinal pseudo-obstruction (CIP) is a rare and highly morbid syndrome characterised by impaired gastrointestinal propulsion together with symptoms and signs of bowel obstruction in the absence of any lesions occluding the gut lumen (tumours, adhesive peritonitis, and so on).1 CIP is thought to have two forms: myogenic and neurogenic.1 Comorbid urinary retention may also occur.2 Postural hypotension is not a feature in CIP. However, we recently had such a CIP patient with profound postural hypotension, which was detected only by a head up tilt test, and he was finally diagnosed as pure autonomic failure (PAF). A 59 year old man gradually (over two months) developed intractable nausea and vomiting immediately after taking meals, although he did not have dysphagia. He also had abdominal distension, discomfort, and mild difficulty in defaecation. At that time, he had no features to suggest autonomic failure affecting other systems than the gut, such as postural dizziness or genitourinary dysfunction. Six months later, he was admitted to a gastrointestinal surgery hospital because of these symptoms, at which time he was emaciated. However, gastric and colonic endoscopy showed no organic lesions. As abdominal x ray findings continued to support the suspicion …

To objectively evaluate the effect of TJ-68 on colonic spasms during colonoscopy.One hundred and one patients subjected to screening colonoscopy were randomly assigned to two groups: TJ-68 in 51 subjects and saline as the control in 50. The endoscope was inserted into the sigmoid colon, then a spastic region was identified and the tip of the colonoscope was positioned at a distance of about 10 mm from the spastic region. The endoscopic view was recorded before and after direct spraying of the TJ-68 solution or warm saline. The intraluminal area of the spastic region was serially measured using a computer image analyzer and expressed as pixel counts. The area under the curve (AUC) was calculated from the pixel curve. Statistical significance was assessed by Wilcoxon's test and Mann-Whitney U test.The mean AUC of the spastic region before and after TJ-68 spraying was 29,128 and 121,943 pixels, respectively, while with saline, it was 31,635 pixels and 48,617 pixels, respectively. Thus, the AUC significantly increased after TJ-68 spraying compared with the spraying of saline (P0.001).Direct spraying of TJ-68 on the colonic mucosa suppressed colonic spasm and it may be useful during colonoscopy when anticholinergic agents are contraindicated.