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S Sontag

Publications and source records attributed to S Sontag.

15 recordsLinked to original sources
PubMed2001

Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial.

CONTEXT: Severe gastroesophageal reflux disease (GERD) is a lifelong problem that can be complicated by peptic esophageal stricture and adenocarcinoma of the esophagus. OBJECTIVE: To determine the long-term outcome of medical and surgical therapies for GERD. DESIGN AND SETTING: Follow-up study conducted from October 1997 through October 1999 of a prospective randomized trial of medical and surgical antireflux treatments in patients with complicated GERD. Mean (median) duration of follow-up was 10.6 years (7.3 years) for medical patients and 9.1 years (6.3 years) for surgical patients. PARTICIPANTS: Two hundred thirty-nine (97%) of the original 247 study patients were found (79 were confirmed dead). Among the 160 survivors (157 men and 3 women; mean [SD] age, 67 [12] years), 129 (91 in the medical treatment group and 38 in the surgical treatment group) participated in the follow-up. MAIN OUTCOME MEASURES: Use of antireflux medication, Gastroesophageal Reflux Disease Activity Index (GRACI) scores, grade of esophagitis, frequency of treatment of esophageal stricture, frequency of subsequent antireflux operations, 36-item Short Form health survey (SF-36) scores, satisfaction with antireflux therapy, survival, and incidence of esophageal adenocarcinoma, compared between the medical antireflux therapy group and the fundoplication surgery group. Information on cause of death was obtained from autopsy results, hospital records, and death certificates. RESULTS: Eighty-three (92%) of 90 medical patients and 23 (62%) of 37 surgical patients reported that they used antireflux medications regularly (P<.001). During a 1-week period after discontinuation of medication, mean (SD) GRACI symptom scores were significantly lower in the surgical treatment group (82.6 [17.5] vs 96.7 [21.4] in the medical treatment group; P =.003). However, no significant differences between the groups were found in grade of esophagitis, frequency of treatment of esophageal stricture and subsequent antireflux operations, SF-36 standardized physical and mental component scale scores, and overall satisfaction with antireflux therapy. Survival during a period of 140 months was decreased significantly in the surgical vs the medical treatment group (relative risk of death in the medical group, 1.57; 95% confidence interval, 1.01-2.46; P =.047), largely because of excess deaths from heart disease. Patients with Barrett esophagus at baseline developed esophageal adenocarcinomas at an annual rate of 0.4%, whereas these cancers developed in patients without Barrett esophagus at an annual rate of only 0.07%. There was no significant difference between groups in incidence of esophageal cancer. CONCLUSION: This study suggests that antireflux surgery should not be advised with the expectation that patients with GERD will no longer need to take antisecretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett esophagus.

Adenocarcinoma↗
PubMed1995

Treatment of erosive reflux esophagitis resistant to H2-receptor antagonist therapy. Lansoprazole, a new proton pump inhibitor.

Fifty-four patients with endoscopically documented therapy-resistant erosive reflux esophagitis were treated with lansoprazole, a new proton pump inhibitor, for up to 12 weeks. Prior to entry, all had remained unhealed after treatment with at least two histamine2-receptor antagonists, at therapeutic doses or higher, for at least 12 weeks. Patients were randomized to receive either 30 or 60 mg lansoprazole once daily. Endoscopy was performed and symptoms assessed at weeks 2,4,6,8 and 12. Fifty-nine percent of the 50 evaluable patients were healed (ie, no evidence of erosions) after only two weeks of lansoprazole. Cumulative endoscopic healing rates were 82% and 92% by week 4 and week 8, respectively, and the two doses were equally effective in healing. The 30- and 60-mg doses effected a decrease in the overall symptom score from 5.30 and 4.85 to 2.35 and 1.67, respectively, by the final treatment visit (P = 0.001). No clinically significant adverse events or changes in laboratory parameters were observed, and no patients withdrew prematurely from the study. This study demonstrates that lansoprazole therapy is highly effective in healing erosive reflux esophagitis resistant to therapy with histamine H2-receptor antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Mucosal reactive oxygen species production in oesophagitis and Barrett's oesophagus.

Reactive oxygen species (ROS) produced by inflammatory cells can contribute to tissue destruction. ROS have been implicated in various gastrointestinal abnormalities, including the acid related peptic diseases. Although the development of oesophagitis and Barrett's columnar epithelium is associated with prolonged reflux of gastric acid, the exact mechanism by which tissue damage occurs is not known. To discover if ROS are involved in damage to the oesophageal mucosa, this study measured in vitro the mucosal ROS concentrations of biopsied mucosal samples taken from patients with reflux oesophagitis using luminol enhanced chemiluminescence (LECL). Mucosal biopsy specimens were taken from 83 patients: 19 with normal oesophageal mucosa (group I); 20 with macroscopic oesophagitis (group II); 20 with biopsy confirmed Barrett's epithelium without macroscopic oesophagitis (group III); and 24 with Barrett's epithelium with macroscopic oesophagitis (group IV). The mucosa from patients exhibited significantly higher LECL values than the mucosa from controls. But, there were no significant differences between groups II, III, and IV. Addition of the myeloperoxidase inhibitor, azide, or the hydrogen peroxide scavenger, catalase, to the tissue suspension caused a decrease in LECL values of 32% and 45%, respectively, suggesting that neutrophils--although important--are not the only source of mucosal LECL. These data are consistent with the proposal that ROS play an important part in the tissue injury associated with oesophagitis and Barrett's columnar epithelium.

Aged↗
PubMed1993

Increased levels of luminol-enhanced chemiluminescence by rectal mucosa of patients with colonic neoplasia: a possible marker for colonic neoplasia.

Increased colonic cell proliferation (CCP) has been reported in patients with colonic neoplasia. Previous studies in rats suggest that increased CCP is closely related to increased reactive oxygen metabolite (ROM) production. We hypothesized that, in humans, ROM production is also involved in increased CCP. Using a chemiluminescence probe, we estimated the levels of ROMs in the rectal mucosa of 37 patients who previously had colonic neoplasia (14 with cancer and 23 with polyps) and 20 control subjects who had normal colonoscopic examination and no history of colonic neoplasia. Normal-appearing rectal mucosa of patients with colonic neoplasia contained significantly higher levels of luminol-enhanced chemiluminescence (LECL) than rectal mucosa of control subjects (p < 0.01). There was no difference in LECL levels between patients with polyps and patients with cancer. Four of 20 controls and 31 of 37 patients had LECL levels 1,000 cpm/mg protein (positive and negative predictive values of 89% and 73%, respectively). Addition of indomethacin, a specific cyclooxygenase inhibitor, to the tissue suspension significantly decreased LECL levels. These preliminary data suggest that 1) ROMs may be involved in both the rate of CCP and the process of malignant cellular transformation, 2) oxidation of arachidonic acid via the cyclooxygenase pathway significantly contributes to the production of ROMs in rectal mucosa, and 3) measurement of the levels of LECL produced by the rectal mucosa may be a sensitive marker to screen for colonic neoplasia.

Adult↗
PubMed1991

Gastric emptying in patients with severe reflux esophagitis.

The pathogenesis of gastroesophageal reflux (GER) is not fully understood. There have been reports that delayed gastric emptying is a contributing factor in some patients. To determine whether delayed gastric emptying plays a role in the genesis of GER, we correlated gastric-emptying measures obtained by scintigraphic techniques with the degree of acid reflux assessed by esophageal pH monitoring. Ten patients, all of whom had evidence of esophageal mucosal disease and severe acid reflux, were studied. Four of the 10 patients with reflux had prolongation in the lag phase of gastric solid emptying, and one of the four showed prolonged gastric-emptying t1/2. There was no significant difference, however, in the mean gastric-emptying t1/2 between a control group and the patient group. Furthermore, there was no correlation between gastric-emptying measures and degree of acid reflux. We conclude that in this group of 10 patients with severe GER, delayed gastric emptying does not play an important role in the development of gastroesophageal reflux.

Adult↗
PubMed1988

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗
PubMed1987

Effect of smoking in a controlled study of ranitidine treatment in gastroesophageal reflux disease.

Smoking has been shown to be a factor in acid peptic disease. A recent U.S. multicenter trial investigating use of ranitidine in the treatment of gastroesophageal reflux disease provided an opportunity to compare smokers and nonsmokers with regard to demographic features, manifestations of disease, and symptomatic response to treatment. A comparison of characteristics of smokers and nonsmokers revealed similar pretrial clinical findings. No significant differences between groups were found with regard to previous complications or recent symptoms of gastroesophageal reflux disease. There were also no significant differences in the way smokers and nonsmokers responded to treatment. Subjects on ranitidine, regardless of their smoking status, showed significantly greater improvement in heartburn symptoms and consumed less antacid than subjects who received placebo. Results of these analyses indicate that smoking as an independent variable was not related to symptomatic response or esophageal healing and that ranitidine was similarly effective in decreasing heartburn symptoms in smokers and nonsmokers.

Adult↗
PubMed1987

Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial.

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.

Adult↗
PubMed1987

Is gastroesophageal reflux a factor in some asthmatics?

We performed antireflux surgery on 13 adults with both gastroesophageal reflux (GER) and asthma. The duration of asthma ranged from 7 months to 43 yr. Twelve patients had chronic heartburn, 10 had nocturnal cough and wheezing, eight had chest pain, and one was asymptomatic for GER. GER was determined by a combination of esophagoscopy with biopsy, manometry, and esophageal pH testing. Postoperative follow-up ranged from 13 months to 5 yr. Six patients were completely free of all wheezing episodes, six still had wheezing but the frequency and severity had markedly decreased, and one remained unchanged. Of 11 patients who required chronic bronchodilator therapy, four were able to completely stop and six decreased the dose by more than half; one required the same amount of therapy. Of the seven corticosteroid-dependent patients, two were weaned completely, three were being tapered, one remained unchanged, and one required a smaller dose for nasal polyps although he was free of wheezing and had stopped bronchodilators. Three patients, all of whom dramatically improved after surgery, died during their follow-up course: one died suddenly 8 months postoperatively during a walk after dinner from apparent status asthmaticus; one died 9 months postoperatively of refractory congestive heart failure; and one died 30 months postoperatively of metastatic adenocarcinoma of unknown source. We conclude that surgical correction of GER in selected adults with both asthma and GER may significantly decrease or eliminate pulmonary symptoms and the need for asthmatic medications.

Adult↗
PubMed1985

Postsurgical chylous ascites in sarcoidosis with portal hypertension.

A patient with extensive thromboses of portal and mesenteric veins and sarcoid of the liver developed recurrent pulmonary emboli, which necessitated the insertion of an umbrella into the inferior vena cava. Chylous ascites appeared shortly thereafter; the ascitic fluid fat content was strikingly reduced after reduction of dietary long chain triglycerides, but the ascitic fluid volume was reduced only after insertion of a peritoneovenous shunt (LeVeen). The shunt was found to be nonfunctioning 4 months later, but ascites did not recur. Seven years later, while eating a normal diet and still having a nonfunctioning shunt, he remains free of ascites. We postulate that iatrogenic obstruction of the inferior vena cava in the presence of mesenteric and portal vein thromboses, as well as obstruction of mesenteric lymphatics by sarcoid lymphadenopathy, led to the formation of chylous ascites and that establishment of adequate mesenteric and portal venous and/or lymphatic collateral circulation was responsible for his sustained improvement.

Biopsy↗
PubMed1984

Cimetidine, cigarette smoking, and recurrence of duodenal ulcer.

Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.

Cimetidine↗
PubMedDate not supplied

Barrett's esophagus. The cytology of dysplasia in comparison to benign and malignant lesions.

Barrett's esophagus (BE) is the replacement of esophageal squamous epithelium by columnar-lined mucosa and carries an increased risk of carcinoma. Endoscopic surveillance has been suggested, but esophageal brush cytology (BC) has not been widely utilized. Cytologic descriptions of BE, especially dysplasias, are sparse. We studied matched cytologic and histologic materials from 26 patients with BE and 4 patients with concurrent BE and adenocarcinoma. In six patients without dysplasia on biopsy, BE was recognized on BC by the presence of goblet cells within clusters of uniform columnar cells with vesicular nuclei. Dysplasia in 18 BC samples revealed small clusters of haphazardly oriented, mildly pleomorphic cells. Their larger nuclei had thickened membranes, evenly dispersed chromatin and occasional multiple nucleoli. The cytologic differentiation of histologically graded low- and high-grade dysplasia was difficult. The carcinoma cases displayed numerous isolated cells exhibiting flagrant malignant features. We conclude that BE lesions are cytologically distinctive and suggest that BC may play a role in surveillance.

Adenocarcinoma↗