Feasibility and safety of endoscopic submucosal dissection for lesions in proximity to a colonic diverticulum.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for diverticulum-associated colorectal lesions is generally contraindicated because of the high risk of perforation. Several studies on patients with such lesions treated with ESD have been reported recently. However, the feasibility and safety of ESD for lesions in proximity to a colonic diverticulum (D-ESD) have not been fully clarified. The aim of this study was to evaluate the feasibility and safety of D-ESD. METHODS: D-ESD was defined as ESD for lesions within approximately 3 mm of a diverticulum. Twenty-six consecutive patients who underwent D-ESD were included. Two strategic approaches were used depending on whether submucosal dissection of the diverticulum-related part was required (strategy B) or not (strategy A). Treatment outcomes and adverse events associated with each strategy were analyzed. RESULTS: The en bloc resection rate was 96.2%. The rates of R0 and curative resection in strategies A and B were 80.8%, 73.1%, 84.6%, and 70.6%, respectively. Two cases of intraoperative perforation and one case of delayed perforation occurred. The delayed perforation case required emergency surgery, but the other cases were managed conservatively. CONCLUSION: D-ESD may be a feasible treatment option. However, it should be performed in a high-volume center by expert hands because it requires highly skilled endoscopic techniques.

Nocturnal Gastroesophageal Reflux Disease (GERD) and Sleep: An Important Relationship That Is Commonly Overlooked.

Gastroesophageal reflux disease (GERD) is a prevalent, chronic medical condition that affects 13% of the adult population globally at least once a week. Sleep disturbances are frequently encountered in up to 25% of the GERD patients, likely due to nocturnal gastroesophageal reflux (GER). With advance in diagnostic techniques allowing for an improved understanding of involved physiological mechanisms of nocturnal reflux, there is growing evidence of a bidirectional relationship between GERD and sleep disturbances. Furthermore, nocturnal GER is associated with more complicated GERD. Obstructive sleep apnea (OSA) and GERD also have been linked, but to what degree remains controversial. Treatment of nocturnal GER has been shown to improve both subjective and objective sleep measures. The therapeutic approach includes lifestyle modifications and medication individualization and optimization with proton-pump inhibitors serving as the mainstay of treatment. Antireflux surgery and newer endoscopic procedures have been demonstrated to control nocturnal GER.

Durability of Esophageal Motor Disorders Identified on High-Resolution Esophageal Manometry: A Case Series.

BACKGROUND/AIM: Diagnosis of esophageal motor disorders using high-resolution esophageal manometry (HREM) may result in medical, endoscopic or surgical intervention. However, prior to any intervention, durability of the HREM findings should be established. The aim of this case series was to assess 25 patients who had undergone HREM twice, at least 6 months apart, and to determine the durability of the initial manometric diagnosis. METHODS AND PATIENTS: This is a case series of 25 patients who underwent HREM at least twice, 6 months apart, at a large safety net hospital. All patients were evaluated in between the tests for any clinical intervention. Demographics, patients' indication for HREM and clinical presentation were documented as well. RESULTS: Of the 25 patients, HREM results improved in 32%, worsened in 20% and were unchanged in 48%. Some interventions were employed between the first and second HREM diagnosis. Those associated with an improved diagnosis included doubling the proton pump inhibitor (PPI) dose, re-starting a PPI, adding a histamine 2 blocker (H2 blocker) and use of empiric dilation. CONCLUSIONS: In this case series, about half of the patients undergoing two esophageal manometries, at least 6 months apart, demonstrated lack of durability of their initially diagnosed esophageal motor disorder.

Barrett's esophagus patients are becoming younger: analysis of a large United States dataset.

BACKGROUND: Barrett's esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6-8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. METHODS: This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE's variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. RESULTS: The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (- 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30-39: 2.07%, 40-49: 3.64%, 50-59: 6.89%, 60-69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (- 20.8%, p < 0.001), but increased in the other remaining age groups. CONCLUSIONS: The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients' groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30-39 years old.

Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function.

INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

The effect of sleep deficiency on esophageal acid exposure of healthy controls and patients with gastroesophageal reflux disease.

BACKGROUND: Studies have demonstrated a bi-directional relationship between sleep deficiency and gastroesophageal reflux disease (GERD). However, there is limited data on how sleep deficiency affects esophageal acid exposure. We aimed to compare the effect of sleep deficiency on esophageal acid exposure of healthy controls versus GERD patients. METHODS: Eleven patients from each of 2 groups were randomized to undergo pH-testing after 2 consecutive days of 7-8 hours of sleep per night (normal sleep) or 2 consecutive days of 4 hours of sleep per night (deficient sleep). All subjects then crossed over to the other arm, after 1-week washout period. While subjects were instructed to follow the study sleep protocol, actigraphy ensured subjects followed required sleeping time during study period. KEY RESULTS: After normal sleep, all healthy controls had normal esophageal acid exposure. After deficient sleep, 5 healthy controls demonstrated an abnormal pH test. Overall, there was a significant increase in reflux parameters after deficient sleep as compared with normal sleep (% total time-6.15 ± 5.89 vs 1.74 ± 1.54, % upright time-4.72 ± 5.36 vs 0.87 ± 1.28, P < .05, respectively). After normal sleep, 6 GERD patients (54.5%) demonstrated an abnormal pH-testing. After deficient sleep, 10 GERD patients (90.9%) demonstrated an abnormal pH-testing. GERD patients demonstrated significantly higher reflux parameters than healthy controls after normal sleep (% total time-5.02 ± 3.45 vs 1.74 ± 1.54, % upright time-4.11 ± 3.98 vs 0.87 ± 1.28, P < .05, respectively). CONCLUSIONS & INFERENCES: Sleep deficiency increased esophageal acid exposure in both healthy controls and GERD patients. Sleep deficiency also resulted in abnormal pH tests in almost half of healthy controls.

A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation.

BACKGROUND/AIMS: Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. METHODS: We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. RESULTS: One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo ( P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). CONCLUSION: Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center.

Over almost 30 years since functional dyspepsia (FD) was defined, researchers have endeavored to elucidate the pathophysiology of functional gastrointestinal disorders. Now a consensus is emerging that the gastric symptoms of FD are caused mainly by gastric motility abnormalities and gastric hypersensitivity. The involvement of other causative factors including acid, Helicobacter pylori, psychological factors, and diet has been debated, but how they are involved in the manifestation of dyspeptic symptoms remains unclear. We believe that most of those factors cause FD symptoms by inducing gastric motility abnormalities and gastric hypersensitivity via the duodenum. Here, we discuss 2 possible reasons why patients with FD experience chronic upper abdominal symptoms: (1) the possibility that the contents of the duodenum of patients with FD differ from those of healthy persons and the different contents stimulate the duodenum, and (2) the possibility that the duodenum of patients with FD is more sensitive to noxious stimuli because of low-grade inflammation and increased mucosal permeability.

Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders.

BACKGROUND & AIMS: As many as 45% of patients with gastroesophageal reflux disease (GERD) still have symptoms after receiving once-daily proton pump inhibitor (PPI) therapy. We aimed to compare reflux characteristics and patterns between responders and non-responders to once-daily PPI therapy using combined impedance-pH monitoring. METHODS: Patients who reported heartburn and/or regurgitation at least twice per week for 3 months while receiving standard-dose PPI therapy were assigned to the PPI failure group (n = 16). Patients who reported a complete resolution of symptoms on once-daily PPIs for at least 4 weeks were assigned to the PPI success group (n = 13). We collected demographic data and subjects completed the short-form 36 and the GERD health-related quality of life questionnaires. Patients then underwent upper endoscopy and combined esophageal impedance-pH monitoring while on PPI therapy. RESULTS: Four patients in the PPI success group (31%) and 4 patients in the PPI failure group (25%) had abnormal results from the pH test (P = 1.00). Most of the patients in the PPI failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI failure and success group. CONCLUSIONS: We found no difference in reflux characteristics between patients with GERD who had successful vs failed once-daily PPI therapy. Most patients in the PPI failure group (75%) had functional esophageal disorders.

Objective image analysis of non-magnifying image-enhanced endoscopy for diagnosis of small depressed early gastric cancers.

Background Gastric cancers (GC) after H. pylori eradication are difficult to diagnose even by magnifying narrow-band imaging (NBI) or blue laser imaging (BLI) endoscopy. Little is known with regard to non-magnifying (NM)-NBI/BLI for early GC so we examined the efficacy of NM-NBI/BLI for early GC diagnosis. Methods We retrospectively analyzed the images of 29 small (≤ 1 cm) intramucosal GC that had been treated with endoscopic submucosal dissection and 137 benign depressed lesions (BDLs). The brightness and shape of the GCs and BDLs by NM-NBI/BLI were assessed with ImageJ software. Results The NBI/BLI-index, which indicates the brightness of NBI/BLI for visualization, was significantly higher in GC than BDLs in both the H. pylori -infected ( P  = 0.009) and -eradicated group ( P  < 0.0001), indicating that GC exhibited brighter colors than the normal surrounding mucosa. The C-index, which refers to the circularity of the lesion, was also significantly higher in GC than BDLs in both H. pylori -infected ( P  = 0.006) and -eradicated cases ( P  = 0.004). Based on receiver-operating characteristic curve analysis, cutoff values for the NBI/BLI- and C-indices for GC were 1.04 and 0.58 in the H. pylori -infected cases, and 0.98 and 0.64 in the H. pylori -eradicated cases. With the reference value of the NBI/BLI-index set at ≥ 0.69 with the C-index at ≥ 0.21 in the H. pylori -infected and the NBI/BLI-index at ≥ 0.80 with the C-index at ≥ 0.32 in the H. pylori -eradicated cases, both the sensitivity and negative predictive value for early GC were 100 %. A high NBI/BLI-index tended to be associated with a wide length of the intervening part histologically in the H. pylori -eradicated cases ( P  = 0.09). Conclusions The small depressed-type early GC had brighter color and rounder shape compared to BDLs in both H. pylori -infected and -eradicated cases. The NBI/BLI- and C-indices calculated by the image analysis may facilitate identification of small depressed-type GC.

Sex differences in associations among metabolic syndrome, obesity, related biomarkers, and colorectal adenomatous polyp risk in a Japanese population.

To investigate sex differences in the associations among metabolic syndrome, obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a cross-sectional, multicenter study was conducted on 489 consecutive individuals who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of adiponectin and leptin, as well as homeostatic model assessment of insulin resistance were also evaluated. The presence and number of adenomatous polyps, including advanced adenoma, were higher in men than in women. Metabolic syndrome was a risk factor for adenomatous polyps in both sexes. Large waist circumference was an independent risk factor for adenomatous polyps in men, and high BMI and large waist circumference were risk factors for adenomatous polyps in women. Interestingly, low BMI was associated with large adenomatous polyps (≥10 mm) and advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp development only in women. In contrast, the highest quartile of leptin concentration had a 3.67-fold increased adenomatous polyp risk compared with the lowest quartile only in men. These results indicate that regarding colorectal pathogenesis, sex differences were identified in obesity but not in metabolic syndrome. Visceral obesity and a high serum leptin level may be risk factors for colorectal adenomatous polyp development in Japanese men.

The Changing Epidemiology of Gastroesophageal Reflux Disease: Are Patients Getting Younger?

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is a common disease globally with increasing prevalence and consequently greater burden on the Healthcare system. Traditionally, GERD has been considered a disease of middle-aged and older people. Since risk factors for GERD affect a growing number of the adult population, concerns have been raised that increasingly younger people may develop GERD. We aim to determine if the proportion of younger patients has increased among the GERD population. METHODS: The incidence of GERD as well as several variables were evaluated during an 11-year period. Explorys was used to evaluate datasets at a "Universal" and Healthcare system in northern Ohio to determine if trends at a local level reflected those at a universal level. GERD patients were classified into 7 age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, and ≥ 70 years). RESULTS: The proportion of patients with GERD increased in all age groups, except for those who were ≥ 70 years in the universal dataset (P < 0.001) and those who were ≥ 60 years in the Healthcare system (P < 0.001). The greatest rise was seen in 30-39 years in both datasets (P < 0.001). Similarly, the proportion of GERD patients who were using proton pump inhibitors increased in all age groups except for those who were ≥ 70 years in both datasets (P < 0.001), with the greatest increase being the group 30-39 years (P < 0.001). CONCLUSION: Over the last decade, there has been a significant increase in the proportion of younger patients with GERD, especially those within the age range of 30-39 years.

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis.

The risk of gastric cancer (GC) remains in precancerous conditions, including atrophic mucosa and intestinal mucosa (IM), even after H. pylori treatment. To define the molecular changes following H. pylori eradication, molecular alterations in the gastric mucosa with and without GC were evaluated in a long-term follow-up study. A total of 232 biopsy specimens from 78 consecutive patients, including atrophic gastritis patients with follow-up ≥3 y after successful H. pylori eradication (AG group), patients who developed early GC after successful eradication (≥3 y) (GC group), and patients with H. pylori-positive atrophic gastritis (Hp group), were analyzed. H. pylori eradication was associated with significant reductions of methylation of several genes/loci in atrophic mucosa (non-IM), but not in IM. In contrast, the incidence of CpG island methylator phenotype (CIMP) in IM was significantly higher in the GC group than in the AG group. miR-124a-3 methylation and miR-34c methylation were more frequently identified in IM, with very few in non-IM mucosa among the three groups. H. pylori eradication can reverse methylation only in non-IM mucosa. CIMP in IM may have potential as a surrogate maker of GC development, and methylation of miR-124a-3 and miR-34c is a molecular event in IM that may not be associated with GC development.

Esophagography in Patients With Esophageal Achalasia Diagnosed With High-resolution Esophageal Manometry.

BACKGROUND/AIMS: High-resolution esophageal manometry (HREM) is considered to be the gold standard for the diagnosis of achalasia. However, the Japan Esophageal Society recommends that esophagography is also accurate in either diagnosing or excluding the disorder. Accordingly, we compared the efficacy of esophagography and HREM in diagnosing achalasia patients with upper gastrointestinal symptoms. METHODS: HREM was performed in 126 patients with dysphagia. The final diagnosis of achalasia was done using HREM. Demographic data, symptoms, quality of life (QOL) were also obtained. We assessed the patients who were not able to be diagnosed by esophagography and compared the diagnostic values for esophagography with HREM-based achalasia diagnosis as the gold standard. RESULTS: A total of 48 cases of patients with achalasia, including 21 men and 27 women (mean age, 48.4 ± 19.6 years), were included in the study. Two patients were excluded. Of the remaining 46 patients, 36 (78.3%) patients were diagnosed as having achalasia by esophagography. The diagnostic sensitivity, specificity, and accuracy of esophagography were 78.3%, 88.0%, and 83.0%, respectively. Patients with type III achalasia had significantly lower physical QOL score than those with type I or II achalasia. Although the mental QOL score in patients with type III achalasia tended to decrease compared with that in patients with type I and II achalasia, the difference was not statistically significant. CONCLUSIONS: Diagnosing esophageal achalasia by using esophagography alone has limited yield. Therefore, HREM should be used in patients with dysphagia and in whom achalasia cannot be diagnosed using EGD or esophagography.

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95% CI: 0.06-0.41, p = 0.0002), but was less effective in reversing the methylation that occurred in IM. Frequent hypermethylation including that of CDH1 in AM increased in the GC group compared to the AG group, and CDH1 methylation was an independent predictive marker of GC (OR: 8.50, 95% CI: 2.64-25.33, p = 0.0003). In patients with long-term aspirin use, the changes of molecular events in AM but not IM may be an important factor in the reduction of cancer incidence. In addition, methylation of the CDH1 gene in AM may be a surrogate of GC.

Reflux Hypersensitivity: A New Functional Esophageal Disorder.

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.

Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals.

BACKGROUND/AIMS: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. METHODS: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. RESULTS: When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P 〈 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P 〈 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P 〈 0.01) and 60 minutes (20.3 ± 6.7 minutes, P 〈 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. CONCLUSION: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.