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It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.

Introduction: Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France., Methods: An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed., Results: A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001)., Conclusions: For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.

Adenocarcinoma developed in Barrett's oesophagus is a tumour with an increasing incidence and still a poor prognosis. The only marker that can be used for surveillance remains dysplasia (intraepithelial neoplasia), especially when it is high-grade, that precedes intramucosal carcinoma. New forms of dysplasia have been described in complement to the classical intestinal type (foveolar dysplasia, basal crypt dysplasia). High-grade dysplasia and intramucosal carcinoma are diagnosed on biopsies taken during endoscopy. Standard endoscopy is now challenged by various techniques that represent recent major technical improvements (chromoendoscopy, virtual chromoendoscopy, optical frequency domain imaging, confocal laser endomicroscopy). In numerous cases, high-grade dysplasia and intramucosal carcinoma can be treated by endoscopic procedures, allowing a precise histopathological diagnosis on the resected specimen (endoscopic mucosal resection, submucosal endoscopic dissection) or destroying the neoplastic tissue. Radiofrequency ablation is currently considered as the best available technique for treatment of flat high grade dysplasia and for eradication of residual Barrett's mucosa after focal endoscopic mucosal resection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate trends in incidence and prognosis of gastric and cardia carcinomas in the area of Finistère (France) between 1984 and 2003., Methods: The Digestive Tumor Registry of Finistère recorded all new cases of gastric and cardia carcinomas from January 1, 1984 to December 31, 2003. Raw incidence data were standardized using the direct method based on the reference world population. The data and survival rates were studied in univariate and multivariate analyses., Results: Between 1984-1988 and 1999-2003 the standardized incidence of distal gastric carcinomas decreased (10.74 ± 0.39-5.68 ± 0.27/year/100 000 inhabitants, P < 0.001). There was no significant increase in the incidence of cardia carcinomas (0.83 ± 0.11-1.25 ± 0.14/year/100 000 inhabitants). The frequency of macroscopically infiltrating tumors doubled (P < 0.001) and linitis plastica increased from 9 to 16.2% (P < 0.001). Overall survival rates increased only for patients with metastatic carcinomas of both locations (P < 0.001) and with advanced tumors of distal stomach (P < 0.001) receiving therapy., Conclusion: This study showed a significant decrease over time in the incidence of distal gastric carcinomas but no significant increase in the incidence of cardia carcinomas. Despite improvement in the management of patients, prognosis remains dismal, probably because of an increased incidence of poor prognosis of histological and anatomical types.

Severe gastroesophageal reflux disease (GERD) predisposes to the development of Barrett's esophagus defined by the replacement of the squamous epithelium of the distal esophagus by a columnar epithelium. Barrett's esophagus is a precancerous condition which has a risk of malignant transformation to adenocarcinoma. Barrett's adenocarcinoma remains a relatively rare condition. Its incidence among patients followed up for Barrett's esophagus is approximately 0.5% patients per year. Besides GERD, obesity, male gender and age are the main risk factors for the development of Barrett's mucosa and esophageal adenocarcinoma. Men above 50 presenting with ancient and frequent GERD symptoms could benefit from an upper-GI endoscopy to detect Barrett's esophagus. Though still controversial, surveillance of Barrett's mucosa could allow detection of high grade dysplasia and esophageal adenocarcinoma at an early stage, enabling a curative treatment. Patients who cannot undergo surgery may be treated using endoscopic techniques such as endoscopic mucosal resection.

Background and Aim: Esophageal capsule endoscopy (ECE) is a new technology that allows noninvasive investigation of the esophagus. Our aim was to evaluate prospectively the diagnostic yield of ECE in patients with chronic reflux symptoms., Patients and Methods: Eighty-nine patients (40 men, mean age 54 yr) referred to five endoscopic centers for esophagogastroduodenoscopy (EGD) were enrolled. Patients first underwent ECE, then EGD; endoscopists who performed the EGD were blind to the ECE data that were interpreted separately by two independent readers. The Los Angeles, Prague, and Montreal classification systems were used to describe endoscopic findings., Results: Seventy-seven patients completed the study. Esophagitis and endoscopically suspected esophageal metaplasia (ESEM) were present in 24 and 10 patients, respectively. Columnar lining was histologically confirmed in seven patients (3 with specialized intestinal metaplasia and 4 with gastric metaplasia). The kappa values for interobserver agreement regarding the diagnosis of esophagitis and ESEM were 0.67 (0.49-0.85) and 0.49 (0.17-0.81), respectively. The diagnostic yields of ECE to detect esophagitis and ESEM were as follows: sensitivity 79% and 60%, specificity 94% and 100%, positive predictive value (PPV) 83% and 100%, negative predictive value (NPV) 92% and 95%, respectively., Conclusion: As a screening tool in patients with reflux symptoms, ECE has an excellent specificity and NPV for the diagnosis of esophagitis and ESEM. However, its sensitivity for the diagnosis of ESEM is not optimal. Further studies are necessary to improve the procedure, and to compare the cost-effectiveness of strategies using ECE or EGD.

Objectives: Barrett's mucosa is considered as a mosaic of three epithelial types but little is known about the topography of intestinal metaplasia in columnar lined esophagus. The aims of the study were to determine the prevalence of intestinal metaplasia within long and short segments of columnar lined esophagus and to analyze the distribution of the intestinal metaplasia within long segments of Barrett's esophagus., Patients and Methods: The study was performed on the initial endoscopy carried out among 112 patients enrolled in an endoscopic surveillance program. Seventy-two patients with columnar mucosa extending more than 3 cm into the esophagus (group I) and 40 patients with a short segment of columnar mucosa (group II) had multiple biopsies according to a standardized protocol. 1163 biopsies were analyzed on the whole: 949 biopsies in group I and 214 biopsies in group II., Results: Intestinal metaplasia was identified among 650 (68.5%) and 50 (23.4%) biopsies in groups I and II respectively (P<10-7). The proportion of biopsies with foci of intestinal metaplasia increased significantly with the length of the columnar mucosa. The diagnosis of Barrett's esophagus was confirmed in 100% of the patients in group I and in 45% of the patients in group II. In long segments of Barrett's esophagus, intestinal metaplasia was more frequently observed in the 2 upper thirds of the columnar mucosa that in the lower third (P<10-7). Detailed mapping of the distribution of epithelial types within the columnar lined esophagus identified three patterns of distribution of intestinal metaplasia within long segments of Barrett's esophagus: unifocal, multifocal and diffuse, in 5%, 56% and 39% of the patients respectively. Dysplasia was present in 15% of patients with long segments of Barrett's esophagus and 11% of patients with short segments (NS)., Conclusion: The distribution of intestinal metaplasia within columnar lined esophagus is heterogeneous and three distinct patterns can be identified: unifocal, multifocal and diffuse. Considering the risk of sampling error, the current recommendations concerning the biopsy protocols are mandatory until the validation of new techniques such as chromoendoscopy or magnifying endoscopy.

Objectives: The aims of this prospective study were to evaluate the incidence of hepatocellular carcinoma (HCC) in Finistère, an administrative district of western France, and to highlight epidemiological characteristics., Methods: From June 1st 2002 to May 31st 2003, all cases of HCC in Finistère were registered prospectively. Standardized incidence rates were calculated., Results: One hundred and six cases of HCC were registered. Standardized incidence rates were 13.8/100000 among men and 0.8/100000 among women. Among the incident cases of HCC, 52% were discovered in patients consulting for symptoms, and 28% in patients undergoing screening. The new non-invasive diagnostic criteria of HCC were used in 60% of cases. HCC was associated with cirrhosis in 89 patients (84%). Excessive alcohol intake was the main cause of cirrhosis. In all, 27 patients (25.5%) received potentially curative treatment., Conclusion: Incidence of HCC is high in Finistère. The proportion of patients given potentially curative treatment is still low, illustrating how difficult screening can be when alcoholic cirrhosis predominates in the target population.

Primary squamous cell carcinoma of the pancreas is a rare tumor. We report a case of a 49 years old patient with a metastatic squamous cell carcinoma of the pancreas. Histological diagnosis was established by echoguided biopsy of the liver. Due to that, we cannot be sure that this tumor was not adenosquamous with a metastatic component from only the squamous part of the lesion. Two types of chemotherapy have been performed. The first one was radiochemotherapy with an association of 5FU and cisplatinum. Gemcitabin was the second one. An objective response was obtained with gemcitabin and the patient's health improved. To our knowledge, this has never had been reported beforehand. However the prognosis of this cancer remains poor. Overall survival was 8 months.

Introduction: Being an easy-to-use (eight items) quality of life questionnaire specific to GERD, the Reflux-Qual Short form (RQS) was developed for use in everyday practice. The purpose of this study was to assess the psychometric properties of the RQS., Methods and Materials: The reliability of the RQS was measured by the Cronbach's alpha coefficient and its clinical validity by comparing the RQS score for increasing clinical severity groups. The RQS discriminative power was compared with that of the SF12. Sensitivity to change over time was measured by calculating effect-sizes., Results: The reliability and validity of the questionnaire were assessed on a sample of 1195 patients. Its psychometric properties were very satisfactory: Cronbach alpha = 0.84; RQS score significantly reduced for the worst-affected patients; the discriminative power was up to 5 times higher when compared with the SF-12. Sensitivity to change over time, evaluated with 362 patients, showed highly significant differences between groups with different levels of clinical progression (P = 0.0001)., Conclusion: The RQS is a quality of life measurement instrument specific to GERD which is short, reliable, valid, and sensitive to within and between-subject differences.

Objectives: The aims of this study were to evaluate trends in incidence, clinical characteristics, treatment regimen and prognosis of gastric carcinoma in the area of Finistere (France) during a 12-year period., Methods: Between 1984 and 1995, the Finistere Registry of GastroIntestinal Tract Tumors listed 2 139 patients with gastric carcinoma in a population of 838 627 inhabitants. Curative resection and operative mortality were analyzed by logistic regression. Prognostic factors were determined using the Kaplan-Meier method and the Cox model., Results: When comparing the second period (1990-1995) to the first period (1984-1989) we observed: a) a decrease of standardized incidence (13.2 vs. 15.6/100 000 inhabitants/year in males and 5.4 vs. 7.0/100 000 inhabitants/year in females); b) a significant increase of linitis plastica (21.4% vs. 10.9%) and infiltrative tumors (53.1 vs. 31.2%) (P<0.0001); c) no variation in tumor stage at diagnosis; d) a significant increase in curative resection (65.7% vs. 45.0%; P<0.0001); e) no variation in operative mortality; f) the absence of improvement of survival rate; the latter was 29% at 2 years, 19% at 5 years and 11% at 10 years during the second period. Multivariate analysis showed that the main prognostic factors of gastric carcinoma were age, tumor stage and the type of surgical procedure., Conclusion: This study showed a decrease in the incidence of gastric carcinoma over time and an increase of linitis plasticia and infiltrative forms. Despite improvement in management of patients, the global prognosis of gastric carcinoma did not improve significantly over a 12-year period of observation.

Unlabelled: Liver steatosis is a common finding in patients infected with hepatitis C virus (HCV). Host and viral factors have been associated with steatosis, but their relative contributions have not been clearly addressed. It has been suggested that steatosis plays a role in the progression of liver fibrosis., Aims: To assess: a) factors associated with steatosis in patients infected with hepatitis C virus; b) their impact on liver fibrosis., Patients and Methods: Three hundred and fourteen untreated patients were included. Lifetime alcohol consumption was estimated. Liver fibrosis, inflammation and necrosis were assessed using the METAVIR score. Body mass index (BMI) was determined. The scoring system for steatosis was as follows: 0, no steatosis; 1, less than 10%; 2, 10% to 30%; 3, 30% to 70%; 4, more than 70% of hepatocytes affected., Results: In univariate analysis, steatosis was associated with elevated BMI (P=0.001), excessive alcohol intake (P=0.005), genotype 3 (P<0.001) and moderate to severe histological activity (P=0.01). Multivariate analysis showed that steatosis correlated with two independent factors: genotype 3a (OR=60.7; 95% CI: 7.6-483.4) (P<0.001) and BMI (OR=4.86; 95% CI: 1.8-13.15) (P=0.002). In univariate analysis, severe fibrosis (F2-F3-F4) was associated with older age (P<10(-5)), male gender (P=0.001), disease duration (P<0.006), BMI (P<10(-4)), alcohol intake (P<10(-6)), severity of histological activity (P<10(-5)) and steatosis (P<10(-6)). In multivariate analysis, three independent factors were associated with severe fibrosis: disease duration > 10 years (OR=3.17; 95% CI: 0.65-15.4) (P=0.015), presence of steatosis (OR=3.17; 95% CI: 1-9.99) (P<0.049) and genotype 3a (OR=5.56; 95% CI: 1.4-22.1) (P=0.015)., Conclusion: In patients with chronic hepatitis C, steatosis is significantly associated with genotype 3 infection and high BMI. Steatosis is an independent risk factor associated with severe fibrosis. These results have major implications for the management of patients with chronic hepatitis C.

In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly, 'gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably 'loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one 'mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.

Loss of heterozygosity (LOH) on chromosome 9 and p16 (MTS1/CDKN2) gene mutations have been reported in various human cancers. The present study aimed to determine the prevalence of LOH in 100 oesophageal squamous cell carcinomas (OSCCs) by typing microsatellite loci and mutations of the p16 gene. The methods used included denaturing gradient gel electrophoresis (DGGE) and DNA sequencing of exon 2. LOH was found in 14.7% of the OSCC cases. Six gene alterations were identified in exon 2. They consisted of three deletions and the same polymorphism in three samples. The relatively low rate of p16 mutation compared with the frequency of LOH suggests the possible involvement of another tumour suppressor gene located on chromosome 9 in oesophageal carcinogenesis.

The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.

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.

Mutations of the tumor suppressor gene TP53 have been detected in tumor tissues of a large variety of human malignancies and contribute to the development, progression and probably the prognosis of the disease. The pattern of somatic mutations in the TP53 gene in human tumors most often consists of a point mutation in one allele accompanied by loss or rearrangement of the second allele. Esophageal cancer is one of the most commonly mutated cancer, p53 mutations having an incidence greater than 80% in squamous cell carcinoma. The profile of distribution of these mutations in the TP53 gene is of interest to establish correlation between the exposure to carcinogens responsible for DNA mutations. The other form of esophageal cancer, Barrett's esophageal is a good model to study the role of TP53 in mammalian tumorigenesis.

Objectives: The aim of the study was to determine the incidence and the main clinical data of inflammatory bowel disease in Brittany., Methods: According to EPIMAD registry's methodology, private and public gastroenterologists (n = 139) of Brittany (2836418 inhabitants) referred all patients consulting for the first time, in 1994 and 1995 with clinical symptoms compatible with inflammatory bowel disease. An interviewer practitioner completed at the gastroenterologist's consulting room a standard questionnaire for each patient. Each case was reviewed separately by four experts to assign a diagnosis of definite, probable, possible Crohn's disease, ulcerative colitis, unclassifiable chronic colitis, or acute colitis (onset of symptoms < 6 weeks)., Results: 657 cases were recorded: 205 Crohn's disease (31%), 165 ulcerative colitis (25%) including 75 ulcerative proctitis (46%), 42 unclassifiable chronic colitis (7%), 245 acute colitis (37%). The crude mean annual incidence (per 10(5) inhabitants) based on definite and probable cases only was 2.8 for Crohn's disease and 2.9 for ulcerative colitis. The female/male ratio was 0.9 for Crohn's disease and 0.5 for ulcerative colitis. The median age at time of diagnosis was 27 for Crohn's disease and 36 for ulcerative colitis. The median time between onset of symptoms and diagnosis was equal to 3 months for Crohn's disease and ulcerative colitis., Conclusion: In Brittany the observed incidence of ulcerative colitis is similar to that of Crohn's disease and close to that observed in northern France. The incidence of Crohn's disease is lower. However, the real incidence of inflammatory bowel disease is currently underestimated due to the large number of acute colitis requiring a follow up and the cases of Crohn's disease classified as possible not taken into account.

Previous studies have suggested that patients with Barrett's oesophagus may be at increased risk of colorectal neoplasia, though the association is disputed. In a multicentre prospective study we compared the prevalence of colorectal adenomas in patients with Barrett's oesophagus and controls. Barrett's oesophagus patients (n = 104) had histological confirmation of columnar epithelium extending more than 3 cm above the gastro-oesophageal junction. The 537 controls were patients with symptoms suggesting irritable bowel syndrome. No participant had a personal history of colonic neoplasm. Each patient underwent colonoscopy. Histologically proven adenomas were found in 26 Barrett's patients (25%) and 75 controls (14%). Three colorectal cancers were discovered in each group. The prevalence of adenomas was greater in the Barrett's oesophagus group than in the control group (p < 0.01) but the relation became non-significant after adjustment for age and sex and control for other known risk factors by a logistic regression model (odds ratio 1.4 [0.7-2.7]). The relative risk of adenoma was significantly higher in patients older than 59 than in younger patients (2.2 [1.3-3.5]) and in men than in women (3.4 [2.0-5.7]). Other factors contributing significantly to the risk of adenoma were a family history of colorectal cancer (2.3 [1.1-4.8]), rectal bleeding (2.1 [1.1-3.9]), previous colonic investigation (0.3 [0.1-0.7]), and complete as opposed to partial colonoscopy (6.4 [0.8-48.3]). We conclude that Barrett's oesophagus is not an independent risk factor for colorectal neoplasia and, therefore, is not, in itself an indication for colorectal screening.

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.

Objectives and Methods: In Barrett's oesophagus, the risk of malignancy is evaluated histologically with the presence of dysplasia. The abnormal expression of p53 protein could represent a useful new marker. The aim of this study was evaluate the abnormal expression of p53 protein in a series of 52 oesophagectomy specimens with Barrett's oesophagus, either non-dysplastic (n = 3), dysplastic (n = 8), or malignant (n = 41). The immunohistochemical study was made on deparaffinized sections with the monoclonal anti-p53 antibody DO7., Results: The 3 non-dysplastic cases were p53 negative; 1 case of low-grade dysplasia in 5 was positive, as were the 3 cases of high grade dysplasia and 33 of 41 cancers (80%), including 13 superficial cancers in 14 (93%) and 20 invasive cancers in 27 (74%). A common feature was the presence of rare p53 positive crypts in low grade dysplastic areas and non-dysplastic specialized mucosa that surrounded high grade dysplasia and cancers., Conclusions: Our results confirm the high frequency of the abnormal expression of p53 protein in cancer developed in Barrett's oesophagus. This expression is a consequence of alterations of the TP53 gene, and has an important role in the carcinogenesis of Barrett's mucosa; it is likely to represent an early event. Prospective studies are needed to evaluate its interest in the surveillance of patients with Barrett's oesophagus.

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.

Esophageal squamous cell carcinoma is a form of cancer occurring most commonly in males, particularly those living in some areas of Asia, Africa, and western Europe. In some of these tumors, a sequence alteration has been identified in the coding region of the TP53 gene which is known to inactivate the tumor suppressor function of its product. Using a GC clamp (i.e., a GC rich domain) denaturing gradient gel electrophoresis assay we have been able to identify sequence modifications in 27 of the 32 tumor samples analyzed (84%). Most of the mutations occur in exon 6, a region of the gene which has not previously been reported as being a hot spot for the mutations of other cancers. Twelve of the mutations reported here have not been described in other types of tumors and these consist mostly of frameshift or splice mutations. The distribution of mutations [transitions (45%), transversions (34%), and frameshift (21%)] suggests that the etiological contribution of genotoxic factors might be complex and might associate different exogenous and endogenous mutagen exposures.

Endoscopic ultrasound (endosonography) is useful in the preoperative staging of oesophageal tumours. It may also have a role in evaluation and surveillance of patients with inoperable carcinomas. Thirty four patients with inoperable oesophageal cancer were investigated by endosonography and computed tomography before medical treatment. In 10 patients receiving combined chemotherapy and radiotherapy, the endoscopic lesions resolved and biopsy specimens were negative. When endosonography suggested the persistence of tumour infiltration in these patients, a local recurrence or distant metastases appeared within a few months. In contrast, when no infiltration was detected, no tumoral recurrence or progression was observed within eight months. These results suggest that endosonography is better than endoscopic biopsy specimens and computed tomography in assessing the response of oesophageal carcinoma to non-surgical treatment.

The authors report two cases of colonic intussusception in the adult protruding from the anus--or colo-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon.

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.

To better understand the mechanisms of esophageal carcinogenesis, abnormalities in DNA content of esophageal squamous cell carcinomas were studied. Cellular DNA content was determined by flow cytometric study of 70 endoscopic biopsy specimens obtained from 26 patients with esophageal squamous carcinoma. High-quality histograms were obtained for 23 patients. Twenty-one patients had at least one aneuploid population in their tumor. In 7 patients, multiple aneuploid peaks were detected. Specimens from 2 patients were diploid. The interpretation of the DNA histograms was difficult in 3 patients; an aneuploid population of cells was probable in 2 of them. A statistically significant relationship was found between the degree of differentiation and DNA content abnormalities in the regions of the tumors that could be evaluated by endoscopic biopsies: well-differentiated carcinomas had diploid or small aneuploid populations containing less than 15% of the cells, whereas DNA histograms of moderately or poorly differentiated carcinomas were characterized by large aneuploid peaks representing 25%-90% of the cells and a higher proliferative fraction. No relationship was found between the size or the stage of the tumor and the DNA content detected in endoscopic biopsy samples. The frequency and the multiplicity of abnormal clones in esophageal squamous carcinomas indicates that this cancer, like esophageal adenocarcinoma, develops an association with an acquired genomic instability that produces abnormal clones of cells, according to the multistep model of neoplastic progression.

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)

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.