Drug-induced esophageal damage: diseases of medical progress.
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Biomedical subjects
Publications and source records attributed to H W Boyce.
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Since 1992 there have been reports of proton pump inhibitors being associated with fundic gland-type gastric polyps. Endoscopic and histologic characteristics and natural history of these polyps have not been clearly defined. We performed a retrospective study of patients on long-term treatment with proton pump inhibitors who developed gastric polyps. Gastric polyps developed in 17 (10 males and 7 females, 7.3%) of the 231 patients who underwent 2 or more upper endoscopies for complicated gastroesophageal reflux disease and who were receiving long-term treatment with proton pump inhibitors. The mean interval of proton pump inhibitor use after which an endoscopy revealed gastric polyps was 32.5 months. In 1 patient, discontinuation of treatment resulted in disappearance of the polyps within 3 months. The polyps recurred 4 months after the treatment was restarted. Endoscopy established that typical polyps were generally small (<1 cm), sessile, multiple, and whitish pink with a mottled partially translucent surface. The polyps were most often present in the proximal/midgastric body. Of the 15 polyps removed endoscopically, 9 were of the fundic gland type, 4 were of the hyperplastic type, and 2 were of the inflammatory type. Eight of 9 polyps with typical endoscopic appearance were of the fundic gland type. None of the polyps contained dysplasia or carcinoma. Long-term use of proton pump inhibitors may be associated with the presence of small gastric fundic gland polyps and hyperplastic polyps. A prospective study is required to establish their incidence, natural history, and clinical significance.
Tissue staining during endoscopy (chromoendoscopy) is a technique used to study the fine details of the mucosa throughout the gastrointestinal tract. Unfortunately, its applications and results are not known by many gastrointestinal or surgical endoscopists. Each stain has a few specific clinical applications. The mechanism of action of the stains should be fully understood before their use. Ideally, the clinician should use chromoendoscopy and the variety of stains either to confirm a clinical suspicion or to provide new information that could aid management in a specific setting. Endoscopic tattooing is a different technique where a specific site in the gastrointestinal tract is labeled by an intramural injection of a carbon ink suspension solution for future surgical or endoscopic identification.
BACKGROUND: Endosonography (EUS) is a valuable technique for diagnosing gastrointestinal stromal cell tumors. However, EUS features that are predictive of malignancy in these tumors have not been defined. METHODS: Videotapes and photographs of EUS examinations performed prior to surgical resection of 35 stromal cell tumors (9 malignant) were blindly reviewed by a single examiner. EUS features associated with malignancy were determined. Interobserver agreement in interpreting these features was then measured among a panel of five expert endosonographers who judged EUS videotapes of 35 resected stromal cell tumors (10 malignant). RESULTS: Stepwise logistic regression analysis demonstrated that tumor size (diameter > 4 cm), irregular extraluminal border, echogenic foci, and cystic spaces were independently associated with malignancy in stromal cell tumors (p < 0.05). Interobserver agreement for irregular extraluminal border, echogenic foci, and cystic spaces, as measured by mean kappa statistic, was 0.43, 0.39, and 0.28, respectively. For the five experts, the sensitivity for detecting malignancy ranged between 80% to 100% when at least two of the three features were judged to be present. The likelihood of finding malignancy ranged between 0% to 11% for the experts when all three features were judged absent. CONCLUSIONS: Tumor size and certain EUS features are useful for predicting malignancy in stromal cell tumors. Absence of these features indicates benign disease. Agreement among experts in interpreting these EUS features is fair to moderate.
Medical therapy for reflux esophagitis is designed to provide symptom relief and esophageal healing, and to prevent complications. Life-style modifications serve as an adjunct to drug therapy. Sucralfate, prokinetic agents, and H2-receptor antagonists promote symptom relief and esophageal healing in mild esophagitis, but are less effective in the treatment of moderate to severe esophagitis. For patients with mild to severe (erosive) esophagitis, rapid symptom relief and esophageal healing have been achieved with proton pump inhibitors such as omeprazole and lansoprazole.
BACKGROUND: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. METHODS: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. RESULTS: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/- SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). CONCLUSIONS: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed.
BACKGROUND: Despite increased clinical use of endoscopic ultrasound (EUS), there are little data regarding complications of EUS or its impact on patient management. METHODS: A prospective multicenter study was completed to evaluate clinical outcomes of EUS. Before each EUS examination the endosonographer recorded further theoretical patient management plans as if EUS was unavailable. After the EUS, endosonographers recorded actual management plans based on EUS results. The actual management plan after EUS was compared to the theoretical management before EUS. Complications were assessed in short-term follow-up. RESULTS: Four hundred twenty-eight subjects were enrolled. Of subjects able to be evaluated, EUS changed the treatment plan in 74%. Management changes of major importance occurred in 120 patients (31% of subjects able to be evaluated) and included decisions regarding surgery (62 patients), decisions regarding nonsurgical invasive management (36 patients), and decisions regarding further follow-up (22 patients). When there was a change in management, the change was to less costly, risky, or invasive management in 55%, to more costly/risky/invasive in 37%, and to equally costly/risky/invasive in 8%. Short-term follow-up was completed in 81% of subjects, with six complications identified (1.7%). Three complications were mild, two were moderate, one severe, and none fatal. CONCLUSIONS: (1) Changes in management plan may occur in the majority of patients based on EUS results. (2) The management changes are often of major importance with regard to health care costs and safety, and are more often in the direction of less costly, risky, and invasive management. (3) EUS is safe in experienced hands.
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OBJECTIVE: The objective of this study was a) to determine the plasma and red cell thiamin levels in geriatric outpatients and b) to evaluate, using the rat model, the sensitivity of plasma thiamin concentration as an indicator of nutritional status for this vitamin. SUBJECTS: Thirty geriatric outpatients were evaluated for their plasma and erythrocyte thiamin levels. METHODS: Plasma and red cell thiamin levels were determined by a microbiologic assay using kloeckera apiculata. Sprague-Dawley rats were fed a thiamin deficient diet. Blood samples were obtained on specified days and the plasma and erythrocyte thiamin levels determined. RESULTS: Forty-three percent of the subjects studied had plasma thiamin levels below 2 SD of the mean of the younger-age group (20-60 yr) while 57% had a plasma thiamin below 10 ng/ml (the lower reference range of the younger age group). Twenty-seven percent were found to have red cell thiamin levels below 2 SD of the mean of the younger-age group, while 33% had red cell thiamin levels below 138 ng/ml (the lower reference range of the younger-age group). The rat study indicated that plasma thiamin concentration is a sensitive indicator of the nutritional status for this vitamin. CONCLUSION: About 50% of geriatric outpatients in this study had low plasma thiamin levels. The long-term effect of a low plasma thiamin level on cognitive functions remains to be investigated.
Exposure of the human colon adenocarcinoma HT29 cells to different concentrations of 5-fluorouracil (5FU) for 24 h resulted in a dose-dependent increase in the cellular glutathione (GSH) level which remained elevated up to 72 h following 5FU treatment. Pretreatment of HT29 cells with 5FU was found to enhance the uptake of methotrexate (MTX) as compared to control cells. Administration of MTX 24 h after 5FU was found to be synergistic, whereas administration of MTX 24 h before 5FU or together with 5FU was not found to be synergistic. The results of this study suggest that the increase in cellular GSH level as a result of 5FU pretreatment may play a role in the enhancement of MTX uptake and the cytotoxicity of both drugs in HT29 cells.
BACKGROUND: Endosonography is a significant advance in the preoperative staging (TNM classification) of esophageal cancer. Its accuracy for evaluating depth of tumor invasion is over 80%. METHODS: A multicenter retrospective cohort study of patients with esophageal carcinomas defined to be invasive (T4) by endosonography was performed to compare the survival of surgically and nonsurgically treated patients. Median survival time, overall mortality, and Kaplan-Meier survival curves were compared by treatment group. Univariate and Cox regression analysis were used to evaluate the effects of various prognostic factors and treatment on the risk of death. RESULTS: A total of 79 patients were studied. The surgical group (Group I, n = 42) was significantly younger and had more distal tumors (adenocarcinomas) than the nonsurgical group (Group II, n = 37). Endosonography was significantly more accurate than CT scanning in identifying tumor invasion (87.5% versus 43.8%, respectively, p = .0002). Overall mortality rate was not significantly different between treatment groups; 59.5% of the surgical group and 64.9% of the nonsurgical group were dead at follow-up (p = 0.65). Similarly, the median survival times of Group I and Group II patients were similar (5.2 and 7.0 months, respectively, p = 0.50). Survival curves for the two groups were almost overlapping (log rank test, p = 0.84). Even after adjusting for age, histologic diagnosis, tumor location, and regional lymph node status, surgical treatment did not significantly influence survival (p = 0.24). CONCLUSIONS: Endosonography accurately identifies patients with invasive T4 tumors who have a poor prognosis. This prognosis is independent of mode of therapy.
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The effect of a diet containing 10-40% lyophilized cabbage or broccoli as cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male rats. The GSH levels of the duodenum mucosa and the liver were also measured. Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose-related manner; potato had no effect. All three vegetables had no effect on the liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given to rats during and after DMH injections had little or no effect on tumor incidence and total number of colon tumors. Tumors were larger in rats that received GSH than in those that received water. This study shows that the colon mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or broccoli and that GSH added to the drinking water did not affect DMH-induced colon tumorigenesis under the experimental conditions used.
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The effect of endotoxin on colon tumors was studied in male Sprague-Dawley rats. Colon tumors were induced in weanling rats by the administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). When colon tumors were detected by colonoscopy in 80% of the rats around week 24 after DMH injection, the animals were divided randomly into two groups. One group served as the control. The other group received six endotoxin (Escherichia coli) treatments every fifth day. The first dose was 50 micrograms/100 g (intraperitoneally); the remaining doses were 100 micrograms/100 g (subcutaneously). Rats were killed 2 weeks after the last endotoxin injection. Endotoxin treatments resulted in larger colon tumors. The median tumor size was 71 mm2 for endotoxin-treated and 31 mm2 for untreated rats (P less than 0.02). Endotoxin treatments also resulted in a significantly higher incidence (P less than 0.05) of ulcer development in the small intestine, that is 47% in the endotoxin-treated versus 23% in the untreated rats. After a single subcutaneous injection of endotoxin (100 micrograms/100 g), the colon mucosal reduced glutathione (GSH) level was raised by 21% at 16 hours, reached a peak on day 2, then decreased to baseline by day 4. The increased GSH level in the colon mucosa was maintained up to the third endotoxin injection. By the fifth injection, no increase in the GSH level was observed. These results suggest that the growth of colon tumors in rats induced by DMH could be enhanced by endotoxin treatments. The enhanced tumor growth may be due to an increase in the colon GSH level and/or other mediators released by macrophages as a result of endotoxin treatments.
The effect of DL-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis, on colon tumor development was studied in rats. Weanling male Sprague-Dawley rats were randomly assigned to one of three groups following a week of adaptation. Group 1 rats received BSO (4.5 mM) daily in the drinking water one week before 1,2-dimethylhydrazine (DMH) injections and continued to receive BSO daily until sacrificed; group 2 rats received BSO (4.5 mM) after the last DMH injection, and continued to receive BSO daily until sacrificed; group 3 rats did not receive BSO. All experimental rats received 20 weekly subcutaneous injections of DMH (20 mg/kg body wt.) for colon tumor induction. The tumor incidence was lower in group 1 (54%) than in group 2 (97%) or group 3 (96%). The median tumor size is significantly smaller in group 1 (11 mm2) than group 3 (46 mm2). The group 2 had the largest median tumor size (65 mm2).