A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

TP53 gene mutation profile in esophageal squamous cell carcinomas.

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.

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.

[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.

[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.

[Attempt at preventive treatment of esophagitis caused by intubation during intensive care]. / Tentative de traitement préventif des oesophagites sur sonde en réanimation.

A randomized prospective trial was designed to evaluate the preventive treatment of esophagitis in 31 intensive care patients who had a nasogastric feeding tube for at least 10 days. Fourteen patients (group B) received no preventive treatment while 17 patients (group A) received 300 mg of cimetidine every 6 h intravenously and 11 g of colloidal aluminium phosphate every 4 h per os. All patients were fed a standard diet through their nasogastric tube at a constant rate of 30 Kcal/kg/day. Endoscopic controls at day 1 and 10 showed that the number of initial and final esophagitis was not different in groups B and A: 7 and 8 at day 1, 11 and 10 at day 10, respectively. The inefficiency of this preventive treatment suggested that acid gastroesophageal reflux is not a major factor in the occurrence of nasogastric feeding tube-induced esophagitis. However as esophagitis is associated with a more severe Knaus index and a greater number of gastric stress ulcer risk factors, it is suggested that decreased defense of the mucosa may be a key factor in the occurrence of this type of esophagitis.

[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.

[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)

[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.

[Incidence of inflammatory bowel diseases in Bretagne (1994-1995). ABERMAD. Association Bertonne d'Etude et de Recherche des Maladies de l'Appareil Digesif]. / Incidence des maladies inflammatoires du tube digestif en Bretagne (1994-1995). ABERMAD. Association Bertonne d'Etude et de Recherche des Maladies de l'Appareil Digesif.

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.

[Overexpression of protein p53 and Barrett esophagus. A frequent and early event in the course of carcinogenesis]. / Surexpression de la protéine p53 et endobrachyoesophage. Un événement fréquent et précoce au cours de la carcinogenèse.

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.

[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.

[Primary colonic intussusception protruding from the anus in adults. Two cases]. / Invagination colique primitive de l'adulte, procidente à l'anus. Deux observations.

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.

[Barrett esophagus. Current situation of the risk and surveillance policy]. / Endobrachyoesophage. Situation actuelle du risque et politique de surveillance.

Barrett's oesophagus is a condition in which a metaplastic columnar mucosa replaces the normal squamous epithelium of the lower oesophagus. Barrett's oesophagus develops as a complication of gastro-oesophageal reflux and predisposes to the development of oesophageal adenocarcinoma. Most adenocarcinomas arising in Barrett's mucosa are far advanced at the time of diagnosis, and prognosis is consequently poor. Regular endoscopic surveillance of patients with Barrett's oesophagus is recommended to detect the oesophageal malignancy in an early presymptomatic stage. The concept of screening is based on the notion that regular surveillance can reduce the mortality, but there is yet little evidence that this is the case in Barrett's oesophagus. Screening is generally carried out by regular endoscopy with multiple biopsies in an attempt to detect dysplasia. Unfortunately, dysplasia is not an ideal biomarker of malignant potential in Barrett's oesophagus. There is an interest in research into more sensitive and effective predictors of heightened risk for development of malignancy. DNA content flow cytometry and p53 protein expression might be useful in managing the cancer risk in Barrett's patients. However these new techniques need further evaluation before they can be applied to routine clinical investigation.

[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.