The Veneto Region's Barrett's Oesophagus Registry: aims, methods, preliminary results.

BACKGROUND: The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. AIMS: The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. METHODS: An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. RESULTS: In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female=3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients (p<0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e., progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. CONCLUSION: A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.

Esophageal hyperalgesia in patients with ulcerative colitis: role of experimental stress.

OBJECTIVES: Intestinal inflammation is associated with enteric nervous system alterations, at both inflamed and noninflamed sites. The perception of stimuli from the GI tract is enhanced during inflammatory conditions, but it is unknown whether visceral hypersensitivity is limited to the inflamed area or diffuse throughout the entire GI tract. Moreover, although stress can reactivate inflammatory processes in the gut, it is unknown if this can alter perception from the GI tract. Our aim was to determine if patients with ulcerative colitis (UC) have increased esophageal sensitivity to distention and whether this is modified by experimental stress. METHODS: Ten UC patients and 12 healthy volunteers (HVs) underwent gradual balloon distension of the esophagus to assess their visceral sensitivity. Perceptive and pain thresholds were evaluated in basal conditions and after induction of experimental stress (cold water pressure test) while blood pressure and heart rate were monitored. RESULTS: Patients with UC had perceptive thresholds to distension similar to HVs (14.8+/-2.0 ml of air vs 14.5+/-3.0 ml); in contrast, the volume increment needed to evoke pain was significantly lower in UC patients than in HVs (58.9% vs 149.9%, p < 0.05). Physical stress caused a similar decrease in perceptive thresholds in HVs (-29.1+/-8.4%) and patients (-17.7+/-9.1%), but pain thresholds were significantly decreased only in HVs (-28.3+/-7.1% vs -11.5+/-12.3%). CONCLUSIONS: UC is characterized by increased esophageal sensitivity, indicating the existence of diffuse hyperalgesia during intestinal inflammatory processes. This increased sensitivity may account for the frequent upper GI symptoms these patients complain of when in clinical remission.

Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation.

AIMS: To assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study. METHODS: After an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70 patients suffering from chronic constipation (58 females, aged 42 (15) years) with normalised bowel frequency (>3 bowel movements (bm)/week) were randomly allocated to receive either PMF-100 or placebo, contained in sachets (one sachet in 250 ml of water twice daily) for 20 weeks. Patients were assessed at four week intervals, and reported frequency and modality of evacuation, laxative use, and relevant symptoms on a diary card. At weeks 1, 12, and 24, a physical examination and laboratory tests were performed. RESULTS: Complete remission of constipation was reported by a significantly (p<0.01) higher number of patients treated with PMF-100 compared with placebo at each four week visit. At the end of the study, 77% of the PMF-100 group and 20% of the placebo group were asymptomatic. Compared with placebo, patients treated with PMF-100 reported hard/pellety stools and straining at defecation less frequently, a significantly higher bowel frequency (week 12: 7. 4 (3.1) v 4.3 (2.5) bm/week, 95% CI 1.64, 4.42; week 24: 7.4 (3.2) v 5.4 (2.1) bm/week, 95% CI 0.13,3.93), reduced consumption of laxative/four weeks (week 12: 0.7 (2.7) v 2.2 (3.3), 95% CI -2.29, 0. 03; week 24: 0.2 (0.8) v 1.4 (2), 95% CI -2.07, -0.023), reduced mean number of sachets used (week 12: 33 (13) v 43 (12), 95% CI -17. 24, 4.56; week 24: 33 (13) v 44 (12), 95% CI -19.68, -2.24), and reduced number of drop outs for therapy failure (16 v 3; p<0.005). Adverse events, physical findings, laboratory values, palatability, and overall tolerance of the solutions did not differ between groups. CONCLUSIONS: Administration of small daily doses of isosmotic PEG electrolyte balanced solutions was effective over a six month period for the treatment of functional constipation. A mean daily dose of approximately 300 ml of PEG solution (PEG 17.52 g) appeared to be safe, well tolerated, and devoid of significant side effects.

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.

AIM: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. METHODS: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. RESULTS: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01). CONCLUSIONS: Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

Teaching gastroenterology using the problem-based learning method.

The need to change the methods of teaching medical students has become self-evident in the past two decades, and strategies for revision are indicated in the new course curriculum, Tabella XVIII. A modern teaching method is the problem-based learning (PBL) method, which has already been adopted by over 100 medical schools throughout the world. This method can also be a satisfactory tool for teaching gastroenterology to undergraduate students, and its implementation requires only a few resources that are available in most universities. The theoretical principles of the method are illustrated and practical suggestions are given to set up a course in gastroenterology using this method.

[Measurement of gastric emptying with Tc 99m. Technique and reliability of the test]. / Misurazione del tempo di svuotamento gastrico con 99mTc. Tecnica di attuazione e affidabilità del test.

Among the various methods used to measure gastric emptying time, scintigraphy is nowadays the technique of choice. Since only few data are available on the operative characteristics of the method, the authors investigated reproducibility, sensitivity, and specificity of a modified scintigraphic technique for the measurement of gastric emptying time. Three groups of subjects--healthy volunteers, patients with functional dyspepsia, and patients with upper gastrointestinal conditions--were administered liquid meals having various standard consistencies (349 tests on the whole). In both healthy volunteers and dyspeptic patients the method had high sensitivity (72%), good specificity (69%), and low intra-subject variation (25%). In all cases, the increase in meal density produced a delay in gastric emptying. Dyspeptic patients had slow gastric emptying of high-fiber meals, while in duodenal ulcer and in atrophic gastritis emptying was significantly faster. The radionuclide method proved valuable in measuring gastric emptying and was useful to confirm the pathogenesis of the various conditions. As for functional and organic pathologic conditions, it allowed treatment efficacy to be evaluated.

Psychological stress and gastric emptying in normal subjects.

Gastric emptying half-time was measured in 10 healthy volunteers on two different occasions over a one-week interval, with an identical test meal. The first was the control evaluation, and at the second assessment, psychological stress was induced by the technique of dichotomous listening. Psychological and physiological parameters were assessed before and during the test period. No significant or consistent modifications of gastric-emptying time were induced by the stress procedure. Looking at individual subjects instead of mean values, gastric emptying was unchanged in 5 subjects, slower in 3, and faster in the remaining 2. These 3 groups had different mean values on two subscales of the Sixteen Personality Factor Questionnaire.

[Collection, survey and interpretation of pH-metry data]. / Rilievo, acquisizione ed elaborazione del dato pH-metrico.

24-hour oesophageal pH monitoring is a necessary tool to diagnose Gastro-Oesophageal Reflux Disease. The technical characteristics of the available equipments have been improved and standard criteria to identify reflux episodes have been defined, increasing the sensitivity and specificity of the test. The state of the art on the technical features of prolonged pHmetry will be reviewed in this paper.

Eosinophilic gastroenteritis: report of two atypical cases.

Eosinophilic Gastroenteritis (EG) is a poorly understood disorder defined by eosinophilic infiltration of the bowel wall, eosinophilia and gastrointestinal symptoms. The disease's aetiology, course and treatment are not well known. We report two atypical cases of EG: one involving the mucosal layer and another involving the serosal and muscularis layer. The first shows how EG may present with a long history of episodes of intestinal obstruction and malabsorption and how the disease could take a severe course and may be unresponsive to treatment. The second case shows EG presenting as acute abdomen and which subsequently became asymptomatic without therapy, regardless of the fact that peripheral eosinophilia remained present. This case raises the problem of how to treat an asymptomatic patient, what parameters should be considered in order to assess the progress of the disease and the indications for treatment.

[Bleeding of gastric ulcers. Epidemiologic, clinical and functional characteristics]. / Il sanguinamento da ulcera gastrica. Caratteristiche epidemiologiche, cliniche e funzionali.

The frequency of gastrointestinal haemorrhage due to gastric ulcer has been assessed in 254 personally observed patients suffering from this endoscopically verified pathology. 56 patients, namely 22% of the cases, presented haematemesis and/or melena of the ulcerative lesion. This subgroup was compared with 65 patients with endoscopically verified gastric ulcer without previous bleeding episodes from the lesion in their clinical history, in respect of certain epidemiological, clinical and biohumoral features. The purpose of the study was to check the possible existence of clinical and/or physiopathological differences between subjects with bleeding gastric ulcer and the population of non-bleeding ulcer patients. In 80% of patients studied, the gastric ulcerous disease started with digestive haemorrhage and it was not accompanied by dyspeptic-painful symptomatology in 20% of cases. The pain symptomatology does not appear to be influenced by the intake of non-steroid anti-phlogistic drugs. No significant difference emerges between the two groups considered as regards epidemiological features and biohumoral data (PG I, gastrin, B.A.O. and M.A.O.).

Cholestatic jaundice as the presenting symptom of small cell lung cancer.

Small-cell lung cancer is an infrequent (10%) form of lung cancer which may rarely become apparent with signs of distant metastases. A case is presented where a cholestatic syndrome was the presenting feature of a small-cell lung cancer which was not suspected clinically. The misleading clinical picture, the inaccurate results of ultrasound, ERCP and chest x-ray did not allow the correct diagnosis to be made until post mortem examination. Even according to the published experience, which is reviewed here, this presentation and clinical course appear exceedingly rare.

[Development of gastric carcinoma at the site of a preceding peptic ulcer after 10 years]. / Sviluppo di un carcinoma gastrico nella sede di una precedente ulcera peptica dopo 10 anni.

We have observed an adenocarcinoma of the stomach which developed on the site where an apparently benign active gastric ulcer had been diagnosed radiologically 10 and 7 years previously. The patient had complained of recurrent episodes of epigastric pain over ten years, which were well controlled by the medical treatment. The length of clinical history in this patient makes it unlikely that his ulcer was neoplastic at the time of onset. This appears to be, therefore, one of the rare instances of development of a gastric carcinoma on the site of a previously benign peptic ulcer.

DSM-III diagnoses associated with dyspepsia of unknown cause.

The frequencies of DSM-III diagnoses in 30 patients with dyspepsia of unknown origin and 20 patients with organic dyspepsia were compared. Dyspepsia of unknown origin was associated with a higher prevalence of psychiatric diagnoses (86.7% versus 25.0%), particularly anxiety disturbances (66.7%).

Evaluation of the hydrogen breath test in man: definition and elimination of the early hydrogen peak.

After ingestion of a non-absorbable carbohydrate breath hydrogen excretion increases early at about 10 minutes, and again later when the ingested carbohydrate enters the caecum. The late rise has been used as a marker of mouth to caecum transit time, but the source of the early rise has not been satisfactorily explained. We studied in 60 healthy volunteers the source and frequency of the early rise in breath hydrogen after ingestion of a non-absorbable carbohydrate. After ingestion of either lactulose solution (10 g in 150 ml water), lentil soup (46 g carbohydrate) or solid meal containing baked beans (15 g carbohydrate), breath hydrogen was significantly raised above basal concentrations within 10 minutes (81 +/- 27, 395 +/- 138 and 110 +/- 52% above basal respectively). A significant rise in breath hydrogen (75 +/- 21%) occurred 10 minutes after sham lactulose feeding (lactulose applied to oral cavity but not swallowed), but no early peak occurred after sham saccharin feeding (non-fermentable carbohydrate), intragastric or intraduodenal administration of lactulose. Ten of the 12 subjects given lactulose sham feeding were restudied after oral hygiene with chlorhexidine mouthwash. In these the early hydrogen peak was abolished. Oral hygiene also reduced the occurrence and magnitude of the early hydrogen rise after lactulose ingestion. These findings indicate that the early rise in breath hydrogen observed after ingestion of lactulose is produced by interaction with oral bacteria.

[Methodological aspects of gastric acid examination]. / Aspetti metodologici del sondaggio gastrico.

The aim of the present work was to study gastric acid secretion in control subjects and in gastric and duodenal ulcer patients and to evaluate sex, age, body weight, blood group, cigarette smoking and the intake of H2-blockers in the 24 hours preceding gastric acid analysis. The results obtained seem to indicate that 6 micrograms/kg b.w./i.m. Pentagastrin is the best stimulus and that basal secretion may be assessed in thirty minutes, without altering the BAO value. Factors such as cigarette-smoking and H2-blockers intake on the one hand and body weight and male sex on the other influence gastric juice output and should therefore be considered in interpreting the results.