p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.

AIMS: To investigate the immunohistochemical expression of p53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours. METHODS: Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. RESULTS: Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium. CONCLUSION: This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis.

Analysis of N-nitrosamines by high-performance liquid chromatography with post-column photohydrolysis and colorimetric detection.

N-Nitrosamines eluted from reversed-phase HPLC were quantitatively photohydrolysed in a UV photoreactor in aqueous solution to give the nitrite ion which could be determined colorimetrically with the Griess reagent. The chromatographic behavior of N-nitroso compounds (including 19 volatile dialkyl and 7 non-volatile N-nitrosamines) was studied on three octadecylsilane columns. The capacity factor varies linearly with the number of carbons atom of the n-dialkyl chains. N-nitrosamines bearing di-n-alkyl chains with the same number of carbon atoms could be separated with a highly polar mobile phase. The yield of photohydrolysis depends upon pH and time of exposure under UV light. The response was shown to be linear in the 0-200 ng range with a limit of detection of 8 pmoles injected for N-dialkyl nitrosamines. This limit was 20 pmoles for N-nitrosamines bearing two phenyl groups. Although N-nitrosamines could be detected at 230 nm without post-column reaction, such a reaction enhances the specificity of detection in biological matrices such as gastric juice or alcoholic beverages.

Double-blind comparison of pantoprazole and omeprazole for the treatment of acute duodenal ulcer.

OBJECTIVES: To compare the healing rates of acute duodenal ulcer in patients receiving pantoprazole 40 mg or omeprazole 20 mg once daily and to assess drug tolerance. DESIGN: Randomized, double-blind study evaluating patients with healed duodenal ulcer on endoscopy after 2 weeks of treatment and patients unhealed at 2 and after 4 weeks of treatment. SETTING: Hospital or private gastroenterology practice outpatients. PATIENTS: Men or women, aged at least 18 years, with one or two duodenal ulcers. Patients with ulcer complications or with other significant acid-related disease were excluded. A total of 270 patients entered the study, of whom 255 were included in the per-protocol analysis. RESULTS: The primary measure of efficacy was the healing rates of duodenal ulcers. Complete healing of ulcers was observed in 88 (71%) of the 124 patients in the pantoprazole group and in 85 (65%) of the 131 patients in the omeprazole group after 2 weeks of treatment. The cumulative healing rates after 4 weeks were 118 (95%) out of 124 and 117 (89%) out of 131 patients, respectively. There was no significant difference between treatment groups with respect to either healing rates or freedom from ulcer pain at 2 weeks. Both treatments were well tolerated: only 10 and 11 patients in the pantoprazole and omeprazole groups, respectively, reported adverse events. Diarrhoea was reported by two patients in each group. CONCLUSIONS: Pantoprazole 40 mg daily and omeprazole 20 mg daily are equally effective in inducing ulcer healing.

Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas.

OBJECTIVE: To compare incidence rates and epidemiological characteristics of acute upper gastrointestinal haemorrhage (AUGIH) in France with those of other European studies. DESIGN: Population-based multi-centre prospective survey. SETTING: 29 public hospitals and 96 private specialists in gastroenterology in four administrative areas in France during 1996. SUBJECTS: A total of 2133 AUGIH patients 18 years and over were included in the six-month study. OUTCOME MEASURES: Incidence and mortality. RESULTS: The overall incidence in France was 143 cases per 100000 persons per year, classified as out-patients (16%), emergency admissions (59%) and in-patients (25%). The incidence rates increased with age except for in-patients, and were higher in males. Peptic ulcer (36.6%), varices (13.7%) and erosive disease (12.3%) were the most frequent diagnoses. In 677 patients (31.7%), aspirin, antiinflammatory drugs or corticosteroids were taken on the 7 days before bleeding. The overall mortality (out-patients excluded) was 14.3% (10.7% for emergency patients and 23% for in-patients). Mortality was associated with comorbidities (especially malignancies, cirrhosis, asthma or respiratory deficiency), was lower in emergency patients using non-steroid anti-inflammatory drugs, and higher in in-patients using corticosteroids. CONCLUSIONS: In France, patients with AUGIH are frequently managed as out-patients. Gastrotoxic drug use is frequently associated with AUGIH and constitutes a strategic opportunity for preventive treatment. Discrepancies between countries are not clearly explained either by demographic factors or by drug use, but this may be related to the emphasis on AUGIH in in-patients.

[Polypoid pseudosarcomatous carcinoma of the esophagus. Report of two cases with favorable outcome after medical treatment]. / Carcinome pseudosarcomateux polypoïde de l'oesophage. Evolution favorable de deux cas traités médicalement.

The authors report two cases of esophageal polypoid pseudosarcoma with favorable outcome after endoscopic and medical treatment. Neither of the two patients could undergo general anesthesia. Endoscopic resection or monopolar electrocoagulation of the tumor was associated with chemotherapy and radiation therapy. A complete response of the tumor was observed in both cases. The two patients were alive and well with no evidence of recurrence or metastasis 3 and 5 years after diagnosis. Immunohistochemical study of those two tumors with monoclonal antibodies to intermediate filaments (keratin and vimentin) suggests duality in the spindle cell component. It may explain the biological behaviour of these particular cancers that have a better prognosis than other types of squamous cell carcinomas of the esophagus.

[Diagnosis of mediastinal neuro-endocrine tumor using endosonography guided transesophageal puncture biopsy]. / Diagnostic de tumeur neuro-endocrine médiastinale par ponction-biopsie transoesophagienne guidée sous échoendoscopie.

Histologic diagnosis of tumors of the mediastinum is mandatory for therapeutic management. The location and the variety of tumors are responsible for diagnostic difficulties. Endosonography guided fine-needle biopsy is an efficient and safe procedure for the diagnosis of peridigestive masses. We report the case of a patient with a neuroendocrine tumor of the mediastinum revealed by a mass syndrome. The diagnosis was performed by endosonography guided needle biopsy.

[Pancreatic sarcoidosis]. / Sarcoïdose pancréatique.

The authors report the case of a 30 year-old man with previous history of sarcoidosis, who presented with a painful infiltration of the pancreas. A review of the literature showed that symptomatic pancreatic sarcoidosis was uncommon, since only 8 other cases have been reported. Pancreatic involvement is frequently associated with hepatic infiltration (5/6 cases). Exocrine or endocrine dysfunction are possible. Diagnosis is made only at exploratory laparotomy. Prognosis is good. Steroid therapy is indicated in this peculiar type of pancreatitis, because of its long-range effectiveness on the outcome of the disease.

[Management of upper digestive hemorrhage occurring in the community: patterns of patient care in 4 French administrative areas]. / Prise en charge des hémorragies digestives hautes communautaires. Trajectoires des malades dans 4 départements français.

AIMS: To describe patterns of health care management in patients with upper gastrointestinal hemorrhage and to identify factors linked to the different patterns. PATIENTS AND METHODS: We conducted a prospective study of patients over 18 with upper gastrointestinal hemorrhage (inpatients excluded) among all public hospitals and private practice gastroenterologists in 4 French administrative areas (3 in Northern France and one in the South West). RESULTS: One thousand six hundred and two patients were included over a six-month period (1996). An endoscopic procedure was performed in 1532 patients in public (70%) or private (20.5%) hospitals, or at private office (9.5%). Hospitalization was necessary in 78.8% of the patients in university, non university public or private hospitals (38.9, 45.5 and 15.6%, respectively) with a median duration of 6.5 days. Admission was associated to old age, short delay between hemorrhage and endoscopic procedure, previous gastrointestinal bleeding, cirrhosis or cancer, bleeding from peptic ulcer or esogastric varices. Endoscopic hemostasis was performed in 21.4% of the patients, more often in university and no university public hospitals. Surgery was necessary in 4% of the patients. Death rate was 10.7%. Important geographical variations were observed concerning referral patterns. Patients' characteristics did not differ between the 4 areas. On the other hand, health care supply provided in the management of upper gastrointestinal hemorrhage was different in the four French geographical areas. CONCLUSION: a) An initial endoscopic procedure is nearly always performed in patients with an upper gastrointestinal hemorrhage in France; in 1 patient out of 10, endoscopy was performed in a private gastroenterologist office; b) hospital admission was strongly related to epidemiological and clinical criteria of severity; c) the geographical variations observed in referral patterns depend in part on health care supply; d) upper gastrointestinal haemorrhage status could be used as an indicator of the quality of health care organizations.

[Demonstration of clonal heterogeneity in adenocarcinomas on Barrett's esophagus by flow cytometric study of cellular DNA content]. / Mise en évidence d'une hétérogénéité clonale au niveau des adénocarcinomes sur endobrachyoesophage par l'étude cytofluorométrique du contenu cellulaire en ADN.

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.

[Flow cytometric analysis of cellular DNA content in Barret's esophagus. A study of 66 cases]. / Analyse du contenu cellulaire en ADN par cytométrie en flux dans les endobrachyoesophages. Etude de 66 cas.

Dysplasia is the only marker for malignant potential in Barrett's esophagus. The histologic interpretation of dysplasia is sometimes difficult, particularly when attempting to distinguish dysplastic changes from those of a regenerating and inflammatory mucosa. In order to find an objective marker to identify patients with high risk of malignant transformation, the authors evaluated 497 biopsies from 66 patients with Barrett's esophagus with flow cytometry. The aim of the study was to correlate DNA content and proliferative abnormalities with histology. All biopsies classified histologically as negative for dysplasia had a diploid DNA content. The percentage of biopsies with an aneuploid DNA content increased with the histologic grade of dysplasia: 2 percent of indefinite dysplasia, 11 percent of low grade dysplasia, 44 percent of high grade dysplasia and 78 percent of biopsy specimens with cancer biopsies were aneuploid. Mean S and G2M fractions of diploid biopsy specimens increased with the severity of histologic changes. The S and G2M fraction threshold values that could differentiate patients that were negative for dysplasia from those with high grade dysplasia or cancer were 9 percent and 6 percent, respectively. Aneuploidy or G2M fraction greater than 6 percent was the best discriminating criteria between those two distinct groups of patients. All 6 patients with high grade dysplasia or cancer had aneuploid cell populations or increased G2M fraction, whereas none of the 35 patients whose biopsies were histologically negative for dysplasia had evidence of genomic instability or increased G2M fraction. Flow cytometric abnormalities were found in 10 out of 25 patients whose biopsies were classified as indefinite for dysplasia or low grade dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)