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Biomedical subjects

T R DeMeester

Publications and source records attributed to T R DeMeester.

At least 37 records · Page 2Linked to original sources

Gastro-esophageal reflux disease confined to the sphincter.

It has been shown previously that patients with gastro-esophageal reflux disease (GERD) do not always have increased esophageal acid exposure on 24 h pH monitoring. The recent recognition of carditis as a sensitive marker for GERD raises the possibility for patients with mild disease to have normal esophageal acid exposure but inflamed cardiac mucosa on biopsies of the cardia, which may be an early sign of GERD. To test this hypothesis, 171 consecutive patients evaluated for symptoms of GERD and no increased esophageal acid exposure, Barrett's esophagus or erosive esophagitis were divided into those with and without carditis. Esophageal acid exposure and lower esophageal sphincter (LES) characteristics were compared between the two groups. Comparisons were done using the Mann-Whitney U-test for non-parametric data. There were 82 patients with histologic evidence of carditis and 89 patients without carditis. Patients with carditis had a more deteriorated sphincter, determined by overall and abdominal length and resting pressure, and significantly higher esophageal acid exposure (P < 0.05). Patients with symptoms of GERD and histologic evidence of carditis may have early or mild reflux disease, which is confined to the sphincter.

Adolescent↗

DNA methylation: an alternative pathway to cancer.

OBJECTIVE: To provide an introduction to the concept of DNA methylation and its function in normal cells, and to explain the possible mechanisms as to how abnormalities in this phenomenon can relate to carcinogenesis. The clinical implications with reference to common malignancies encountered in surgical practice are discussed. SUMMARY BACKGROUND DATA: Methylation of DNA is a heritable, enzyme-induced modification to DNA structure without alteration of the specific sequence of the base pairs responsible for encoding the genome. DNA methylation can both directly inhibit the expression of genes and also increase the probability that affected genes undergo a mutational event. Although DNA methylation plays an essential role in normal biologic processes, distinct and abnormal patterns of methylation are observed in cancers. In particular, there has been increased documentation that methylation of the promoter regions of several genes, including known tumor suppressor genes, results in the subsequent failure to express their functional proteins. Consequently, DNA methylation may represent an early and fundamental step in the pathway by which normal tissue undergoes neoplastic transformation. Further, an assessment of the methylation profiles within neoplastic tissues may provide key information in enhancing the diagnosis, predicting the clinical behavior, and designing specific treatment plans for individual patients. METHODS: Published literature from 1925 to 2000 contributing to an understanding of the purpose of DNA methylation and how pathology of this phenomenon could contribute to cancer are reviewed. Theories on these issues and the evidence that led to them are described. The present status of the subject in a clinical context is discussed. RESULTS: Gene expression can be significantly modulated by alterations in DNA methylation patterns. Methylation within the promoter regions of tumor suppressor genes causes their silencing, and methylation within the gene itself can induce mutational events. These mechanisms may play a fundamental role in precipitating the development of a large and diverse number of human cancers. CONCLUSIONS: DNA methylation is an important factor in the development of cancer. A greater understanding of the relationship between DNA methylation events at the molecular level and its interaction in the clinical context may provide the basis for future advances in the surgical and pharmacologic management of malignant diseases.

Breast Neoplasms↗

Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies.

OBJECTIVE: To document what can be accomplished with surgical resection done according to the classical principles of surgical oncology. METHODS: One hundred consecutive patients underwent en bloc esophagectomy for esophageal adenocarcinoma. No patient received pre- or postoperative chemotherapy or radiation therapy. Tumor depth and number and location of involved lymph nodes were recorded. A lymph node ratio was calculated by dividing the number of involved nodes by the total number removed. Follow-up was complete in all patients. The median follow-up of surviving patients was 40 months, with 23 patients surviving 5 years or more. RESULTS: The overall actuarial survival rate at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC) stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%; stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were transmural. Tumor depth and the number and ratio of involved nodes were predictors of survival. Metastases to celiac (n = 16) or other distant node sites (n = 26) were not associated with decreased survival. Local recurrence was seen in only one patient. Latent nodal recurrence outside the surgical field occurred in 9 patients and systemic metastases in 31. Tumor depth, the number of involved nodes, and the lymph node ratio were important predictors of systemic recurrence. The surgical death rate was 6%. CONCLUSION: Long-term survival from adenocarcinoma of the esophagus can be achieved in more than half the patients who undergo en bloc resection. One third of patients with lymph node involvement survived 5 years. Local control is excellent after en bloc resection. The extent of disease associated with tumors confined to the mucosa and submucosa provides justification for more limited and less morbid resections.

Adenocarcinoma↗

Long-term outcome of antireflux surgery in patients with Barrett's esophagus.

OBJECTIVE: To assess the long-term outcome of antireflux surgery in patients with Barrett's esophagus. SUMMARY BACKGROUND DATA: The prevalence of Barrett's esophagus is increasing, and its treatment is problematic. Antireflux surgery has the potential to stop reflux and induce a quiescent mucosa. Its long-term outcome, however, has recently been challenged with reports of poor control of reflux and the inability to prevent progression to cancer. METHODS: The outcome of antireflux surgery was studied in 97 patients with Barrett's esophagus. Follow-up was complete in 88% (85/97) at a median of 5 years. Fifty-nine had long-segment and 26 short-segment Barrett's. Patients with intestinal metaplasia of the cardia were excluded. Fifty patients underwent a laparoscopic procedure, 20 a transthoracic procedure, and 3 abdominal Nissen operations. Nine had a Collis-Belsey procedure and three had other partial wraps. Outcome measures included relief of reflux symptoms (all), patients' perception of the result (all), upper endoscopy and histology (n = 79), and postoperative 24-hour pH monitoring (n = 21). RESULTS: At a median follow-up of 5 years, reflux symptoms were absent in 67 of 85 patients (79%). Eighteen (20%) developed recurrent symptoms; four had returned to taking daily acid-suppression medication. Seven patients underwent a secondary repair and were asymptomatic, increasing the eventual successful outcome to 87%. Recurrent symptoms were most common in patients undergoing Collis-Belsey (33%) and laparoscopic Nissen (26%) procedures and least common after a transthoracic Nissen operation (5%). The results of postoperative 24-hour pH monitoring were normal in 17 of 21 (81%). Recurrent hiatal hernias were detected in 17 of 79 patients studied; 6 were asymptomatic. Seventy-seven percent of the patients considered themselves cured, 22% considered their condition to be improved, and 97% were satisfied. Low-grade dysplasia regressed to nondysplastic Barrett's in 7 of 16 (44%), and intestinal metaplasia regressed to cardiac mucosa in 9 of 63 (14%). Low-grade dysplasia developed in 4 of 63 (6%) patients. No patient developed high-grade dysplasia or cancer in 410 patient-years of follow-up. CONCLUSIONS: After antireflux surgery, most patients with Barrett's enjoy long-lasting relief of reflux symptoms, and nearly all patients consider themselves cured or improved. Mild symptoms recur in one fifth. Importantly, dysplasia regressed in nearly half of the patients in whom it was present before surgery, intestinal metaplasia disappeared in 14% of patients, and high-grade dysplasia and adenocarcinoma were prevented in all.

Adolescent↗

The crura and crura-sphincter pressure dynamics in patients with isolated upright and isolated supine reflux.

The reason why patients with isolated supine reflux do not reflux in the upright position and patients with isolated upright reflux do not reflux in the supine position is unknown. Our objective was to determine the characteristics of the crura, lower esophageal sphincter, crura-sphincter dynamics, and esophageal body on manometry, endoscopy, and X-ray in patients with isolated upright and isolated supine reflux. Eighty consecutive patients with isolated upright reflux were compared with 82 consecutive patients with isolated supine reflux. Manometrically there was no difference in lower esophageal sphincter characteristics and esophageal contractions between the two groups. The prevalence of a hiatal hernia on manometry was similar between upright and supine refluxers (88% vs 88%). Upright refluxers had shorter hiatal hernias [median (interquartile range) 1.1 (0.65-1.8) vs 1.2 (1-2.3), P < 0.046)]. The median crural pressure, crura-sphincter pressure gradient, and crura-sphincter pressure ratio in upright refluxers was 14.96 (9.5-21.27), 3.28 (1.7-12.2), and 1.33 (0.87-2.8) mm Hg, respectively. These values were significantly higher (P < 0.001) in supine refluxers at 21.43 (16.6-29.9), 10.66 (4.3-19.7), and 2.1 (1.3-4.2) mm Hg, respectively. We conclude that the significantly higher crural pressure in patients with supine reflux acts as a mechanical ring and as a physiologic protector against the unfolding of the sphincter in the postprandial and upright periods. Higher crura-sphincter pressure gradient and larger-size hiatal hernias in patients with supine reflux results in pressurization of the hernia sac and subsequent reflux when these patients are in a supine position.

Esophagus↗

Laparoscopic ultrasonic epithelial ablation of the lower esophagus after nissen fundoplication in a porcine model: assessment of tissue damage and healing process.

A substantial population of patients with Barrett's esophagus has undergone antireflux surgery but still requires annual surveillance endoscopy. These patients would benefit from a definitive ablation of the Barrett's mucosa, which would remove the malignant potential of this disease. This study evaluates the efficacy of applying ultrasonic energy to remove the epithelium of the lower esophagus in a porcine model with prior Nissen fundoplication. Four Yakutan minipigs underwent laparoscopic Nissen fundoplication. After 2 weeks they underwent transgastric Cavitron ultrasonic surgical aspirator (CUSA; Valleylab, Boulder, CO) ablation of the lower esophageal epithelium. Healing of the mucosa was assessed by endoscopy at 2 weeks and pathological examination at 4 weeks after ablation. All pigs underwent successful laparoscopic Nissen fundoplication. Complete lower esophageal epithelial ablation was accomplished through the fundoplication in three animals. One pig developed a bezoar that prohibited ablation. At 2 weeks endoscopy showed patchy squamous epithelial regeneration, which was confirmed histologically. Esophageal specimens at 4 weeks showed complete regeneration of squamous epithelium with a partially healed small ulcer in one animal. No stricture formation was seen. We conclude that the CUSA technique can completely ablate Barrett's mucosa in the setting of a prior antireflux procedure. Healing with squamous mucosal regeneration is rapid and complete.

Animals↗

Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma.

Esophageal adenocarcinoma (EAC) is thought to develop through a multistage process in which Barrett's metaplasia progresses through low- and high-grade dysplasia to invasive cancer. Transcriptional silencing of tumor suppressor genes by promoter CpG island hypermethylation has been observed in many types of human cancer. Analysis of CpG island hypermethylation in EAC has thus far been limited to the CDKN2A (p16) gene. In this study, we extend the methylation analysis of EAC to include three other genes, APC, CDH1 (E-cadherin), and ESR1 (ER, estrogen receptor alpha), in addition to CDKN2A. Molecular analysis can provide insight into the complex relationships between tissues with different histologies in Barrett's esophagus and associated adenocarcinoma. Therefore, we have mapped the spatial distribution of methylation patterns in six esophagectomy cases in detail. Hypermethylation of the four CpG islands was analyzed by the MethyLight technique in 107 biopsies derived from these six patients for a total of 428 methylation analyses. Our results show that normal esophageal squamous epithelium is unmethylated at all four CpG islands. CDH1 is unmethylated in most other tissue types as well. Hypermethylation of ESR1 is seen at high frequency in inflammatory reflux esophagitis and at all subsequent stages, whereas APC and CDKN2A hypermethylation is found in Barrett's metaplasia, dysplasia, and EAC. When it occurs, hypermethylation of APC, CDKN2A, and ESR1 is usually found in a large contiguous field, suggesting either a concerted methylation change associated with metaplasia or a clonal expansion of cells with abnormal hypermethylation.

Adenocarcinoma↗

Is adenocarcinoma following esophagoduodenostomy without carcinogen in the rat reflux-induced?

BACKGROUND: A widely used rat model for reflux-induced esophageal adenocarcinoma in the absence of carcinogens involves induction of duodenoesophageal reflux by performance of esophagoduodenostomy. The aim of this study was to test the hypothesis that acid reflux reduces the incidence of adenocarcinoma in this animal model. METHODS: One hundred ninety 8-week-old male Sprague-Dawley rats were studied. The animals were randomly divided into four groups with a different type of reflux established in each group. Group 1 had an esophagoduodenostomy for duodenogastroesophageal reflux (n = 59), group 2 had an esophagoduodenostomy and a total gastrectomy for duodenoesophageal reflux (n = 54), group 3 had an esophagoduodenostomy and a total gastrectomy with acid supplementation with acidified water to control for the effect of the gastrectomy (n = 50), and group 4 had a total gastrectomy with Roux-en-Y reconstruction to eliminate all reflux (n = 25). One hundred eighty-eight surviving animals were sacrificed at 36 weeks of age and the resected esophagi were examined. RESULTS: All animals except the no reflux control group had severe reflux esophagitis. The frequency of tumor development was similar in all study groups. All of the tumors were well-differentiated adenocarcinomas that were located on the external surface of the bowel either at or immediately distal to the esophagoenteric anastomosis. The tumors appeared to arise from the submucosa and did not involve the overlying mucosa. There was no definite evidence of columnar lining of the esophagus but an admixture of squamous and columnar epithelium was found microscopically in all groups. This finding was unrelated to the presence and composition of reflux. CONCLUSIONS: Adenocarcinomas in this animal model are not reflux-induced and do not arise from the mucosa. Despite previous reports to the contrary, we suggest that this model may not be valid for the study of reflux-induced esophageal adenocarcinoma.

Adenocarcinoma, Mucinous↗

Determinants of intestinal metaplasia within the columnar-lined esophagus.

HYPOTHESIS: The clinical and physiological features of patients with short segments of columnar-lined esophagus (CLE) with and without intestinal metaplasia (IM) are distinct. DESIGN: Retrospective case series. SETTING: University tertiary referral center. PATIENTS: Sixty-five consecutive patients with a 2-cm or shorter length of endoscopically visible CLE. INTERVENTIONS: The type of CLE and the presence of Helicobacter pylori were determined by histopathologic examination of esophageal and gastric antrum biopsy specimens. All patients underwent esophageal manometry and simultaneous 24-hour pH and bilirubin monitoring. MAIN OUTCOME MEASURES: Clinical and physiological data were compared in patients with and without IM. RESULTS: Thirty-six patients had IM and 29 had cardiac-type mucosa without IM in biopsy specimens from the CLE. There was no significant difference in age or sex distribution, but the duration of symptoms was significantly longer in patients with IM (10 vs 5 years; P = .03). Abnormal esophageal acid exposure was found in 30 (83%) of 36 patients with IM and 23 (79%) of 29 patients without IM. The prevalence of abnormal bilirubin exposure was significantly higher in patients with IM (75% [27/36]) than in those without IM (41% [12/29]; P = .01). There was no significant difference in the prevalence of H pylori infection between the 2 groups (8% vs 10%; P >.99). CONCLUSIONS: Patients with short segments of CLE and IM have similar esophageal acid exposure but significantly higher frequency of abnormal bilirubin exposure and longer median duration of reflux symptoms than patients without IM. Therefore, CLE, regardless of histological type, is a manifestation of gastroesophageal reflux disease. The presence of duodenoesophageal reflux and the duration of reflux seem to be important in the pathogenesis of IM.

Barrett Esophagus↗

Laparoscopic repair of large type III hiatal hernia: objective followup reveals high recurrence rate.

BACKGROUND: Recent studies based on symptomatic outcomes analyses have shown that laparoscopic repair of large type III hiatal hernias is safe, successful, and equivalent to open repair. These outcomes analyses were based on a relatively short followup period and lack objective confirmation that the hernia has not recurred. The aim of this study was to compare the outcomes of laparoscopic and open repair of large type III hiatal hernia using both symptomatic evaluation and barium study to assess the integrity of the repair. STUDY DESIGN: Fifty-four patients underwent repair of a large type III hiatal hernia between 1985 and 1998. The surgical approach was laparotomy in 13, thoracotomy in 14, and laparoscopy in 27. An antireflux procedure was included in all patients. Symptomatic outcomes were assessed using a structured questionnaire at a median of 24 months and was complete in 51 of 54 patients (94%). A single radiologist, without knowledge of the operative procedure, assessed the integrity of the repair using video esophagram. Videos were performed at a median of 27 months (35 months open and 17 laparoscopic) and were completed in 41 of 54 patients (75%). RESULTS: Symptomatic outcomes were similar in both groups with excellent or good outcomes in 76% of the patients after laparoscopic repair and 88% after an open repair. Reherniation was present in 12 patients and was asymptomatic in 7. A recurrent hernia was present in 12 of the 41 patients (29%) who returned for a followup video esophagram. Forty-two percent (9 of 21) of the laparoscopic group had a recurrent hernia compared with 15% (3 of 20) of the open group (p < 0.001 log-rank value on recurrence-free followup). CONCLUSIONS: Laparoscopic repair of type III hiatal hernias is associated with a disturbingly high (42%) prevalence of recurrent hernia. More than half such recurrences have few, if any, symptoms.

Adult↗

Evaluation of the intestinal microflora in the rat model for esophageal adenocarcinoma.

Surgically induced duodenal reflux results in cancer development in the rat esophagus. One proposed mechanism of carcinogenesis relies on the production of carcinogens in the presence of bacterial overgrowth. Against this background, intestinal microflora in the rat jejunum was analyzed before and after reflux-inducing surgery. Total gastrectomy and esophagojejunostomy were performed on Sprague-Dawley rats to produce esophageal reflux of duodenal juice (n = 12). Three days before surgery they were randomized into three groups: animals which received tap water; animals which received acidified water at pH 1.8; and animals subjected to oral decontamination with triple antibiotics. During surgery and at autopsy after 2 weeks, intestinal juice was aspirated and analyzed immediately for bacterial content. The physiologic microflora of the rat jejunum contained Lactobacillus spp. and Bacteroides spp., both of which were resistant to the antibiotic regimen. Bacterial overgrowth with fecal bacteria was found following surgery. Acidified water did not alter the intestinal microflora. Triple antibiotics eliminated Escherichia coli and Proteus spp. and reduced the concentration of Enterococcus spp. Bacterial overgrowth by bacteria of the fecal flora occurs in the rat model of esophageal adenocarcinoma with the potential to catalyze the production of carcinogens.

Adenocarcinoma↗

Gastroesophageal reflux disease in asthma: effects of medical and surgical antireflux therapy on asthma control.

OBJECTIVE: To critique the English-language reports describing the effects of medical and surgical antireflux therapy on respiratory symptoms and function in patients with asthma. METHODS: The Medline computerized database (1959-1999) was searched, and all publications relating to both asthma and gastroesophageal reflux disease were retrieved. RESULTS: Seven of nine trials of histamine-receptor antagonists showed a treatment-related improvement in asthma symptoms, with half of the patients benefiting. Only one study identified a beneficial effect on objective measures of pulmonary function. Three of six trials of proton pump inhibitors documented improvement in asthma symptoms with treatment; benefit was seen in 25% of patients. Half of the studies reported improvement in pulmonary function, but the effect occurred in fewer than 15% of patients. In the one study that used optimal antisecretory therapy, asthma symptoms were improved in 67% of patients and pulmonary function was improved in 20%. Combined data from 5 pediatric and 14 adult studies of anti-reflux surgery indicated that almost 90% of children and 70% of adults had improvement in respiratory symptoms, with approximately one third experiencing improvements in objective measures of pulmonary function. CONCLUSIONS: Fundoplication has been consistently shown to ameliorate reflux-induced asthma; results are superior to the published results of antisecretory therapy. Optimal medical therapy may offer similar results, but large studies providing support for this assertion are lacking.

Adult↗

Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia.

OBJECTIVE: To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. SUMMARY BACKGROUND DATA: The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. METHODS: DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. RESULTS: p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar. CONCLUSIONS: Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.

Adenocarcinoma↗

Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy.

OBJECTIVE: To outline current concepts regarding etiology, diagnosis, and treatment of intestinal metaplasia of the esophagus and cardia. SUMMARY BACKGROUND DATA: Previously, endoscopic visualization of columnar mucosa extending a minimum of 3 cm into the esophagus was sufficient for the diagnosis of Barrett's esophagus, but subsequently the importance of intestinal metaplasia and the premalignant nature of Barrett's have been recognized. It is now apparent that shorter lengths of intestinal metaplasia are common, and share many features of traditional 3-cm Barrett's esophagus. METHODS: Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review of the literature published between 1950 and 1999. RESULTS: Cardiac mucosa is the precursor of intestinal metaplasia of the esophagus. Both develop as a consequence of gastroesophageal reflux. Intestinal metaplasia, even a short length, is premalignant, and the presence of dysplasia indicates progression on the pathway to adenocarcinoma. Antireflux surgery, as opposed to medical therapy, may induce regression or halt progression of intestinal metaplasia. The presence of high-grade dysplasia is frequently associated with an unrecognized focus of adenocarcinoma. Vagal-sparing esophagectomy removes the diseased esophagus and is curative in patients with high-grade dysplasia. Invasion beyond the mucosa is associated with a high likelihood of lymph node metastases and requires lymphadenectomy. CONCLUSIONS: Despite improved understanding of this disease, controversy about the definition and best treatment of Barrett's esophagus continues, but new molecular insights, coupled with careful patient follow-up, should further enhance knowledge of this disease.

Barrett Esophagus↗

Short esophagus: analysis of predictors and clinical implications.

HYPOTHESIS: Preoperative assessment can identify the predictors of esophageal shortening in patients with gastroesophageal reflux disease. DESIGN AND SETTING: Patient comparison study in a university-based tertiary care center. PATIENTS: A total of 236 patients with gastroesophageal reflux disease underwent primary antireflux procedures. Sixty-five patients were suspected of having a short esophagus and underwent a transthoracic approach. In 37 patients, a lengthening procedure was necessary to avoid tension on the repair. The remaining 28 patients were thought-after complete esophageal mobilization-to have sufficient length for a repair without needing a gastroplasty. An abdominal approach (laparoscopic Nissen fundoplication) was performed on 171 patients judged to have normal esophageal length. MAIN OUTCOME MEASURES: Univariate and multivariate analyses of preoperative variables were performed to identify predictors of a short esophagus. RESULTS: On univariate analysis, manometric esophageal length below the fifth percentile of normal was associated with esophageal shortening. On multivariate analysis, only the presence of an esophageal stricture predicted the need for a Collis gastroplasty (odds ratio, 7.5). The presence of Barrett's esophagus of 3 cm or greater identified patients in whom the transthoracic esophageal mobilization alone was sufficient (odds ratio, 3.4). CONCLUSIONS: The presence of a stricture was associated with esophageal shortening sufficient to require a gastroplasty. Transthoracic esophageal mobilization alone was usually sufficient to perform a safe repair without tension in patients with a Barrett's esophagus of 3 cm or greater.

Adolescent↗

Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease.

HYPOTHESIS: Helicobacter pylori is not associated with gastroesophageal reflux disease and its complications, including adenocarcinoma of the esophagus and the gastroesophageal junction (GEJ). DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Two hundred twenty-nine patients with symptoms suggestive of foregut disease underwent esophageal manometry, 24-hour pH monitoring, and upper gastrointestinal tract endoscopy, with biopsy specimens obtained from the gastric antrum, the GEJ, and the distal esophagus. In these and in an additional 114 patients with adenocarcinoma of the esophagus and the GEJ, the presence of H. pylori was determined by Giemsa stain. The presence of gastroesophageal reflux disease, defined by abnormal esophageal acid exposure, and its manifestations (carditis, erosive esophagitis, intestinal metaplasia limited to the GEJ, Barrett esophagus, and adenocarcinoma of the esophagus and GEJ) were correlated with the presence of H. pylori. RESULTS: Helicobacter pylori was found on the biopsy specimens of the gastric antrum in 14.0% (32/229) of the patients with benign disease. It was not related to the features of gastroesophageal reflux disease, including abnormal esophageal acid exposure, erosive esophagitis, or Barrett esophagus. The presence of inflamed cardiac mucosa at the GEJ or carditis was inversely related to H. pylori infection and strongly associated with increased esophageal acid exposure. There was no association between the presence of intestinal metaplasia and H. pylori infection. Helicobacter pylori was found in 22 (19.3%) of the 114 patients with esophageal adenocarcinoma, which was not different from the prevalence of H. pylori in patients with benign disease. CONCLUSION: Helicobacter pylori plays no role in the pathogenesis of gastroesophageal reflux disease or its complications.

Adolescent↗

The pattern of esophageal acid exposure in gastroesophageal reflux disease influences the severity of the disease.

HYPOTHESIS: There is an independent association between the different patterns of esophageal acid exposure in gastroesophageal reflux disease and the severity of the disease. DESIGN: Case-comparison study. SETTING: Department of surgery at a university hospital. PATIENTS: A group of 401 patients with increased esophageal acid exposure divided into 4 groups according to the pattern of reflux: postprandial (n = 41), upright (n = 74), supine (n = 129), and bipositional (n = 157). MAIN OUTCOME MEASURES: The prevalence of mucosal injury and the status of the lower esophageal sphincter and esophageal motility were assessed in each group. RESULTS: The likelihood of having indicators of the severity of gastroesophageal reflux disease increases progressively from postprandial to upright, supine, and bipositional reflux. CONCLUSIONS: The pattern of esophageal acid exposure in gastroesophageal reflux disease is an objective predictor of the severity of disease and could be used for therapeutic decisions.

Case-Control Studies↗

Endoscopic grading of the gastroesophageal valve in patients with symptoms of gastroesophageal reflux disease (GERD).

BACKGROUND: It has been suggested that endoscopic grading of the gastroesophageal flap valve is a good predictor of the reflux status. METHODS: To test this hypothesis, 268 symptomatic patients underwent endoscopic grading of the gastroesophageal valve using Hill's classification, with grades I through IV. Esophageal acid exposure, lower esophageal sphincter characteristics, and the degree of esophageal mucosal injury were compared among the groups. RESULTS: The prevalence of a mechanically defective sphincter, abnormal esophageal acid exposure, erosive esophagitis, and Barrett's esophagus increased with increasing alteration of the gastroesophageal valve. The presence of a grade IV valve indicated increased esophageal acid exposure in 75% of patients. As a predictor, this is similar to lower esophageal sphincter pressure but not as good as the presence of esophageal mucosal injury. CONCLUSIONS: Endoscopic grading of the gastroesophageal valve provides useful information about the reflux status but is less useful as an indicator of gastroesophageal reflux disease (GERD) than the presence of esophageal mucosal injury.

Adolescent↗