Search PubMed⌕ Search

Biomedical subjects

T R Demeester

Publications and source records attributed to T R Demeester.

At least 19 recordsLinked to original sources
PubMed2004

'Efficacy' of esophageal peristalsis: a manometric parameter to quantify esophageal body dysfunction.

Esophageal motor abnormalities are currently categorized into separate entities based on standard manometry. The clinical significance of these categories is controversial. We evaluated whether ambulatory 24-h esophageal motility monitoring improves the assessment of patients thought to have a primary esophageal motor disorder. Standard and ambulatory 24-h esophageal motility records of 30 healthy volunteers and 136 symptomatic patients were compared. Regression analysis was used to identify parameters that relate to the presence of nonobstructive dysphagia. Prolonged ambulatory esophageal monitoring showed a marked circadian variation in the esophageal motor pattern and significant discrepancies to the findings on standard manometry in 47% of the 136 patients. Discrepancies were particularly frequent in patients categorized on standard manometry as having a 'nutcracker esophagus' or a nonspecific motor disorder. Of all data obtained, the prevalence of 'effective contractions', i.e. peristaltic contractions with an amplitude > 30 mmHg, during meal periods provided the best correlation with the presence of nonobstructive dysphagia. Of the 78 patients with nonobstructive dysphagia 71 (92%) had less than 50% of 'effective contractions' during meals. In five patients who had frequent simultaneous wave forms and less than 70%'effective contractions' during meals a long myotomy markedly reduced the severity of dysphagia. The 'efficacy' of esophageal contractions during meals best relates to patients' symptoms and allows expression of esophageal body dysfunction on a linear scale. This obviates the need for the current categories of esophageal motor disorders, permits an objective assessment of medical therapy and may improve the identification of patients that benefit from a surgical myotomy of the esophageal body.

Adolescent↗
PubMed2004

Esophageal adenocarcinoma in patients < or = 50 years old: delayed diagnosis and advanced disease at presentation.

During the past decade, we encountered an increasing number of young patients with esophageal adenocarcinoma. It is not clear whether young patients have more aggressive course and worse prognosis. Our aim was to compare clinicopathological characteristics/treatment results of patients with esophageal adenocarcinoma who were < or = 50 and > 50 years of age. We studied 263 consecutive patients with resectable esophageal adenocarcinoma: 32 (12.1%) were < or = 50 years old. Dysphagia was present in 69 per cent of patients < or = 50 years old and in 48 per cent of older patients (P = 0.019). The median duration of dysphagia was 3.5 months in younger patients compared to 2 months in patients > 50 years (P < 0.0001). Seven of 22 (31.8%) young and three of 108 (2.8%) older patients with dysphagia reported dysphagia for > or = 6 months (P < 0.0001). Fifty per cent of younger patients were stage III/IV and > 70 per cent were node positive (P = 0.04 and P = 0.02 vs patients > 50 years, respectively). Five-year survival was 32.6 per cent for < or = 50 years and 45.5 per cent for > 50 years. More than 10 per cent of esophageal adenocarcinoma patients undergoing surgery are now < or = 50 years of age. They usually present with dysphagia, are symptomatic for a longer time before diagnosis, and have more advanced disease compared to older patients. With appropriate aggressive treatment, survival is similar. Liberal use of endoscopy and aggressive diagnostic approach are paramount in young patients with dysphagia/symptoms of gastroesophageal reflux disease (GERD).

Adenocarcinoma↗
PubMed2001

Retinoic acid receptor-alpha messenger RNA expression is increased and retinoic acid receptor-gamma expression is decreased in Barrett's intestinal metaplasia, dysplasia, adenocarcinoma sequence.

BACKGROUND: Expression levels of the retinoic acid receptors (RAR-alpha, RAR-beta, and RAR-gamma) are significantly different in neoplastic tissues compared with non-neoplastic tissues for some tumors. This study investigated whether retinoic acid receptor messenger RNA (mRNA) expression levels are altered in Barrett's esophagus and Barrett's adenocarcinoma tissues. METHODS: Relative mRNA expression levels of the RARs were quantified by using the ABI 7700 Sequence Detector (Taqman) system in Barrett's intestinal metaplasia (n = 15), dysplasia (n = 6), adenocarcinoma (n = 17), and matching normal esophagus tissues (n = 36). RESULTS: RAR-alpha expression was significantly increased, and RAR-gamma expression was significantly decreased, at higher stages in the Barrett's sequence. There was almost complete loss of RAR-gamma expression (relative expression level < or = 1) in a majority (70%) of the dysplasia and adenocarcinoma tissues. There were significant differences in RAR-alpha and RAR-gamma expression in histopathologically normal tissues in patients with cancer versus patients without cancer. RAR-beta expression levels were significantly elevated in adenocarcinoma versus normal esophagus tissues. The RAR expression profile was similar for cancers arising within the esophagus and for cancers arising at the gastroesophageal junction. CONCLUSIONS: RAR mRNA expression levels are significantly different in Barrett's tissues compared with normal esophagus tissues, and these levels are significantly different in Barrett's dysplasia and adenocarcinoma tissues compared with nondysplastic tissues. These results suggest that RAR mRNA levels may be useful biomarkers for this disease and that gastroesophageal junction adenocarcinomas are genetically similar to esophageal adenocarcinomas. These results also suggest that a cancer field is present in the esophagus in patients with cancer and that genetic alterations can precede histopathologic alterations in this disease.

Adenocarcinoma↗
PubMed2000

Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.

BACKGROUND: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. METHODS: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P: value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P =.016). CONCLUSION: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

Adenocarcinoma↗
PubMed2000

Definition of histopathologic changes in gastroesophageal reflux disease.

A series of 71 patients with multiple measured biopsies of the gastroesophageal junctional region permitting assessment of the presence and length of different glandular epithelial types is presented. All but nine of 53 patients in whom a 24-hour pH study was performed had abnormal reflux, suggesting that endoscopic recognition of an abnormal columnar mucosa at the gastroesophageal junction sufficient to precipitate multiple-level biopsies indicates a high probability of abnormal reflux. All patients had cardiac mucosa (CM) or oxyntocardiac mucosa (OCM). CM was present in 68 of 71 patients. The prevalence of intestinal metaplasia increased with increasing CM+OCM length, and was present in all 22 patients with a CM+OCM length >2 cm and in 20 of 49 patients with a CM+OCM length <2 cm. Patients with a CM+OCM length >2 cm had a markedly higher acid exposure than patients with a CM+OCM length <2 cm. The findings suggest that the presence of CM and OCM in the junctional region are predictive of abnormal acid exposure, and that increasing OCM+CM length correlates strongly with the amount of acid exposure. The histologic finding of CM and OCM represents a sensitive histologic criterion for gastroesophageal reflux rather than normal epithelia. These diagnostic criteria represent the first useful histologic definitions for assessing the presence and severity of reflux.

Gastric Mucosa↗
PubMed1999

Abnormal esophageal body function: radiographic-manometric correlation.

Stationary manometry is the gold standard for the evaluation of patients with suspected esophageal motility disorders. Comparison of videoesophagram in the evaluation of esophageal motility disorders with stationary motility has not been objectively studied. Two hundred two patients with foregut symptoms underwent stationary motility and videoesophagram. Radiographic assessment of esophageal motility was done by video recording of five 10-cc swallows of barium. Abnormal esophageal body function was defined by stasis of barium in the middle third of the esophagus on at least four swallows or stasis on at least three swallows in the distal third. Stationary manometry was performed using a five-channel water perfused system. Contraction amplitudes <25 mm Hg in any of the last two channels or the presence of simultaneous or interrupted waves in 10 per cent or more were considered to be abnormal. Sixty-two patients had abnormal manometry. Thirty-four patients also demonstrated abnormal videoesophagrams for an overall sensitivity of 55 per cent. The positive predictive value was 53 per cent; specificity was 79 per cent; and negative predictive value was 80 per cent. Sensitivity was greatest in patients with achalasia (94%) and scleroderma (100%) and in patients presenting with dysphagia (89%). Sensitivity was poor for nonspecific esophageal motility disorders. A videoesophagram is relatively insensitive in detecting motility disorders. It seems most useful in the detection of patients with esophageal dysfunction, for which surgical treatment is beneficial, and in those patients presenting with dysphagia.

Adolescent↗
PubMed1998

Proceedings from an international conference on ablation therapy for Barrett's mucosa. Brittany, France, 31 August-2 September 1997.

The increasing incidence of adenocarcinoma of the lower esophagus and cardia arising in Barrett's metaplastic epithelium continues to be of great concern because medical and surgical efforts to reverse the process have been disappointing. A potential answer to the problem is removal of the metaplastic epithelium. Modern technology has introduced physical and chemical modalities which facilitate ablation of the neo-epithelium endoscopically. These techniques have been used in several centers, and preliminary results are encouraging. This report summarizes the proceedings of an international symposium on ablative therapy held in Brittany, France in August 1997. Twenty-eight speakers contributed to the talks on the pathology, pathogenesis, current therapy experimental studies and clinical experience of ablation of Barrett's esophagus.

Adenocarcinoma↗
PubMed1993

Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome.

Small numbers of intraepithelial esophageal eosinophils (IEE) may be seen in 50% of patients with gastroesophageal reflux disease and occasionally in normal volunteers. High concentrations of IEE are rarely seen in either setting. During a two-year period we identified 12 adult patients with very dense eosinophil infiltrates in esophageal biopsies (defined as > 20 IEE/high-power field). Dysphagia was the presenting complaint in each, but no evidence of anatomical obstruction could be found. Endoscopic esophagitis was absent, but biopsy showed marked squamous hyperplasia and many IEE. Eleven patients had normal esophageal acid exposure on 24-hr pH monitoring. Esophageal manometry showed a nonspecific motility disturbance in 10 patients. For comparison, 90 patients with excess esophageal acid exposure on 24-hr pH monitoring were studied. Thirteen (14%) had motility disturbance, and 21 (23%) had dysphagia. Esophageal biopsies were devoid of IEE in 47 patients; none of the 43 with IEE had infiltrates as dense as those seen in the 12 study patients. The presence of high concentrations of IEE in esophageal biopsies from patients with dysphagia, normal endoscopy, and normal 24-hr esophageal pH monitoring represents a distinctive clinicopathologic syndrome not previously described.

Adult↗
PubMed1990

Drug-induced esophageal injury. Histopathological study in a rabbit model.

The purpose of this animal study was to investigate the histopathologic consequences of esophageal exposure to a variety of medications known to be injurious to the human esophagus. Twenty-four New Zealand white rabbits were utilized. Tablets or control plastic beads were secured to a silk suture thread and positioned in the rabbit esophagus through a proximal esophagostomy and a gastrostomy. Test medications were allowed to dissolve passively on the surface of the esophageal mucosa in the anesthetized rabbits. After 1 hr of drug exposure, the rabbits were killed and the esophagus removed and examined. No gross abnormalities were detected with the exception of a mild degree of erythema at some of the exposure sites. All medications and control beads produced microscopic mucosal changes when compared to suture controls. The beads and test medications caused thinning of the epithelium and increased subepithelial edema (P less than 0.05). Two changes, however, were unique to animals exposed to test medications: fraying and/or splitting of the epithelium and the presence of balloon cells (P less than 0.05). Balloon cells represent damaged squamous epithelial cells recognizable by their distended, globoid shape. The prevalence of balloon cells ranged from 22% to 89% of sites exposed to drug and was most commonly associated with potassium. Of all drugs reported to cause injury to the human esophagus, potassium chloride has been reported to produce the most severe lesions, including esophageal stricture and perforation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Metastatic non-small cell bronchogenic carcinoma: a randomized trial of sequential vs combination chemotherapy.

In order to determine whether combination chemotherapy offered any advantage over single-agent therapy in cases of metastatic non-small cell bronchogenic carcinoma, we performed a randomized study in 56 patients comparing combination chemotherapy (cyclophosphamide, doxorubicin, methotrexate, procarbazine, leucovorin--CAMP-L) with a regimen in which the same drugs were given sequentially (methotrexate/leucovorin followed by cyclophosphamide/doxorubicin at progression). Of the patients receiving the combination, 52% (14 of 27) had either a partial response or stable disease, compared to 17% (5 of 29) in the sequential group. Of the patients with adenocarcinoma, those in the combination group had a significantly longer survival than those treated in the sequential group (medians, 10.0 vs 2.8 months; P less than 0.01); such a difference could not be demonstrated for patients with squamous carcinoma. Patients who achieved a partial response had a median survival of 15.3 months; those with stable disease survived a median of 10.0 months; and those with no response survived a median of 2.5 months (P less than 0.0001). Four patients died from chemotherapy-related complications: three from methotrexate toxicity and resultant infection and one from pneumonia associated with neutropenia. We conclude that the short survival of non-responding patients and the survival benefit accompanying response or stabilization make early aggressive combination therapy useful for patients with metastatic non-small cell lung cancer.

Adenocarcinoma↗
PubMed1978

Esophageal epithelial response to gastroesophageal reflux. A quantitative study.

Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux.

Esophagus↗
PubMed1976

Patterns of gastroesophageal reflux in health and disease.

Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.

Deglutition Disorders↗