The use of thiopurines for the treatment of inflammatory bowel diseases in clinical practice.

BACKGROUND: Thiopurines are the most commonly used immunomodulatory drugs in inflammatory bowel diseases. AIM: To evaluate the use, the therapeutic and safety profiles of thiopurines in a large sample of IBD patients. METHODS: We reviewed 3641 case histories of IBD patients. Thiopurines were prescribed in 582 patients (16.0%); the analysis was performed on the 553 (267 ulcerative colitis, 286 Crohn's disease) with exhaustive clinical data. RESULTS: The main indications for treatment were steroid-dependence (328/553, 59.3%) and steroid-resistance (113/553, 20.7%). Thiopurines were started when CD were younger than UC patients (p<0.001) but earlier from diagnosis in UC than in CD patients (p=0.003). Efficacy was defined as optimal (258/553, 46.6%), partial (108/553, 19.5%), absent (85/553, 15.4%) and not assessable (102/553, 18.4%). Efficacy was independent of disease type, location/extension or duration and age at starting. Side effects were observed in 151/553 (27.3%) patients, leading to drug discontinuation in 101 (18.3%). 15 out of the 130 (11.5%) patients who took thiopurines for more than 4 years relapsed, more frequently in CD than in UC (OR=3.67 95% C.I. 0.98-13.69; p=0.053). CONCLUSIONS: Thiopurines confirm their clinical usefulness and acceptable safety profile in managing complicated IBD patients. The majority of patients treated for longer than 4 years maintain response. No clinical and demographic predictive factors for efficacy and side effects were identified.

Intraepithelial carcinoma of the oesophagus: report of 25 cases from north-east Italy.

OBJECTIVE: To investigate the incidence and define the diagnostic aspects of intraepithelial squamous cell carcinoma of the oesophagus and to show the trend in its natural history. DESIGN: Analysis of records of more than 31000 upper gastrointestinal endoscopies in a secondary referral centre. SETTING: Gastroenterology unit, Italy. SUBJECTS: 23 men and 2 women with endoscopic and histological diagnoses of intraepithelial squamous cell carcinoma of the oesophagus. RESULTS: The incidence was 0.8/1000 patients/year. There was a coexisting oropharyngeal or laryngeal cancer in 17 patients. The endoscopic appearance was of a more or less well-defined hyperaemic area. Lesions progressed to infiltrating carcinoma in a mean of 18.3 months range 11-32). CONCLUSIONS: Intraepithelial squamous cell carcinoma is rare in this population. Endoscopy and histology are essential for diagnosis and staging.

Ethanol metabolism and aging: the role of "first pass metabolism" and gastric alcohol dehydrogenase activity.

To investigate the effect of age and gender on ethanol metabolism, first-pass metabolism (FPM) and gastric alcohol-dehydrogenase (ADH) activity were compared in 32 elderly and 30 young adult nonalcoholic subjects. The FPM was obtained from the difference between the area under the curve of ethanol blood concentration after intravenous or oral administration of ethanol 0.3 g/Kg b.w. The ADH activity was determined in samples of gastric mucosa obtained during diagnostic endoscopy. In the young adult group the FPM was higher in men than in women (3.3 +/- 2.3 vs 1.2 +/- 0.9 mmol/l/h, respectively, p < .01). In aged subjects FPM was found to be very low for men (1.1 +/- 0.8 mmol/l/h, p < .001); conversely, FPM was not significantly reduced in women (1.7 +/- 0.8 mmol/l/h, p = n.s.). The gastric ADH activity was significantly (p < .01) higher in young adult men than women, whereas in aged subjects the activities were low (p < .0001) in both sexes. Thus, gender-related FPM differences equalize in the elderly or are even reversed, most likely because of gastric mucosal atrophy, which occurs more in men than women.

Effects of omeprazole on ethanol metabolism: an in vitro and in vivo rat and human study.

Since some H2-receptor antagonists, like cimetidine or ranitidine, affect ethanol metabolism by interference with gastric and/or hepatic alcohol dehydrogenase (ADH) it was investigated whether omeprazole has a similar effect and its effects were compared with those of cimetidine, an inhibitor of gastric ADH. The first-pass metabolism (FPM), quantified by measuring the difference between areas under the curve (AUC) of ethanol blood concentrations after oral intake or intravenous administration of the same amount (0.3 g kg-1 b.w.) of ethanol (EtOH), was studied before and after 1 week of omeprazole (20 mg daily) or cimetidine (800 mg daily) administration in 10 normal male volunteers. ADH activity was determined in gastric mucosal samples, collected during endoscopy, before and after 1 month of omeprazole treatment. The effect of the drugs on gastric and hepatic ADHs was studied in vitro in both rat and man. No significant effect of omeprazole was found on AUCs of the blood EtOH concentrations. The ADH activity in antral mucosa before and after omeprazole therapy did not show significant differences. In vitro, omeprazole reduced the activity of the low Km gastric ADH with a Ki of 5.6 mM in rat and the hepatic ADH activity with a Ki of 2.4 mM in man, whereas the drug did not show any effect on hepatic ADH in rat and gastric ADH in man. On the contrary, cimetidine increased the AUCs of EtOH blood concentrations after both gastric and intravenous route and, in the in vitro assay, inhibited gastric and hepatic ADH in both man and rat. These results indicate that omeprazole does not affect EtOH metabolism in man and seems to be safer than cimetidine in subjects unable to reduce ethanol intake during the therapy for peptic ulcer or other hypersecretory conditions.

Endoscopic injection sclerotherapy in non-variceal upper gastrointestinal bleeding. A comparative study of polidocanol and thrombin.

To date several agents have been used to achieve haemostasis in patients with non-variceal upper gastrointestinal bleeding using endoscopic sclerotherapy techniques. Polidocanol has been widely used but local complications have been reported after treatment. We have compared the efficacy and safety of thrombin and polidocanol in 82 consecutive patients with ongoing or recent bleeding from duodenal, gastric, or anastomotic ulcers. Primary control of haemostasis from spurting vessels was achieved in 90% of cases using polidocanol and in 86.6% using thrombin. Definitive haemostasis was obtained in 80% of patients in both groups. When a non-bleeding vessel was visible, injection of polidocanol or thrombin effectively prevented rebleeding in 90.9% and 85.7% of cases, respectively. When a non-bleeding sentinel clot was present, injection of polidocanol or thrombin provided definitive haemostasis in 100% and 92.8% of cases, respectively. No statistically significant difference was evident between the two agents. In the polidocanol group, one local haemorrhagic complication was noted. No general or local complications were recorded in the thrombin group.

Fiberoptic endoscopic resection of symptomatic leiomyoma of the upper esophagus. Case report.

A symptomatic leiomyoma of the upper esophagus was successfully removed through a fiberoptic endoscope in an 84-year-old man. Endoscopic resection via flexible endoscope may be considered as an option in treating selected cases of esophageal leiomyoma and for high surgical risk patients.

[Environmental risk factors in the pathogenesis of peptic ulcer. The role of cigarette smoke]. / Fattori di rischio ambientali nella patogenesi dell'ulcera peptica. Il ruolo del fumo di sigaretta.

Smoking habit has been evaluated in 108 patients with gastric or duodenal ulcer diagnosed by endoscopy and in a control group of 147 endoscopically normal subjects. We found a positive association for both the gastric and duodenal ulcer (relative risk of 3.5). Furthermore, an increasing risk was associated both with the duration of smoking and with the amount of cigarettes smoked daily. Conversely, no significant association was demonstrated between peptic ulcer and the more os less precocious age at starting smoking or with the nicotine and tar content of the cigarettes usually smoked. Among ex-smokers, an increasing risk (relative risk of 2.0) was observed for gastric ulcer only.

Squamous cell papilloma of the esophagus. Report on 35 endoscopic cases.

We herein report our experience of 35 cases of esophageal squamous cell papilloma (ESP), diagnosed among 8,095 consecutive upper gastrointestinal endoscopies, and histologically confirmed. The incidence (0.45%) was higher than previously reported. Macroscopically, ESP presented with several distinctive features, thus endoscopy permitted great diagnostic accuracy. Most of the papillomas were located in the middle-third of the esophagus, and no significant association with hiatal hernia and reflux esophagitis was seen. The lesion did not recur after removal either by forceps or by diathermic snare.