Gabriella Lapertosa

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.

Risk factors for Barrett's esophagus: A case-control study

Barretts esophagus (BE) is an acquired disorder due to chronic gastroesophageal reflux. Environmental factors seem to play an important role in the pathogenesis of BE, especially in Western society. A multicenter case‐control study was carried out between February 1995 and April 1999 in 8 Italian Departments of Gastroenterology gathered in a study group (GOSPE), in order to analyze the influence of some individual characteristics and life‐style habits on the occurrence of BE. Three groups of patients were studied: 149 patients with BE, 143 patients with esophagitis (E) and 308 hospital controls (C) with acute, non‐neoplastic, non‐gastroenterological conditions. The diagnosis of BE was based on endoscopy and histology. E was defined by the Savary classification (grade I–III). Data collection was performed by using a questionnaire that focused on smoking, coffee and alcohol consumption, medical history, drugs history, gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation) and socio‐economic status. Multivariate analysis showed that the frequency of weekly GERD symptoms was significantly associated with both BE and E (p<0.0001), such as the presence of hiatal hernia (p≤0.001). Ulcer was significantly associated with BE (p=0.001). Among patients with E, the risk was directly related to spirits consumption (p=0.03). Patients with GERD symptoms that lasted more than 13 years were more likely to have BE than E (p=0.01). In conclusion, results from our study point out that long‐standing GERD symptoms, hiatal hernia and possibly alcohol consumption are risk factors in the development of the BE and E.

Chronic hepatitis induced by Jin Bu Huan

BACKGROUND/AIMS Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

Primary signet‐ring carcinoma of the large bowel report of nine cases

Nine cases of signet‐ring carcinoma have been observed from among 800 consecutive histologic cases diagnosed as adenocarcinoma of the colon during a period of 10 years (0.9%). This group of nine patients (Group A) has been matched for sex, age, and stage with a group of 45 patients affected by oridinary carcinoma of the colon (Group B). Clinical and histologic parameters, including symptoms, primary tumor site, free interval from primary surgery, histochemical investigation of intracytoplasmic mucins, and survival, were evaluated. The results of this investigation showed no clinical differences between signet‐ring carcinoma and ordinary carcinoma, and no statistically significant results were observed regarding the frequency of local recurrence and actuarial survival.

Incidence of Barrett's adenocarcinoma in an Italian population : an endoscopic surveillance programme

Background: Barretts oesophagus is a premalignant condition leading to adenocarcinoma. The incidence of adenocarcinoma of the oesophagus and the gastro‐oesophageal junction is rapidly increasing in the USA, northern and central Europe. Data from southern Europe are still unavailable. Objective: To evaluate the incidence of oesophageal adenocarcinoma in a large cohort of Italian patients with Barretts oesophagus. Methods: A total of 344 patients (253 males and 91 females, age range 19‐75 years) with histologically proven Barretts oesophagus (length of metaplasia ≥3cm) were enrolled from November 1987 to June 1995. Endoscopic and histological examinations were scheduled at yearly intervals. Results: One hundred and eighty‐seven patients complied with the follow‐up. The mean duration of the follow‐up period was 36 months (total follow‐up 562 patient‐years; range 12‐90 months). Low grade dysplasia was found in five patients at the initial examination. During the surveillance period, dysplasia increased in frequency as well as in severity and was found exclusively in the intestinal type of Barretts oesophagus. In all, dysplastic changes were found in seven patients (five low grade and two high grade) and adenocarcinoma developed in three patients during the follow‐up. In a single case, both adenocarcinoma and specialized columnar epithelium developed without any evidence of dysplasia or intestinal metaplasia at the previous follow‐up examination. This prospective study shows an incidence of adenocarcinoma in Barretts oesophagus of 1/187 patientyears. When only patients with specialized columnar epithelium were considered, the risk of adenocarcinoma was 1/88 patient‐years. Conclusion: The present report shows that the incidence of adenocarcinoma in Italian Barretts oesophagus patients is in the range of that reported from other Western countries.

Barrett's esophagus: an update

Barretts esophagus (BE) is a complication observed in a small subset of patients with chronic gastroesophageal reflux. It is characterized by the presence of intestinal-type goblet cells in biopsies from the lower esophagus. The prevalence of BE increases with age, affecting 1% of the population older than 60 years. A genetic predisposition to reflux disease has been proposed. In a twin study of reflux disease, concordance was greater in monozygotic than dizygotic twins. An association between BE and esophageal adenocarcinoma, the incidence of which has increased remarkably in the last few decades, has been established. Esophagogastric junction cancers can arise from small areas of cardia intestinal metaplasia (CIM). Regular endoscopic and histologic follow-up of BE patients is recommended. Surveillance of patients with CIM is not advised. Chromoendoscopy may help to detect areas of high-grade dysplasia (HGD). The ablation of BE, e.g. by PDT or argon plasma coagulation, is not yet proven to reduce the cancer risk. Esophagectomy is still the standard management of HGD. Endoscopic mucosal resection may be used for visible, localized lesions with HGD, and this technique may be combined with thermal ablation for areas of HGD without visible abnormality.

Interferon therapy in chronic hepatitis C : evaluation of a low dose maintenance schedule in responder patients

Evidence has accumulated that interferon therapy can be effective in reducing transaminase levels and improving liver histology in patients with chronic hepatitis C. Unfortunately, the relapse rate after discontinuing treatment remains a problem. In this study the efficacy of a low dose of interferon was investigated for preventing relapses in patients who completely responded to a 6-month course of 3 MU 3 times a week. Eighteen out of 30 patients (60%) had normal ALT at the end of the 6th month of therapy. These patients were randomly allocated to receive either 1 MU interferon 3 times a week for 6 months or no treatment. Three patients (33.3%) without maintenance schedule and 4 (44.4%) treated with 1 MU relapsed. HCV-RNA was positive in 23 tested patients at entry and became undetectable in patients with sustained response. Relapse was associated with RNA reappearance. A post-therapy liver biopsy, performed in 8 patients, showed Knodells score improvement. In conclusion, our study confirms the efficacy of interferon at the dose of 3 MU 3 times a week for 6 months. A low maintenance dose of interferon seems to be ineffective in preventing relapse in patients with chronic HCV infection who have responded to a prior treatment course.

Gastroesophageal reflux disease : Relationship between clinical and histological features

Our purpose was to evaluate the relationshipbetween the clinical and histological features in acohort of patients who had gastroesophagealreflux-related lesions diagnosed after upper digestiveendoscopy. In all, 589 patients scheduled for electiveendoscopy in a multicentric prospective study wereevaluated. Multiple biopsies from the distal esophagusshowing aspects of esophagitis or metaplastic epithelium were taken. Esophagitis was histologicallydetected in 25.6%, gastric-type Barretts esophagus in36.2%, and specialized columnar epithelium in 33.1%. Thefrequency of esophagitis was constant across age decades. Patients with specialized columnarepithelium were significantly older (P = 0.01) and hada greater extent of metaplastic epithelium (P <0.0001). Specialized columnar epithelium was observed in 15% of patients with only distalesophagitis. In conclusion, endoscopic esophagitis wasconstant across age strata. The presence of specializedcolumnar epithelium was associated with older age andwith longer segments of Barretts esophagus. Shortareas of esophagitis should be biopsied in view of theirpotential for holding areas of specialized columnarepithelium.

24-hour Gastric pH and extent of duodenal gastric metaplasia in Helicobacter pylori-positive patients

BACKGROUND & AIMS Gastric metaplasia (GM) is essential to explain duodenal colonization by Helicobacter pylori. It seems to be acid induced but also occurs in H. pylori-positive patients with nonulcer dyspepsia (NUD), who are not acid hypersecretors. The aim of this study was to assess the circadian gastric acidity of 47 patients with duodenal ulcers (DUs) and 32 patients with NUD, both H. pylori positive, and its correlation to duodenal GM extent. METHODS H. pylori was detected by histology and CLOtest, and GM was diagnosed and graded on four bulb biopsy specimens. Each patient underwent 24-hour gastric pH-metry, and the relation between gastric pH and GM extent was assessed by factorial analysis. RESULTS Gastric pH was greater in patients with NUD than in patients with DU during 24 hours, night and daytime (P < 0.03-0.005). Gastric pH differed significantly (P < 0.0002) in relation to GM extent between the two populations, whereas no difference was found among the pH values of GM degrees. A significant increase in 24-hour gastric pH was associated with greater GM in patients with DU, whereas the opposite occurred in patients with NUD (P < 0.007). CONCLUSIONS The lower gastric acidity in patients with NUD than in patients with DU and the lack of correlation between gastric pH and the various GM degrees in the two H. pylori-positive populations suggest that gastric hyperacidity is not associated with duodenal GM.

Mucin profiles in the mucosa adjacent to large bowel non-adenocarcinoma neoplasias

Morphological features and mucin secretion patterns were investigated in the colonic mucosa adjacent to or overlying mesenchymal or primary epithelial neoplasias, other than adenomas and adenocarcinomas. The material included 15 cases of non‐adenocarcinoma tumours examined during 1978–1981. Increased sialomucins and morphological features similar to those described in the so‐called ‘transitional’ mucosa adjacent to primary colorectal adenocarcinomas were observed in only two cases. In contrast our previous studies have demonstrated ‘transitional’ profiles in 98% of adenocarcinomas.