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Biomedical subjects

Stuart Jon Spechler

Publications and source records attributed to Stuart Jon Spechler.

At least 19 recordsLinked to original sources
PubMed2006

High-frequency probe ultrasonography has limited accuracy for detecting invasive adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma: a case series.

AIM: To evaluate prospectively the accuracy of preoperative high-frequency (20 MHz) probe ultrasonography (HFPUS) for detecting invasive cancer in patients referred for esophagectomy because of an endoscopic biopsy diagnosis of high-grade dysplasia (HGD) or intramucosal carcinoma (ICA) in Barrett's esophagus (BE). PATIENTS AND METHODS: Nine consecutive male patients (median age of 69 yr) who were referred for esophagectomy for HGD or ICA in BE agreed to participate. We performed conventional upper gastrointestinal endoscopy followed by HFPUS using a through-the-scope ultrasound probe (20 MHz), and we compared our preoperative findings with the pathologist's findings in the resected esophageal specimens. RESULTS: There was complete agreement between the postoperative pathological findings and the preoperative HFPUS findings in only 4 of the 9 patients. HFPUS resulted in two false-negative diagnoses of esophageal cancer (both had T1 lesions in the resected specimens), one false-positive diagnosis of esophageal cancer, and two errors in tumor staging (1 understaged, 1 overstaged). CONCLUSIONS: HFPUS has limited accuracy for identifying invasive cancer in patients found to have HGD or IMC in BE. Pending further refinements in technology, clinical management decisions in such patients should not be based solely on the results of HFPUS.

Adenocarcinoma↗
PubMed2006

Upper gastrointestinal bleeding in a patient with AIDS.

BACKGROUND: A 38-year-old man with AIDS and hepatitis C was admitted to our hospital in January 2005, with complaints of epigastric pain, odynophagia, and melena of 4 days' duration. The patient was not taking highly active antiretroviral therapy because of poor compliance and he denied use of NSAIDs. INVESTIGATIONS: Physical examination, stool guaiac test, laboratory investigations, and esophagogastroduodenoscopy with biopsies of gastric ulcerations. DIAGNOSIS: Non-Hodgkin's lymphoma of the stomach (diffuse large B-cell type) with associated gastric ulceration and bleeding. MANAGEMENT: Injection of epinephrine and bipolar coagulation for the bleeding malignant ulcer, and PPI therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Barrett's esophagus: a molecular perspective.

Carcinogenesis in Barrett's esophagus involves the accumulation of DNA abnormalities that enable cells to 1) provide their own growth signals; 2) ignore growth-inhibitory signals; 3) avoid apoptosis; 4) replicate without limit; 5) sustain angiogenesis; and 6) invade and proliferate in unnatural locations. This report reviews recent publications describing molecular abnormalities in Barrett's esophagus that could lead to the acquisition of these key physiologic hallmarks of malignancy. Some recent reports suggest that the gastroesophageal reflux of acid and bile can activate molecular pathways that promote proliferation and interfere with apoptosis in Barrett's metaplastic cells. Inactivation of the p16 and p53 tumor suppressor genes through promoter methylation, gene mutation, or loss of heterozygosity appears to be important for carcinogenesis in Barrett's esophagus. Finally, this report discusses recent data regarding the role of the Cdx2 gene in the development of esophageal intestinal metaplasia.

Apoptosis↗
PubMed2005

Dysplasia in Barrett's esophagus: limitations of current management strategies.

Dysplasia is a very imperfect biomarker for malignancy in Barrett's esophagus. Invasive cancer has been found in 30-40% of esophagi resected because preoperative endoscopic examinations had shown high-grade dysplasia. Reports on the natural history of this disorder are sometimes contradictory, but suggest that 10-30% of patients with high-grade dysplasia in Barrett's esophagus will develop a demonstrable malignancy within 5 yr of the initial diagnosis. Proposed management strategies for high-grade dysplasia include esophagectomy, endoscopic ablative therapies, endoscopic mucosal resection (EMR), and intensive endoscopic surveillance. Endoscopic ablative therapies and EMR may not be effective if neoplastic cells have invaded the submucosa or disseminated through mucosal lymphatic channels, and a number of studies suggest that the endoscopic therapies usually leave metaplastic or neoplastic epithelium with malignant potential behind. Limited data suggest that intensive endoscopic surveillance might be a reasonable approach for elderly or infirm patients, but some patients managed in this fashion have developed incurable esophageal cancers. The fundamental question of what is the appropriate length of follow-up for studies on dysplasia treatments has not been resolved. Although 5 yr might be considered the absolute minimum duration for a meaningful follow-up on dysplasia therapy, the follow-up duration in most studies is substantially less than 5 yr. Specific recommendations for management based on these considerations are proposed at the end of this report.

Adenocarcinoma↗
PubMed2004

The management of patients who have "failed" antireflux surgery.

Gastroenterologists may be called upon to manage patients who have had antireflux surgery that failed. The available literature on this topic comprises predominantly reports on retrospective, observational studies written by surgeons who often have focused on how technical deficiencies in performing the operation led to the failure. Such reports are of limited value to the gastroenterologist seeking guidance on patient management. Furthermore, comparisons among the reports are confounded by the lack of a standardized definition for failed antireflux surgery. This report critically reviews the available literature, and suggests a practical approach to the management of patients who have symptoms that were not completely relieved, that reappeared later, or that were caused by antireflux surgery.

Deglutition Disorders↗
PubMed2004

Re-examination of the cost-effectiveness of surgical versus medical therapy in patients with gastroesophageal reflux disease: the value of long-term data collection.

OBJECTIVES: For patients with reflux esophagitis, long-term therapeutic options include proton pump inhibitor (PPI) therapy and/or antireflux surgery. An earlier cost-effectiveness analysis concluded that at 5 yr, medical therapy was less expensive but similarly effective to fundoplication, but the results were sensitive to estimates on quality of life and long-term medication usage, which were derived from "expert opinion." Recently, data from randomized controlled trials addressing these variables have become available. We have incorporated these new data into a revised Markov model to examine the cost-effectiveness of surgical versus medical therapy in patients with severe reflux esophagitis. METHODS: A Markov simulation model was constructed using specialized software (DATA PRO 4.0, Williamstown, MA). Total expected costs and quality-adjusted life-years were calculated for long-term medical therapy and for laparoscopic Nissen fundoplication. Probabilities were obtained from the medical literature using Medline. Procedural and hospitalization costs used were the average Medicare reimbursements at our institution. Medication costs were the average wholesale price. The analysis was extended over a 10-yr time horizon at a discount rate of 3%. RESULTS: The discounted analysis shows that medical therapy is associated with total costs of 8,798 dollars and 4.59 quality-adjusted life-years, whereas the surgical strategy is more expensive (10,475 dollars) and less effective (4.55 quality-adjusted life-years). The results were robust to most one-way sensitivity analyses. CONCLUSIONS: Long-term medical therapy with proton pump inhibitors is the preferred strategy for patients with gastroesophageal reflux disease and severe esophagitis. Our study highlights the importance of using primary, patient-derived data rather than expert opinion.

Analysis of Variance↗
PubMed2004

Irreversible ototoxicity associated with difluoromethylornithine.

Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m(2)/d, and generally when the cumulative dose exceeds 250 g/m(2). In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and a > or =20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m(2)/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m(2)). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk.

Antineoplastic Agents↗
PubMed2003

Esophageal complications of gastroesophageal reflux disease: presentation, diagnosis, management, and outcomes.

The esophageal complications of gastroesophageal reflux disease include peptic esophageal erosion and ulceration, peptic esophageal strictures, and Barrett's esophagus. Endoscopy is the diagnostic procedure of choice for the initial evaluation of lesions. For most patients, symptoms can be controlled with proton pump inhibitor (PPI) therapy. PPIs are also highly effective for healing esophageal erosions and ulcerations and for preventing recurrence of peptic esophageal strictures. Because Barrett's esophagus predisposes individuals to esophageal adenocarcinoma, these patients are advised to have regular endoscopic surveillance to detect early, curable neoplasms.

Barrett Esophagus↗
PubMed2003

Medical or invasive therapy for GERD: an acidulous analysis.

This review critically appraises the evidence on the benefits and costs of the available treatments for gastroesophageal reflux disease (GERD) and concludes that antireflux surgery has no clear advantages over medical therapy for efficacy of healing, prevention of complications, safety, side effects, and cost. Indeed, medical therapy is safer and, probably, more cost-effective. Compared with medically treated patients, those who have successful fundoplication may be less inconvenienced by GERD because they are less likely to need to take pills on a daily basis. The patient and physician must judge whether that benefit justifies the risks of surgery for a benign condition. There is not yet sufficient data available on the endoscopic antireflux procedures to make meaningful conclusions regarding their safety and efficacy.

Adenocarcinoma↗
PubMed2003

Clinical manifestations and esophageal complications of GERD.

This report focuses on the manifestations of gastroesophageal reflux disease (GERD) that are caused directly by contact between refluxed gastric juice and the esophageal mucosa. These manifestations include heartburn, peptic esophageal erosion and ulceration, peptic esophageal stricture, and Barrett esophagus. Peptic esophageal erosions and ulcerations are excavated defects in the esophageal mucosa that result when epithelial cells succumb to the caustic effects of refluxed acid and pepsin. Uncommonly, esophageal ulcers are complicated by hemorrhage, perforation, and penetration into the airway. Esophageal ulcers can stimulate fibrous tissue production and collagen deposition that result in stricture formation, and the ulcers can heal through a metaplastic process in which an intestinal-type epithelium replaces the damaged squamous cells (Barrett esophagus). The management of these conditions is discussed below.

Animals↗
PubMed2003

Intestinal metaplasia at the gastroesophageal junction: Barrett's, bacteria, and biomarkers.

For patients found to have intestinal metaplasia at the gastroesophageal junction, technical problems can make it difficult to distinguish short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Whereas the risk of malignancy for the former condition seems to be higher than that for the latter, the distinction between these conditions can have practical clinical implications. Immunostaining for cytokeratins has been proposed as a means to distinguish intestinal metaplasia of esophageal and gastric origins. We review recent data on this issue, and conclude that immunostaining for cytokeratins has no clear advantages over other biomarkers that have been proposed for identifying Barrett's esophagus (e.g., mucin histochemistry, mAb Das-1 immunoreactivity). Presently, the importance of intestinal metaplasia at the gastroesophageal junction remains unclear, and the clinical utility of biomarkers in distinguishing short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia has not yet been established.

Bacteria↗
PubMed2002

Barrett's esophagus and esophageal adenocarcinoma: pathogenesis, diagnosis, and therapy.

Gastric juice that refluxes into the esophagus can injure esophageal squamous epithelium. When the injury heals through a metaplastic process in which an abnormal columnar epithelium replaces the injured squamous one, the resulting condition is called Barrett's esophagus. Gastroesophageal reflux disease and Barrett's esophagus are the most important risk factors for esophageal adenocarcinoma. This article examines such issues as the treatment, endoscopic surveillance, and chemoprevention of Barrett's esophagus. Also included are published guidelines and recommendations.

Adenocarcinoma↗