Howard Mertz

Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention

BACKGROUND & AIMS Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. METHODS fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. RESULTS Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls. CONCLUSIONS IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.

Symptoms and visceral perception in severe functional and organic dyspepsia

Background—Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia. Aims—To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their perception of gastric distension and whether this difference is reflected in differences in their gastrointestinal and psychological symptoms. Methods—Perceptual thresholds, referral patterns, and gastrointestinal and psychological symptoms were compared in 23 patients with functional dyspepsia, 10 organic dyspeptics, and 15 healthy controls. Results—Fifteen (65%) functional dyspeptics and no organic dyspeptics had reduced perceptual thresholds for fullness, discomfort, or pain (odds ratio (OR) 19.56, 95% confidence interval (CI) 1.95 to 476.09, p=0.0017). Either reduced perceptual thresholds or altered referral was found in 20 (87%) functional dyspeptics and four (20%) organic dyspeptics (OR 10.0, 95% CI 1.34 to 89.54, p=0.014). During sham distension fullness, discomfort and pain were reported by healthy controls, organic dyspeptics, and functional dyspeptics. A sham response of pain but no other sensation was more frequent among functional dyspeptics (43%) than healthy controls (7%) (OR 10.77, 95% CI 1.10 to 257.35, p=0.026). Gastrointestinal and psychological symptoms and gastric compliance were similar in the functional and organic groups. Conclusions—Alterations in the perception of gastric distension distinguishes between functional and organic dyspepsia, while symptoms do not. A total of 87% of functional dyspeptics studied had evidence of altered visceral afferent function. In this study population, psychological abnormalities or changes in compliance did not explain the findings.

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome

Background and aims: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Methods: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Results: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. Conclusions: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

Symptoms and physiology in severe chronic constipation

Objective: Symptoms of constipation have been attributed to slow colon transit, irritable bowel syndrome (IBS), or pelvic floor dysfunction (PFD). Our aim was to determine the existence of symptom-based constipation subgroups and whether these correspond to differences in colonic transit and anorectal sensorimotor function. Methods: Constipated patients (n = 108) completed questionnaires, and underwent colon transit studies, anorectal manometry, and rectal sensory testing. Factor analysis of symptoms was performed. Factor-based symptom scores were correlated with physiological findings. Results: Three symptom factors were identified as compatible with slow colonic transit, IBS, and PFD. There was a significant correlation between the symptoms of slow transit and total and rectosigmoid colon transit. There were also significant correlations between both the IBS symptom score and the number of Manning criteria with measures of rectal hypersensitivity typical of IBS. Neither PFD symptom scores nor symptoms of straining correlated with any electromyographic or manometric measure of anal defecatory function or with rectosigmoid colon transit. Based on physiological testing patients were classified as slow transit, visceral hypersensitivity (typical of IBS), PFD, or no abnormalities found. As expected, slow-transit patients had symptoms of infrequent stools and patients with visceral hypersensitivity had an increased number of Manning criteria for IBS. Patients with PFD physiology and those with no detectable abnormalities had no specific symptoms. Conclusions: Three symptom-based subgroups for constipation were confirmed: slow transit, IBS, and PFD. Slow transit and IBS symptoms correlated with expected physiology. Conversely, PFD symptoms and physiology did not correlate.

Methylene Blue Staining and Endoscopic Ultrasound Evaluation of Barrett's Esophagus with Low-Grade Dysplasia

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barretts esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 ± 0.2 mm), nondysplastic Barretts (2.6 ± 0.2 mm), and Barretts with dysplasia (2.9 ± 0.3 mm) were similar. With staining, Barretts mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barretts were 68% and 85%, respectively. Barretts with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barretts (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.

Validation of a new measure of diarrhea

Adequate measures of diarrheal disease are important to assess severity for clinical use and outcomes research. We developed a questionnaire to assess diarrhea severity and complications, and administered it to 205 HIV positive patients with diarrhea, fever, or weight loss. Noteworthy variations in stool form were reported by individuals and across subjects. Self-reported diarrhea correlated with the occurrence of any stool picture without form. However, verbal descriptors “loose” and “semiformed” had little value in assessment of diarrheal disease. Both verbal and pictorial stool descriptors correlated well with diarrhea complications (pain, urgency, tenesmus, incontinence, and nocturnal diarrhea). By factor analysis, discomfort and nondiscomfort diarrhea complications loaded on different factors, consistent with clinical experience that discomfort is a distinct problem in diarrheal disease. In summary we have developed an instrument to precisely characterize diarrhea severity that correlates well with clinically important events such as incontinence and abdominal pain.

Overview of functional gastrointestinal disorders: dysfunction of the brain-gut axis

Functional gastrointestinal disorders are common and incompletely understood. The gut is controlled by a complex interaction of sensory and motor neurons in the local enteric nervous system. Inputs from the central nervous system modify gut function, whereas inputs from the gut to the brain mediate symptoms. Dysfunction at one or more sites in the brain-gut axis is likely to produce the various functional gastrointestinal syndromes. Therapies likewise can be directed at one or more levels.

Gastric metaplasia of the duodenum: identification by an endoscopic selective mucosal staining technique☆☆☆★

BACKGROUND To understand the pathophysiology of duodenal ulcer disease, it is important to identify and quantitate gastric metaplasia of the duodenum. Methylene blue dye is absorbed well by intestinal mucosa, but not by gastric mucosa. Our aim was to validate a methylene blue staining technique for measurement of gastric metaplasia in the duodenum. METHODS Eight subjects with chronic duodenal ulcer disease and seven subjects with other upper intestinal disorders underwent duodenal methylene blue staining after application of a mucolytic agent. Biopsy specimens were obtained from blue-stained and pale unstained areas and assessed for gastric metaplasia histologically. RESULTS Pink or pale unstained duodenal areas had more gastric surface cell metaplasia than blue-stained areas. Unstained duodenum was also more likely to have extensive (more than 25% of the biopsy specimens) gastric metaplasia (60%) than blue-stained areas (9%). Subjects with duodenal ulcer disease had more unstained mucosa than controls. CONCLUSION Methylene blue staining of the duodenum is useful to identify and quantitate gastric metaplasia.

Dysplastic gastroesophageal junction nodules : A precursor to junctional adenocarcinoma

ABSTRACTAdenocarcinoma of the gastroesophageal junction is a disease rapidly increasing in prevalence. The origin of these tumors is unclear. Barretts esophagus, gastric cardia lesions, and mucus glands of the distal esophagus have been implicated. This case report presents two cases of patients who had chest pain leading to esophagogastroduodenoscopy. Both had small, benign-appearing nodules at the gastroesophageal junction in the absence of Barretts esophagus or gastric lesions. Biopsies revealed intestinal metaplasia with dysplasia in one patient and dysplasia of the mucus glands of the esophagus in the other. The first patient was followed for 8 months with serial biopsies, during which time the lesion became progressively more dysplastic, culminating in invasive cancer. These cases are presented to show that 1) benign-appearing gastroesophageal junction nodules may have malignant behavior, and 2) junctional cancer and high grade dysplasia can occur in the absence of Barretts esophagus or gastric cardia lesions. Gastroesophageal junctional dysplasia/carcinoma may occur in small foci of intestinal metaplasia or in the mucus glands of the distal esophagus.

CASE REPORT: Eosinophilic Gastroenteritis Causing Pancreatitis and Pancreaticobiliary Ductal Dilation

Eosinophilic gastroenteritis (EGE), an uncommon disorder, was first described by R. Kaijser in 1937 (1). The disease is manifest by peripheral eosinophilia and a variable eosinophilic infiltration of the bowel wall. Clinical symptoms are dependent on the depth and site of infiltration. Biliary obstruction has been reported in only three cases (2–4), and to date there is only one report of pancreaticobiliary obstruction (5) from duodenal infiltration. The extent of eosinophilic infiltration is usually not limited to the duodenum, but it is there that most symptoms are thought to originate. We report a case of partial biliary and pancreatic duct obstruction due to eosinophilic gastroenteritis manifested by abdominal pain, nausea, weight loss, and pancreatitis. This is the first published report of pancreatitis due to EGE. We discuss the pathology of EGE and review the relevant literature.