Diagnosis and treatments for oropharyngeal dysphagia: effects of capsaicin evaluated by newly developed ultrasonographic method.

Oropharyngeal dysphagia (OD) is a common symptom in the older people, and may cause fatal complications such as aspiration pneumonia. However, there is no established treatment for OD. The relationship between the transient receptor potential vanilloid 1 (TRPV1) and substance P released by activated TRPV1 was recently demonstrated. Further, there are several reports showing that capsaicin, a specific agonist of TRPV1, can improve OD. Currently, the evaluation of swallowing is mainly performed by videofluoroscopic examination. However, there are no reports on the clinical application of ultrasonography using tissue Doppler imaging. In this review, we describe the pathophysiology and treatments for OD, introduce our novel US method to evaluate cervical esophageal motility, and then outline our clinical study examining the effects of capsaicin, a specific TRPV1 agonist, in older patients with OD.

Usefulness of ultrasonographic evaluation of stool and/or gas distribution for the treatment strategy of chronic constipation.

BACKGROUND AND AIM: This study aimed to evaluate the capability of ultrasonography to predict favorable outcomes of various medical therapies in patients with chronic constipation. METHODS: We enrolled 223 patients with chronic constipation (75 men, 148 women; mean age 62.9 ± 3.4 years). Transverse diameters of four segments of the colon (ascending [A], transverse [T], descending [D], sigmoid [S]), and the rectum [R]) were measured. The patients' stool and/or gas distribution was evaluated using the constipation index (CI) ([A + T + D + S + R]/5) and the left/right distribution ratio ([D + S]/[A + T]) according to our previous study. Patients were first treated with fiber- or osmosis-based laxatives for 2 weeks. When constipation was not alleviated, stimulant-based laxatives were added, and the patients were followed for another 2 weeks. RESULTS: Based on their clinical courses, patients were divided into four groups: nonresponders (group A) or responders (group B) to fiber- or osmosis-based laxatives; nonresponders to any medical therapy (group C); and responders to stimulant-based laxatives (group D). The CI was significantly higher in group A than group B (P < 0.05), with the receiver operating characteristic (ROC) curve analysis showing a CI cut-off of 21.2 for predicting favorable outcomes of either fiber- or osmosis-based laxatives (P < 0.05). Left/right distribution ratio was significantly lower in group C than group D (P < 0.05), and the ROC curve analysis showed a left/right cut-off of 0.5 for predicting responders to stimulant-based laxatives (P < 0.05). CONCLUSION: These findings could help physicians predict favorable outcomes with laxatives without side effects for this patient population.

Laparoscopic treatment of median arcuate ligament syndrome in a 16-year-old male.

INTRODUCTION: MALS(Median Arcuate Ligament Syndrome) is rare disease. We experienced the case of MALS and successfully treated by laparoscopic approach. PRESENTATION OF CASE: A 16-year-old male was admitted to our hospital with postprandial epigastric pain that had been present for 3 years. Abdominal three-dimensional computed tomographic angiography showed stenosis of the celiac trunk, and abdominal Doppler ultrasonography showed that the blood flow in the celiac trunk varied between inspiration and expiration. Hence, the patient was diagnosed with median arcuate ligament syndrome. Laparoscopic decompression of the celiac trunk was performed by division of the ligament and partial excision of the celiac plexus. Intraoperative Doppler ultrasonography showed markedly improved flow in the celiac artery. The patient was discharged from hospital on postoperative day 7, and has no recurrent symptoms at 12 months postoperatively. DISCUSSION: This case was most youngest male MALS treated by laparoscopic approach. CONCLUSION: Laparoscopic division of the median arcuate ligament is a minimally invasive, safe, and effective method for decompression of the celiac artery.

New ultrasonographic screening method for oropharyngeal dysphagia: tissue Doppler imaging.

Ultrasound tissue Doppler imaging (US-TDI) has been used to diagnose regional wall motion (WM) abnormalities in coronary artery disease but has not been applied to oropharyngeal diseases. This study aimed first to validate an US-TDI method to assess cervical esophageal (CE) WM and secondly to use the method to evaluate CE WM in patients with oropharyngeal dysphagia (OD). First, we enrolled 22 healthy men (mean age: 59.7 yr) who all underwent both US-TDI and videofluoroscopy (VF) and then esophageal high-resolution manometry (HRM) in the same week. We evaluated the reproducibility of the US-TDI and the relationship between US-TDI and other modalities (VF and HRM). Second, we enrolled 56 mild OD patients (mean age: 58.0 yr) and age- and sex-matched healthy controls. Difference in CE WM between these groups was evaluated by US-TDI. All healthy subjects underwent US-TDI, VF, and HRM successfully, with a sufficiently high reproducibility coefficient for this method, and significant correlation between US-TDI and VF/HRM parameters. US-TDI showed mean time to open CE wall and mean velocity of CE wall opening significantly differed between patients and healthy controls ( P < 0.01). In conclusion, we have developed a US-TDI method for easily assessing CE WM in daily practice and also found significant differences in CE WM between mild OD patients and healthy controls. NEW & NOTEWORTHY A new ultrasonographic screening method using tissue Doppler imaging for oropharyngeal dysphagia was found to be a reliable, reproducible, and well-tolerated method. There is a significant correlation between this new method and conventional methods. This method revealed that patients having mild symptoms of oropharyngeal dysphagia had already significantly delayed cervical esophageal wall opening.

Differences in salivary secretory function between patients with erosive esophagitis and those with nonerosive reflux disease.

BACKGROUND AND AIM: It has been speculated that impaired salivary flow contributes to abnormal acid clearance in patients with erosive esophagitis (EE). For easy and objective assessment of salivary function, we developed a salivary gland blood flow measurement technique using continuous-wave Doppler sonography. In the present study, we evaluated the salivary secretory function in patients with EE and those with nonerosive reflux disease (NERD) using this method. METHODS: Doppler waveform analysis was performed on the facial artery to assess blood inflow to the submandibular gland of 30 healthy subjects (HS). Blood flow was compared before and after secretory stimulation with 1 mL of lemon juice. Saliva was simultaneously collected and weighed before and after stimulation. Continuous-wave Doppler sonography was also performed in patients with EE and NERD. The size of the submandibular gland was compared in 26 patients with EE, 41 patients with NERD, and 86 HS. RESULTS: The submandibular gland blood flow increased after stimulation in all HS. Both within-day and day-to-day reproducibility were good. There was a significant correlation between the percent increase in the maximum velocity and the percent increase in salivary secretion. Although the size of the submandibular gland was not significantly different among the three groups, the percent increase in the maximum velocity in patients with EE was significantly smaller than that in HS. CONCLUSIONS: We have established an easy method of assessing salivary function in daily practice. This study revealed that a decrease in salivary secretory function is involved in the pathology of EE.

Early Intervention with Infliximab Prevents Reoperation in Crohn's Disease: A Single-Center Retrospective Analysis.

BACKGROUND/AIMS: We aimed to evaluate the prognostic factors that can aid in the prevention of first and second surgeries in patients with Crohn's disease (CD). METHODS: The clinical records of 115 patients with CD whose disease onset was between January 1987 and July 2012 were retrospectively investigated. The cumulative rate of bowel resection for CD-related intestinal manifestations following onset until the first surgery and the cumulative rate of reoperation following the first to second surgeries were estimated using the Kaplan-Meier method, and the relationship to each factor was statistically analyzed using the log-rank test. The background factors that influenced the cumulative rate of the first surgery and reoperation were evaluated using univariate and multivariate analyses. RESULTS: The cumulative bowel resection rate was significantly higher in patients with ileocolitis-type CD (p = 0.0018) and in those with CD with smoking habits (p = 0.0315). And the cumulative reoperation rate was significantly higher in patients with ileocolitis-type CD (p = 0.0161) and those without early intervention with infliximab (p = 0.0161). CONCLUSIONS: Ileocolitis-type CD and smoking habit might be initiating factors for bowel resection due to CD-related intestinal manifestations. Early intervention with infliximab likely prevents reoperation for CD recurrence.

Tolerable pain reduces gastric fundal accommodation and gastric motility in healthy subjects: a crossover ultrasonographic study.

BACKGROUND: Obstacles to pain management include patients' reluctance to inform healthcare provides about their pain, and differences in the pain management aims between patients and healthcare providers. The objective of this study was to evaluate whether tolerable pain influences gastric fundal accommodation and gastric motility in healthy subjects. METHODS: We undertook a crossover comparison study to evaluate gastric fundal accommodation and gastric motility in 74 healthy subjects in the presence or absence of tolerable pain. The intensity of tolerable pain was defined as the upper limit of pain compatible with comfortable daily life. Pain was generated by clipping a clothes pin to the ear lobe, and the intensity of pain was adjusted by inserting the gauze between the ear lobe and the pin. Gastric fundal accommodation and gastric motility were assessed by external ultrasonography. The cross-sectional area of the proximal stomach was measured after subjects had taken 100 mL-liquid meals four times, then the amplitude and frequency of antral contractions were measured. RESULTS: The median numerical rating scale of tolerable pain was 3 (interquartile rang 2-4). Gastric fundal accommodation, gastric motility and gastric emptying were all significantly impaired by tolerable pain (P < 0.001 for all comparisons). CONCLUSIONS: Even tolerable pain can reduce gastric fundal accommodation and gastric motility, which could result in anorexia or decreased quality of life. Our findings provide important insights into pain management education for patients tolerating pain and healthcare providers encouraging patients to tolerate pain. This study was registered retrospectively.

Increased enhancement of the liver adjacent to the gallbladder seen with contrast ultrasound: comparison between acute cholecystitis and non-cholecystitis.

BACKGROUND: This study was performed to evaluate the ability of contrast-enhanced ultrasonography (CEUS) with time-intensity curve analysis to demonstrate an increased enhancement of the liver parenchyma adjacent to the inflamed gallbladder, as seen on contrast-enhanced computed tomography. METHODS: The Ethics Committee of our institution approved the study protocol (Kawasaki Medical School, registration number 1277). From April to November 2013, 11 consecutive patients with acute cholecystitis and 16 patients without cholecystitis consented to CEUS (Sonazoid™) and were enrolled in this study. The gallbladder and liver were scanned by one gastroenterologist using harmonic imaging with a low mechanical index. The raw imaging data were stored. Another physician, blinded to all clinical information, constructed the time-intensity curve. The major axis of the region of interest (ROI) was set in segment 5 (pericholecystic area), and the control ROI in segment 8 at the same depth. The intensity ratio (IR) was defined as the peak intensity of segment 5 divided by the simultaneous value of segment 8. The characteristics of the patient with and without acute cholecystitis were compared. The correlation between the IR and the presence of acute cholecystitis was analyzed using binomial logistic regression analysis. A receiver operating characteristic (ROC) curve analysis was performed as well. RESULTS: The IR was significantly higher in the group with than without acute cholecystitis (p = 0.006). The IR correlated significantly with the presence of acute gallbladder inflammation (p = 0.043). The area under the ROC curve was estimated as 0.852 (95% confidence interval, 0.709-0.995). A cut-off value of 2.72 had a sensitivity of 81.8% and a specificity of 81.3%. CONCLUSIONS: The IR obtained by CEUS with time-intensity curve analysis generally demonstrated increased enhancement of the liver parenchyma adjacent to the inflamed gallbladder.

Time Trends in Helicobacter pylori Infection and Atrophic Gastritis Over 40 Years in Japan.

BACKGROUND: Helicobacter pylori infection produces progressive mucosal damage that may eventually result in gastric cancer. We studied the changes that occurred in the presence and severity of atrophic gastritis and the prevalence of H. pylori infection that occurred coincident with improvements in economic and hygienic conditions in Japan since World War II. MATERIALS AND METHODS: The prevalence of H. pylori infection and histologic grades of gastric damage were retrospectively evaluated using gastric biopsy specimens obtained over a 40-year period. Gastric atrophy and intestinal metaplasia were scored using the updated Sydney classification system. RESULTS: The prevalence of H. pylori and severity of atrophy were examined in 1381 patients including 289 patients examined in the 1970s (158 men; mean age, 44.9 years), 787 in the 1990s (430 men; 44.2 years), and 305 in the 2010s (163 men; 53.2 years). Overall, the prevalence of H. pylori infection decreased significantly from 74.7% (1970s) to 53% (1990s) and 35.1% (2010s) (p < .01). The prevalence of atrophy in the antrum and corpus was significantly lower in the 2010s (33, 19%, respectively) compared to those evaluated in either the 1970s (98, 82%) (p < .001) or 1990s (80, 67%) (p < .001). The severity of atrophy and intestinal metaplasia also declined remarkably among those with H. pylori infection. CONCLUSIONS: There has been a progressive and rapid decline in the prevalence of H. pylori infection as well a fall in the rate of progression of gastric atrophy among H. pylori-infected Japanese coincident with the westernization and improvements in economic and hygienic conditions in Japan since World War II.

Clinical characteristics of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito.

BACKGROUND: The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed 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 randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. RESULTS: There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. 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 treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week 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 and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. CONCLUSIONS: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals). TRIAL REGISTRATION: (UMIN000005880).

A randomized, placebo-controlled, double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: the G-PRIDE study.

BACKGROUND: 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). METHODS: 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). RESULTS: 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 < 0.05). The 8-week treatment with RKT was more effective for improvement of the degree of MCS score in patients with a low body mass index (<22) (P < 0.05) and significantly improved the acid-related dysmotility symptoms of FSSG in female and elderly patients (≥ 65 years). CONCLUSION: There were no significant differences in improvement of GERD symptoms in patients with PPI-refractory NERD between these groups. However, RKT may be useful for improving mental QOL in non-obese patients and acid-related dyspeptic symptoms, especially in women and the elderly.

Pathophysiology and treatment of patients with globus sensation--from the viewpoint of esophageal motility dysfunction.

"Globus sensation" is often described as the sensation of a lump in the throat associated with dry swallowing or the need for dry swallowing, which disappears completely during eating or drinking and for which no organic cause can be established. Due to the uncertain etiology of "globus sensation", it remains difficult to establish standard treatment strategies for affected patients. Lately most attention has been focused on gastroesophageal reflux disease and several reports have indicated that there is a close relationship between esophageal acid reflux and globus sensation. Nowadays, empirical therapy with a high dose of a proton pump inhibitor (PPI) is considered to be indicated for patients with globus sensation, after excluding organic diseases such as pharyngeal cancer, Zenker's diverticulum, or thyroid enlargement. If patients are nonresponsive to PPI therapy, evaluation of esophageal motility should be done. In our recent study, 47.9% had abnormal esophageal motility, with the most common esophageal motility abnormality being an ineffective esophageal motility in PPI-resistant patients with globus sensation. This suggests that prokinetics alone or adding prokinetics to PPI should be the treatment to be considered, although few studies have investigated the efficacy of prokinetics in the treatment of patients with globus sensation. If patients without any esophageal motility dysfunctions are nonresponsive to PPI therapy, either cognitive-behavioral therapy, anti-depressants, or gabapentin could be helpful, although further well-designed, randomized controlled large-scale studies will be necessary to determine the effectiveness of each treatment strategy on patients with globus sensation.

Intragastric infusion of rikkunshito (kampo) induces proximal stomach relaxation in conscious dogs.

PURPOSE: Abnormal proximal gastric relaxation is one of the causes of functional dyspepsia. The purpose of this study is to use a barostat in conscious dogs to determine the effects of rikkunshito, which is considered to have beneficial effects on functional dyspepsia, on the proximal stomach. METHODS: Eight beagles were used. A gastrocutaneous fistula and force transducers were surgically implanted in the middle corpus and gastric antrum and duodenum, respectively. After a recovery period, a plastic bag was inserted through the gastrocutaneous fistula and the proximal stomach was distended using a barostat. First, four dogs were used to investigate the pressure-volume relation in the fasted and postprandial phases. Second, the stomachs of four different dogs were continuously distended at minimal distending pressure +2 mmHg, and 5 min later were infused with warmed liquid rikkunshito (2 g/20 mL) or water through the gastrocutaneous fistula. Finally, changes in the proximal gastric volume and gastrointestinal motility were observed. RESULTS: The proximal stomach was significantly more pliable in the postprandial phase than in the fasted phase. The proximal gastric volume increased immediately after liquid infusion under constant pressure in both phases and duodenal motility was accelerated. The effect of rikkunshito was significantly greater and lasted longer than that of water. No significant difference between the effects during the fasted or postprandial phase and no change in the gastric antrum motility were observed when rikkunshito was infused. CONCLUSION: These results indicate that rikkunshito accelerates duodenal motility and relaxes the proximal stomach.

S100A expression and interleukin-10 polymorphisms are associated with ulcerative colitis and diarrhea predominant irritable bowel syndrome.

BACKGROUND: Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling. AIMS: The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls. METHODS: mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale. RESULTS: Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls. CONCLUSION: Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.

A Study on the Efficacy of Proton Pump Inhibitors in Helicobacter pylori-Negative Primary Care Patients with Dyspepsia in Japan.

BACKGROUND/AIMS: There have been few studies on the efficacy of proton pump inhibitors and the doses required to treat dyspeptic symptoms observed in clinical practice. The aim of this study was to compare the efficacy of different doses of omeprazole and different administration methods in Helicobacter pylori-negative, dyspeptic patients. METHODS: Patients with chronic upper abdominal symptoms within the previous 3 months were randomly divided into three groups: a daily, omeprazole 20 mg treatment group (OPZ20, n=61); a daily, omeprazole 10 mg treatment group (OPZ10, n=72); and an on-demand omeprazole 20 mg treatment group (on-demand, n=62). After 4 weeks of administration of the drug, symptom improvement rates were evaluated based on the Overall Global Severity score. RESULTS: The rates of symptom improvement after 4 weeks of treatment were 65.6% (40/61) in the OPZ20 group, 47.2% (34/72) in the OPZ10 group, and 50.0% (31/62) in the on-demand group. The OPZ20 group exhibited a significantly higher improvement rate (p=0.034) than the OPZ10 group. The OPZ20 group had significant improvements in regurgitation, postprandial fullness, vomiting, and bloating compared with the OPZ10 group. CONCLUSIONS: Daily treatment with 20 mg of omeprazole was efficient in treating upper abdominal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, number UMIN000002621.

Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study): A multicentre, prospective, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Since the publication of the Rome III criteria for functional dyspepsia (FD), the evidence about the efficacy of half-dose of proton pump inhibitors for dyspepsia symptoms have been limited. OBJECTIVE: To examine the efficacy of lansoprazole for functional dyspepsia (FD) diagnosed with the Rome III criteria by the multicentre, double-blind, randomized, placebo-controlled study in Japan. METHODS: A total of 54 FD participants were randomized to lansoprazole 15 mg once daily or placebo for a 4-week double-blind treatment period. The primary efficacy endpoint was an overall dyspeptic symptom relief rate evaluated by 5-point Likert scale scores. The alteration of dyspeptic symptom scores during the study period was also assessed. RESULTS: At week 4, the overall dyspeptic symptom relief rates were higher in the lansoprazole group (30.4%) than in the placebo group (6.7%) (p = 0.045). The scores for epigastric pain (p = 0.045) and epigastric burning (p = 0.03) were significantly improved in the lansoprazole group compared to the placebo group, whereas the improvement of the scores for postprandial fullness (p = 0.81) and early satiation (p = 0.33) was not different between lansoprazole and placebo groups. CONCLUSIONS: Lansoprazole 15 mg ameliorates dyspeptic symptoms, particularly the epigastric pain syndrome-related symptoms of FD.

Esophageal motor dysfunction plays a key role in GERD with globus sensation--analysis of factors promoting resistance to PPI therapy.

OBJECTIVE: Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. DESIGN: The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. RESULTS: A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. CONCLUSION: Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.