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)

[Upper gastrointestinal bleeding in patients treated by low-dose aspirin]. / Hémorragies digestives hautes et aspirine à faible dose.

AIM OF THE STUDY: To estimate the number of people treated by low-dose aspirin (<330 mg daily) in France and to evaluate the risk of upper gastrointestinal bleeding associated with low-dose aspirin treatment. SUBJECTS AND METHODS: One thousand six hundred and two patients with upper gastrointestinal bleeding were included between January and June 1996 in 4 French areas. Data about patients characteristics, drugs recently used, and bleeding lesions were prospectively collected. Five hundred seventy five cases were matched for sex, age and area with control people without previous upper gastrointestinal bleeding. Low-dose aspirin intake in the population was estimated from the control group. Aspirin intake in the previous 7 days in cases and in controls was compared by logistic regression, adjusted for other gastrotoxic drugs intake. RESULTS: Low-dose aspirin is taken by about 1.2 millions adults in France. In 1 602 patients, gastrointestinal bleeding was related to a peptic ulcer in 34%. Aspirin was associated with higher risk of upper gastrointestinal bleeding: OR=1.68 (1.03-2.74) with low-dose, and OR 1.42 (0.91-2.21) with higher doses. CONCLUSION: About 2.8% of the population is exposed to low-dose aspirin in France. This treatment seems to be associated with a high risk of upper gastrointestinal bleeding.

[Therapeutic management and survival of gastric adenocarcinoma in the province of Finistère between 1984 and 1989]. / Prise en charge thérapeutique et survie de l'adénocarcinome gastrique dans le département du Finistère entre 1984 et 1989.

OBJECTIVES: The aim of this study was to analyze the evolution of treatment regimens and survival rates of stomach adenocarcinoma recorded in the Finistère cancer registry from 1984 to 1989. METHODS: In a population of 838,627 inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated by the actuarial method, and compared using the logrank test and the Cox model. RESULTS: Surgical resection was the main treatment for 661 patients (57%). The frequency of curative resection increased from 25% between 1984 and 1986 to 35% after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only symptomatic treatment. The survival rates of all patients were 43% at 1 year and 20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with cancer managed surgically, the factors associated with a better prognosis were young age, long duration of symptoms before diagnosis, ulcerated macroscopic aspect, limited tumour extension and curative surgical resection. In other patients, 2 factors were associated a with better prognosis: the absence of metastases and an endoscopic palliative treatment. CONCLUSIONS: Surgical resection is the main treatment of gastric adenocarcinoma. Although the frequency of surgery increased, the prognosis of gastric adenocarcinoma did not improve within this 6-year period.

[Treatment of and survival after epidermoid cancer of the esophagus in the department of Finistère between 1984 and 1988 (716 cases)]. / Traitement et survie du cancer épidermoïde de l'oesophage dans le département du Finistère entre 1984 et 1988 (716 cas).

The incidence of esophageal cancer in the French county of Finistère is among the highest in France (26.7/10(5) for males). The authors analyzed the survival rates for squamous cell carcinomas from data of the Finistère tumor registry in order to describe different prognostic groups of patients using the multivariate Cox model. From 1984 to 1988, 716 patients with esophageal squamous cell carcinomas were registered in an overall population of 828,000 residents: 675 males and 41 females. Survival was calculated using the actuarial method. Six hundred and seventy five patients died before the point date (31 Dec 1989). Only one patient was lost to follow-up. The actuarial survival rates of all patients were 89 +/- 1% at 3 months, 68 +/- 2% at 6 months, 37 +/- 2% at one year, 12 +/- 1% at 3 years and 6 +/- 1% at 5 years; median survival was 9.1 +/- 0.4 months. Survival was significantly related to cancer size, tumor extension and surgical contraindications. In the Cox model, age, cancer size, surgical contraindications, year of diagnosis were independent prognostic predictors. There was a significant increase in survival rates after 1986: median survival was 8.1 +/- 0.4 months between 1984 and 1986 and 10.1 +/- 0.5 months between 1987 and 1988. Patients treated by curative resection had higher actuarial survival rates (median survival 22.5 +/- 4.1 months) than patients who underwent palliative resection (median survival 11.3 +/- 1.2 months). In patients with cancer managed surgically, the prognostic predictors were tumor size, curative vs palliative surgical resection and association with chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gastroduodenal metastases: an unusual manifestation of lung cancer. Study of two cases and review ot the literature]. / Métastases gastroduodénales: un mode de révélation exceptionnel du cancer du poumon. Etude de deux cas et revue de la littérature.

INTRODUCTION: Diagnosis of gastroduodenal metastases is rare. Primary tumors are essentially melanomas and breast cancer, and exceptionally lung cancer. EXEGESIS: We report two patients who have a diagnosis of gastroduodenal metastases as initial manifestation of lung cancer. In one case, the patient died 3 weeks after the diagnosis. In the other case, chemotherapy was performed and complete response was obtained for the gastric metastasis. After a few months, node recurrence was diagnosed and the patient died 8 months after the diagnosis. CONCLUSION: We review the endoscopic and non-endoscopic literature and discuss the different histological types and therapeutic strategies concerning these unusual manifestations of lung cancer.

[Ivor Lewis' operation for epidermoid cancer of the esophagus. Immediate and late results. Apropos of 168 cases]. / Intervention d'Ivor Lewis pour cancer épidermoïde de l'oesophage. Résultats immédiats et tardifs. A propos de 168 cas.

168 Ivor Lewis operations for squamous carcinoma of the lower esophagus are reviewed. 155 men and 13 women with a mean age of 59 years were operated on. 46 tumors were stage I and II, and 122 were stage III. Operations were considered to be curative for 120 patients and only palliative for 48. An esophagectomy associated with lymphadenectomy was performed through laparotomy and right thoracotomy. Feeding jejunostomy and pyloroplasty were routine. EEA or ILS 25 staplers were used to perform esophagogastric anastomosis and the gastroplasty tube was fashioned by TA 90 stapler. In every case an extended esophagectomy was performed with anastomosis between 3 ans 7 cm below the pharyngo-esophageal junction. Postoperative mortality was 4.7%. There were 10 leaks (6%) and 28 pulmonary complications. Median actuarial survival is 17 months. Actuarial survival at 2 years is significantly greater for stages I and II (68.4%) than for stage III (23.2%) (p < 0.01). Ivor Lewis esophagectomy is a reliable procedure to treat squamous carcinoma of the lower two thirds of the esophagus ensuring a good quality of life.

[Hemorrhaging eso-gastro-duodenal ulcers: epidemiology and management. A multicenter prospective study]. / Les ulcères oeso-gastro-duodénaux hémorragiques: épidémiologie et prise en charge. Etude prospective multicentrique.

UNLABELLED: The aim of this study was to estimate the incidence, and to describe the characteristics and medical care in patients with bleeding upper gastrointestinal ulcers in the general population. PATIENTS AND METHODS: A study was performed over six months in 1996 in 4 French geographical areas: Finistère, Gironde, Seine-Maritime, and the Somme (3 million people minimum 18 years). All public or private hospitals, and specialist gastroenterologists in private practice participated in the study, based on a standardized questionnaire. RESULTS: Over 6 months 793 patients with bleeding ulcers were identified, corresponding to 27 per 100,000 inh./year or 24,000 cases in France. Most patients were men (60%) and 40.1% were 75 years and older. The ulcer was oesophageal (6%), gastric (47%), or duodenal (69%). In 406 patients (51.2%) a chronic disease was present (cancer, cirrhosis, circulatory, respiratory or cardiac disease). In 237 cases (29.9%) the ulcer occurred in patients, 453 patients (57.1%) were admitted and 103 patients (13%) were managed as outpatients. Gastrotoxic drugs were taken by 349 patients (44%): non steroidal anti-inflammatory drugs (18.7%), aspirin (21.2%, including 2/3 with doses under 330 mg/day), corticosteroids (7.8%) and 24.3% had anticoagulant therapy. Patients were managed in university hospitals (39.3%), other public or non profit hospitals (44.2%) or private hospital (16.5%) with geographical differences between the 4 areas. Therapeutic endoscopy was performed in 16.9% and a surgical procedure was performed in 5.9%. The mortality rate (outpatients excluded) was 13.5% (n = 93), but only 2% (n = 16) of death were associated with a bleeding ulcer: mortality was higher in inpatients (24.1%) than in out patients (8.1%). A chronic disease was also associated with higher mortality (17.9% versus 8.1%). CONCLUSION: Bleeding ulcers are frequent and severe, especially in inpatients or associated with chronic conditions. A gastrotoxic drug used is found in about fifty percent of the cases.

Rioprostil in the short-term treatment of duodenal ulcer: a multicentre double-blind trial vs. cimetidine.

The efficacy and safety of the new prostaglandin E1 (PGE1) synthetic analogue, rioprostil, 300 micrograms b.d. and cimetidine, 400 mg b.d., on duodenal ulcer healing are compared in an international, multicentre, double-blind study. A total of 257 patients have entered the study; 243 are considered eligible for efficacy analysis and 207 for safety analysis. After 4 and 6 weeks of treatment, the endoscopic healing rates do not significantly differ between the two groups, being 55% and 83% respectively with rioprostil vs. 60% and 78% respectively with cimetidine. The major adverse effect attributable to rioprostil is diarrhoea, which was documented in 11% of patients compared with 1% of patients taking cimetidine. However, central nervous system complaints are twice as frequent in the cimetidine group. Monitoring of clinical laboratory tests show no significant abnormalities when compared with the baseline values during the administration of either drug. This study documents that rioprostil, at the dosage of 300 micrograms b.d., is as effective and safe as cimetidine in the short-term therapy of duodenal ulcer.

[Palliative and curative endoscopic treatment of cancer of the esophagus]. / Traitements endoscopiques palliatifs et curatifs des cancers de l'oesophage.

The most common indication for endoscopic treatment of oesophageal cancers is palliative, owing to their late diagnosis and high rate of inoperability. The aim is to maintain oesophageal permeability. Technical progress in tumoral reduction (ethanol necrosing injections, plain or argon electrocoagulation, laser), which can be combined to radiochemotherapy, has limited the use of other methods: dilatations have short-lived efficacy; inoperable oesotracheal fistula is the main indication for endoscopically inserted prosthesis. Curative endoscopy is indicated for localised and superficial tumours in patients who are judged unfit for surgery. Mucosectomy, photodynamic therapy, intracavitary brachytherapy or local injections of anticancer drugs can then be employed either alone or, more commonly, combined with one another and with general radiochemotherapy.

[Flow cytometry and digestive pathologies]. / Cytométrie en flux et pathologies digestives.

Flow cytometry provides rapid evaluation of nuclear DNA content and cell cycle analysis. The major applications of flow cytometry in gastroenterology are the evaluation of DNA content and proliferative indices as prognostic indicators of gastrointestinal malignancies, and the screening of premalignant conditions of the digestive tract.