V. D'Onofrio

Long-term endoscopic surveillance of patients with Barrett's esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study.

OBJECTIVE:Barretts esophagus (BE) is a premalignant condition for which regular endoscopic follow-up is usually advised. We evaluated the incidence of esophageal adenocarcinoma (AC) in patients with BE and the impact of endoscopic surveillance on mortality from AC.METHODS:A cohort of newly diagnosed BE patients was studied prospectively. Endoscopic and histological surveillance was recommended every 2 yr. Follow-up status was determined from hospital and registry office records and telephone calls to the patients.RESULTS:From 1987 to 1997, BE was diagnosed in 177 patients. We excluded three with high-grade dysplasia (HGD) at the time of enrollment. Follow-up was complete in 166 patients (135 male, 31 female). The mean length of endoscopic follow-up was 5.5 yr (range 0.5–13.3). Low-grade dysplasia (LGD) was present initially in 16 patients (9.6%) and found during follow-up in another 24 patients. However, in 75% of cases, LGD was not confirmed on later biopsies. HGD was found during surveillance in three patients (1.8%), one with simultaneous AC; two with HGD developed AC later. AC was detected in five male patients during surveillance. The incidence of AC was 1/220 (5/1100) patient-years of total follow-up, or 1/183.6 (5/918) patient-years in subjects undergoing endoscopy. Four AC patients died, and one was alive with advanced-stage tumor. The mean number of endoscopies performed for surveillance, rather than for symptoms, was 2.4 (range 1–10) per patient. During the follow-up years the cohort had a total of 528 examinations and more than 4000 biopsies.CONCLUSION:The incidence of AC in BE is low, confirming recent data from the literature reporting an overestimation of cancer risk in these patients. In our patient cohort, surveillance involved a large expenditure of effort but did not prevent any cancer deaths. The benefit of surveillance remains uncertain.

Long-term follow-up of achalasia patients treated with botulinum toxin.

AIMS To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.

Antibody response to Helicobacter pylori CagA and heat-shock proteins in determining the risk of gastric cancer development

OBJECTIVE To investigate whether the systemic antibody response to Helicobacter pylori heat shock protein B can be considered, in addition to anti cytotoxin-associated protein [CagA) antibody determination, a further serological marker of increased risk of gastric cancer development. METHODS A total of 98 Giemsa positive Helicobacter pylori patients (28 with gastric cancer, 30 with duodenal ulcer and 40 with nonulcer dyspepsia) were studied. Serum samples obtained from all patients were tested for IgG antibodies to CagA (116 kDa), VacA [89kDa) and heat skock protein B (54 kDa) antigens of Helicobacter pylori by the Western blot technique. RESULTS 26/28 patients [(92.9% with gastric carcinoma, 29/30 patients [96.7%) with duodenal ulcer and 30/40 patients (75.0%) with non-ulcer dyspepsia were seropositive for CagA protein. The prevalence of serum IgG antibody to CagA in the cancer patients was not significantly higher than in duodenal ulcer and non-ulcer dyspepsia patients. The prevalence of antibodies to VacA was not significantly different between gastric carcinoma and non-ulcer dyspepsia patients. In contrast the prevalence of systemic antibodies to heat skock protein B was significantly higher in gastric cancer patients (78.6%) than in duodenal ulcer (36.7%, p=0.002) or nonulcer dyspepsia patients (52.5%, p=0.029). CONCLUSIONS The detection of antibodies to heat shock protein B is proposed as an additional test which, in association with the determination of serum antibodies to CagA, could help in determining the risk of developing severe gastroduodenal disease, and gastric cancer, in particular.

Gastroprotection by 4-Methylpyrazole Against Ethanol in Humans

Abstract4-Methylpyrazole (4-MP), a specific inhibitor ofalcohol dehydrogenase, exerts gastroprotection ofunusually long duration in rats. We tested thehypothesis that pretreatment with 4-MP might protect the human gastric mucosa against alcohol-inducedacute injury. Fourteen healthy volunteers receivedpretreatment with either 4-MP, 15 mg/kg body weightdissolved in 50 ml of orange juice, or placebo and 2 hr later 100 ml of 40% ethanol. The endoscopicappearance of the gastric mucosa was evaluated andscored (scale 0-5) and mucosal biopsies were obtainedjust before pretreatment and 30 min after ethanol for histologic examination and prostaglandinE2 measurement. In the 4-MP group the meanendoscopic injury score was significantly lower thanthat in placebo group, in both the body and the antrum.Histologically, 4-MP significantly reduced disruption ofsurface epithelium and completely prevented the deephemorrhagic mucosal lesions. In the 4-MP group nochanges in gastric mucosal PGE2 levels weredetected. In rats, 4-MP did not inhibit gastric acid output,whereas it markedly increased the adherent gastric mucusevaluated by the alcian blue recovery method. When lipidperoxidation was induced by carbon tetrachloride in hepatic microsomes, 4-MP caused significantinhibition of malondialdehyde generation. We concludethat 4-MP provides significant protection of the humanstomach against alcohol-induced acute mucosal injury. 4-MP, besides inhibiting the conversionof alcohol to acetaldehyde, might protect the gastricmucosa by increasing adherent gastric mucus and byscavenging free radicals.

Association between coffee or tea drinking and Barrett’s esophagus or esophagitis: an Italian study

Background/Objectives:Only a few papers have treated of the relationship between Barrett’s esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence.Subjects/Methods:Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire.Results:BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33–10.6; >1: OR=3.79, 95% CI 1.31–11.0; test for linear trend (TLT) P=0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43–12.3; TLT P=0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19–16.2; TLT P<0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15–17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00–3.43).A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P<0.05) was observed in tea drinkers.Conclusions:Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

Alcohol consumption pattern and risk of Barrett's oesophagus and erosive oesophagitis: an Italian case-control study

Knowledge about the association between alcohol and Barretts oesophagus and reflux oesophagitis is conflicting. In this case-control study we evaluated the role of specific alcoholic beverages (red and white wine, beer and liquors) in 339 Barretts oesophagus and 462 oesophagitis patients compared with 619 endoscopic controls with other disorders, recruited in twelve Italian endoscopic units. Data on alcohol and other individual characteristics were obtained from structured questionnaires. No clear, monotonic significant dose-response relationship was pointed out for red wine. However, a generalised U-shaped trend of Barretts oesophagus/oesophagitis risk due to red wine consumption particularly among current drinkers was found. Similar results were also found for white wine. Liquor/spirit consumption seemed to bring about a 1·14-2·30 risk excess, although statistically non-significant, for current Barretts oesophagus/oesophagitis drinkers. Statistically significant decreasing dose-response relationships were found in Barretts oesophagus for frequency and duration of beer consumption. Similar, but less clear downward tendencies were also found for oesophagitis patients. In conclusion, although often not statistically significant, our data suggested a reduced risk of Barretts oesophagus and oesophagitis with a low/moderate intake of wine and beer consumption. A non-significant increased risk of Barretts oesophagus/oesophagitis was observed with a higher intake of any type of heavy alcohol consumption, but no conclusion can be drawn owing to the high number of non-spirit drinkers and to the small number of drinkers at higher alcohol intake levels.

M1108 Capsule Endoscopy Is Useful and Safe for Small Bowel Surveillance in Familial Adenomatous Polyposis

Results: Eleven of 23 patients with FAP had duodenal polyps. During CE, jejunal-ileal polyps were detected in 7 of 23 FAPs, with a total number of 15 polyps in the ileum. The presence of duodenal adenomas was the only clinical feature predictive of small-bowel polyps. Identification of the ampulla of Vater was not achieved with CE; duodenal polyps were only seen in 4 of 11 patients identified endoscopically, with an underestimation of polyp numbers. APC mutations between codons 499 and 805 were associated with the absence of small-bowel polyps. Conclusions: CE is useful and safe for the surveillance of jejunal-ileal polyps in selected patients with FAP. CE is not useful in the surveillance of the duodenum where the majority of small-bowel cancers occur. (Gastrointest Endosc 2008;67:61-7.) Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disease; the gene locus is on chromosome 5q21. 1-3 The disease is characterized by adenomatous polyps in the large and small bowels and is associated with a virtual 100% risk of colorectal cancer.