Ann Ouyang

Pneumatic Dilatation or Esophagomyotomy Treatment for Idiopathic Achalasia: Clinical Outcomes and Cost Analysis

The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7±2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy, (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age≥45, years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients <45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with penumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward, surgery.

Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma

Gastroesophageal reflux is well documented in scleroderma, but the complications of Barretts metaplasia and adenocarcinoma are not well described. The records of 75 patients with scleroderma seen over a four-year period at the Hospital of the University of Pennsylvania were retrospectively reviewed to determine the prevalence of Barretts metaplasia and adenocarcinoma of the esophagus and to identify clinical, manometric, laboratory, or radiographic criteria that might predict the presence of these lesions. Twenty-four of these patients underwent endoscopy. In this group, the prevalence of Barretts metaplasia was 37 percent (nine patients) and adenocarcinoma was also present in two of these patients. The patients with and without Barretts metaplasia were similar in age (range, 22 to 64 compared with 28 to 79, respectively), sex (six of nine compared with 12 of 15 female, respectively), frequency of esophageal motility disorders, presence of proximal skin involvement, digital ulceration, and pulmonary involvement as measured by diffusion capacity. Barretts metaplasia was diagnosed on the basis of double-contrast esophagographic results in only one of eight patients with Barretts metaplasia so-studied. Patients with Barretts metaplasia tended to have longer duration of heartburn (90 +/- 40 months compared with 11 +/- 35 months) and dysphagia (39 +/- 22 months compared with 7 +/- 3 months). Patients with Barretts metaplasia also tended to have greater impairment of lower esophageal sphincter pressure either at end-expiration (4.0 +/- 2.1 compared with 6.1 +/- 1.8 mm Hg) or mid-respiration (13.0 +/- 3.0 compared with 16.9 +/- 2.5 mm Hg). Using chi-square analysis, however, none of these differences reached statistical significance. Discrimination did occur on the basis of the presence of the CREST (calcinosis, Raynauds phenomenon, esophageal manifestations of scleroderma, sclerodactyly, and telangiectasis) variant (55 percent compared with 7 percent, p less than 0.01), a duration of dysphagia of more than five months (p less than 0.03), and mid-respiratory lower esophageal sphincter pressure of less than 10 mm Hg (p less than 0.05). It is suggested that: Barretts metaplasia of the esophagus occurs in one third of patients with scleroderma; clinical, manometric, laboratory, and radiographic features are poor predictors of the presence of Barretts metaplasia; patients with CREST syndrome, prolonged dysphagia, or a very low lower esophageal sphincter pressure may have an increased risk for the development of metaplasia; patients with scleroderma and Barretts metaplasia have an increased risk of complications such as stricture or adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Nitric Oxide Synthase (NOS) Expression in the Myenteric Plexus of Streptozotocin-Diabetic Rats

Nitric oxide (NO) is an important inhibitoryneurotransmitter in the gut. Alterations in NO mediatedresponses have been described in diabetic animals. Thepresence of nitric oxide synthase (NOS) reflects the potential for NO synthesis and is found inneurons in the myenteric plexus. The aim of this studywas to determine changes in nitric oxide synthase (NOS)expression in the myenteric plexus of thegastrointestinal tract of diabetic rats at three months ofstreptozotocin-induced diabetes, compared to age matchedcontrols, using immunohistochemistry. Diabetic animalsshowed a decrease in NOS expression in the antrum, with 59.1 ± 7.3% of neurons beingpositive for NOS in diabetes compared to 81.2 ±4.7% in controls (P < 0.05). NOS expression induodenum, ileum, and colon of diabetic animals was notstatistically different from controls. Decreased expression of NOS inantrum may contribute to altered gastric emptyingobserved in diabetics.

Esophageal chest pain: value of high-dose provocative testing with edrophonium chloride in patients with normal esophageal manometries

The unequivocal diagnosis of esophageal chest pain requires the demonstration of simultaneous manometric changes and chest pain. Numerous provocative agents have been used to enhance the diagnostic value of esophageal manometry. Our aims were to: (1) evaluate consecutively a large group of patients with proven noncardiac chest pain and normal baseline manometric studies, using edrophonium chloride, 10 mg, and (2) determine the value of provocative testing in clinical practice. One hundred twenty patients with normal standard baseline esophageal manometries were studied using blinded testing with edrophonium chloride and followed clinically by questionnaire. A positive response of both chest pain and manometric changes was observed in 34%, a negative response in 49%, and an indeterminate response in 17% of patients. Baseline manometric features, including high-amplitude contractions, did not predict the response to edrophonium chloride. Following edrophonium chloride administration, the change in amplitude, duration, and number of repetitive contractions from baseline was significantly greater in positive responders. Edrophonium decreased the velocity of propagated contractions in positive responders (P<0.05), but not in nonresponders. Response to edrophonium chloride could not be predicted by patient age, sex, or clinical symptomatology. Seventy percent of patients in both groups had symptoms indistinguishable from ischemic heart disease. After making a specific diagnosis of esophageal chest pain, patients showed a marked clinical improvement, with a significant decrease in physical limitation, emergency room visits, hospital and CCU admissions, and in further cardiac testing. We conclude that provocative testing with edrophonium chloride will make it possible to definitively implicate the esophagus in over 30% of patients with normal baseline manometric findings and noncardiac chest pain.

Complications during pneumatic dilation for achalasia or diffuse esophageal spasm : analysis of risk factors, early clinical characteristics, and outcome

A retrospective cohort study was performed to assess risk factors, early clinical characteristics, and outcome of complications in patients undergoing pneumatic dilation. Of 178 patients with achalasia or diffuse esophageal spasm who underwent 236 dilations with a Browne-McHardy dilator, 16 patients experienced a complication (9.0%). Nine major complications developed: perforations (4), hematemesis (2), fever (2), and angina (1). A prior pneumatic dilation and use of inflation pressure ≥11 PSI were independent risk factors by multivariate analysis for developing a complication. An esophagram immediately following the dilation identified three of the four perforations. Three postdilation findings were identified as indicators of patients with an increased risk of having developed a perforation: blood on the dilator, tachycardia, and prolonged chest pain lasting >4 hr after dilation. In all patients incurring a major complication, one of the three indicators, or the complication itself was recognized within 5 hr of dilation. All patients with complications, including the four with perforation who received prompt surgical repair and esophagomyotomy, recovered uneventfully. The symptomatic relief of dysphagia in patients with perforation undergoing emergent surgical repair and esophagomyotomy was similar to patients undergoing elective esophagomyotomy. Conclusions: (1) Pneumatic dilation is a safe treatment of achalasia, with a 1.7% risk of perforation. (2) The risk of developing a complication is increased by having had a previous pneumatic dilation or by use of inflation pressures ≥11 psi. (3) All patients with a major complication were identified within 5 hr after dilation. (4) Complications following pneumatic dilation, if recognized and treated promptly, were not associated with adverse, long-term sequelae.

Chronic severe constipation

The purpose of this study was to determine the patterns of gastrointestinal and anal sphincter motility in 25 consecutive patients with severe constipation. Three patterns of abnormal motility were observed in 68% of the patients: (a) isolated anal sphincter dysfunction (20%), (b) a generalized disorder of gastrointestinal motility [24%){ and [c) rectosigmoid dysfunction (24%). The remaining patients had either a previously unrecognized primary disorder leading to constipation or the irritable bowel syndrome. Duration of symptoms, laxative usage, or other historical features failed to distinguish each of the groups. Anal sphincter dysfunction was diagnosed by demonstrating impaired sphincter relaxation during rectal distention. Generalized motor disorders were diagnosed by demonstrating impaired colonic and esophageal function together with an abnormality in gastric emptying. Rectosigmoid dysfunction was manifest by an impaired rectosigmoid motor response to feeding without evidence of other organ dysfunction. These studies indicate that a high percentage of patients with more severe degrees of constipation have a serious but sometimes treatable disorder of bowel function, rather than the irritable bowel syndrome.

Pneumatic dilatation in patients with symptomatic diffuse esophageal spasm and lower esophageal sphincter dysfunction

Nine patients with severe symptoms of diffuse esophageal spasm and lower esophageal sphincter dysfunction who were unresponsive to medical therapy and bougienage dilatation were treated by forceful pneumatic dilatation. Treatment with pneumatic dilatation in eight of the nine patients produced a marked improvement in dysphagia and regurgitation (average follow-up of 37.4 months). Esophageal motility performed up to three years (average 12.4 months) after clinically successful pneumatic dilatation revealed a decrease in lower esophageal sphincter pressure from 34.0±4.0 mmHg (mean ± standard error) to 19.2±2.7 mm Hg (P<0.01). There were no significant changes in either the percentage of lower esophageal sphincter relaxation or the type of esophageal motor pattern. We conclude from this study that pneumatic dilatation is an effective form of therapy for a select group of patients with severe symptomatic diffuse esophageal spasm with lower esophageal sphincter dysfunction who are unresponsive to conventional medical therapy.

Caloric content of a meal affects duration but not contractile pattern of duodenal motility in man

The variability of the fasted duodenal contractile pattern and the patterns of contraction during the fed phase was examined in normal volunteers. Prolonged recordings from the duodenum and proximal jejunum were achieved using a series of transducers mounted on a 2.3-mm catheter. A total of 58 interMMC intervals and the response to 18 meals was examined. There was marked inter- and intrasubject variability in the fasted state, even within one study. The phase II pattern was examined in detail and propagated single peaks, propagated clusters, and repeated propagated clusters are described. Single peaks could be propagated as rapidly as 16 cm/sec. Single peaks were propagated more rapidly than propagated multiple peaks. During phase III, duodenal contractions occurred at 11.3 ±0.09/min and jejunal contractions at 10.73±0.15/min. The rate of progression of the onset of phase III was 0.145±0.015 cm/sec. The effect of the caloric content of the meal was examined by determining the effect of 150-kcal, 300-kcal, and 600-kcal meals on the fed pattern. Increasing caloric content increased the duration of the fed pattern but had no effect on the total or normalized motility index or on the change in motility index over time during the fed pattern. The types of contractions seen during the fed pattern are described. Propagated clusters over at least 16 cm are common during the fed phase in normals, with 10% of all contractions seen during the fed phase being propagated over 28 cm. No difference in the patterns of contractions or their propagation was seen with the different caloric contents of the meals. These studies demonstrate the variability of the normal fasted pattern and demonstrate the motor equivalents of a variety of myoelectric patterns that have been described. A method of analyzing the fed pattern is described.

TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus

Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus.

Contribution of Gender to Pathophysiology and Clinical Presentation of IBS: Should Management Be Different in Women?

The irritable bowel syndrome (IBS) is found more commonly in women than men. It is more prevalent in patients with chronic fatigue syndrome, fibromyalgia, and chronic pelvic pain, all syndromes characterized by pain and found predominantly in women. This article reviews evidence for a role of biological sex factors and gender on the pathways mediating visceral pain. The effect of gonadal hormones on gastrointestinal motility and the sensory afferent pathway and central processing of visceral stimuli and the contribution of gender role to the clinical presentation are discussed. Although differences in responses to treatment modalities between genders exist, the approach to IBS patients in both genders is quite similar. Nevertheless, a special attention to gender role and stress-related factors should be addressed. New developments in research, outlined in the paper, might bring more gender-specific treatments in the future.