P. Bocus

The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies

BACKGROUND Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K-ras gene is present in over 75% of pancreatic adenocarcinomas (PADC). OBJECTIVE To assess the accuracy of K-ras gene mutation analysis for diagnosing PADC. DESIGN We systematically searched the electronic databases for relevant studies published. Data from selected studies underwent meta-analysis by use of a bivariate model providing a pooled value for sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve. SETTING Meta-analysis of 8 prospective studies. PATIENTS Total of 931 patients undergoing EUS-FNA for diagnosis of pancreatic solid masses. INTERVENTION K-ras mutation analysis. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy of K-ras mutation analysis and of combined diagnostic strategy by using EUS-FNA and K-ras mutation analysis in the diagnosis of PADC. RESULTS The pooled sensitivity of EUS-FNA for the differential diagnosis of PADC was 80.6%, and the specificity was 97%. Estimated sensitivity and specificity were 76.8% and 93.3% for K-ras gene analysis, respectively, and 88.7% and 92% for combined EUS-FNA plus K-ras mutation analysis. Overall, K-ras mutation testing applied to cases that were inconclusive by EUS-FNA reduced the false-negative rate by 55.6%, with a false-positive rate of 10.7%. Not repeating EUS-FNA in cases in which mutation testing of the K-ras gene is inconclusive would reduce the repeat-biopsy rate from 12.5% to 6.8%. LIMITATIONS Small number of studies and between-study heterogeneity. CONCLUSION K-ras mutation analysis can be useful in the diagnostic work-up of pancreatic masses, in particular when tissue obtained by EUS-FNA is insufficient, and the diagnosis inconclusive.

Endosonography in gastric lymphoma and large gastric folds.

To establish a correct preoperative differential diagnosis between gastric lymphoma and cancer is essential but can be difficult as endoscopic biopsies can sometimes provide a low diagnostic yield. By EUS, infiltrative carcinoma tends to show a vertical growth in the gastric wall, while lymphoma tends to show mainly a horizontal extension. EUS provides an accurate staging of gastric lymphoma, showing the exact level of infiltration and the presence of perigastric lymph nodes, thus the physician can obtain an accurate prognosis for each patient and select the best form of treatment accordingly. The response to chemoradiotherapy can also be investigated very accurately by EUS. Large gastric folds are seen in a great number of benign and malignant conditions. Diagnosis represents a clinical challenge because etiology may be extremely varied and standard biopsies are often inconclusive. Different diseases show different levels of infiltration of the gastric wall, thus a characteristic echo-pattern helps for the differential diagnosis. Endosonography, used always in combination with biopsy, allows to rule out malignancies and to select the most appropriate treatment for each patient (medical or surgical).

Programmed cell death 4 (PDCD4) expression during multistep Barrett's carcinogenesis

Aim To test the contribution of programmed cell death 4 (PDCD4) tumour suppressor gene in Barretts carcinogenesis. Methods PDCD4 immunohistochemical expression was assessed in 88 biopsy samples obtained from histologically proven long-segment Barretts mucosa (BM; 25 non-intestinal columnar metaplasia, 25 intestinal metaplasia (IM), 16 low-grade intraepithelial neoplasia (LG-IEN), 12 high-grade IEN (HG-IEN) and 10 Barretts adenocarcinoma (BAc)). As controls, 25 additional samples of native oesophageal mucosa (N) were obtained from patients with dyspepsia. To further support the data, the expression levels of miR-21, an important PDCD4 expression regulator, in 14 N, 5 HG-IEN and 11 BAc samples were determined by quantitative real-time PCR analysis. Results PDCD4 immunostaining decreased progressively and significantly with the progression of the phenotypic changes occurring during Barretts carcinogenesis (p<0.001). Normal basal squamous epithelial layers featured strong PDCD4 nuclear immunoreaction (mostly coexisting with weak–moderate cytoplasmic staining). Non-intestinal columnar metaplasia and intestinal metaplasia preserved a strong nuclear immunostaining; conversely, a significant decrease in PDCD4 nuclear expression was seen in dysplastic (LG-IEN and HG-IEN) and neoplastic lesions. Weak–moderate cytoplasmic immunostaining was evident in cases of LG-IEN, while HG-IEN and BAc samples showed weak cytoplasmic or no protein expression. As expected, miR-21 expression was significantly upregulated in HG-IEN and BAc samples, consistently with PDCD4 dysregulation. Conclusions These data support a significant role for PDCD4 downregulation in the progression of BM to BAc, and confirm miR-21 as a negative regulator of PDCD4 in vivo. Further efforts are needed to validate PDCD4 as a potential prognostic marker in patients with Barretts oesophagus.

Weekend therapy for the treatment of Helicobacter pylori infection.

Objective:The aim of the present study was to evaluate the efficacy and the safety of a short-term regimen (weekend therapy) in the cure of Helicobacter pylori infection and to analyze the factors that may influence the success of the treatment.Methods:Seventy-one patients with gastric colonization by a tinidazole sensitive H. pylori strain (34 duodenal ulcer and 37 nonulcer dyspepsia) received omeprazole 40 mg o.m. for 7 days (from Monday to Sunday) and bismuth 240 mg q.i.d. + amoxicillin 1000 mg/q.i.d. + tinidazole 500 mg q.i.d. for only 2 days (Saturday and Sunday). Endoscopy, histology, culture, urease test, and susceptibility studies were done at entry and 30 days after treatment.Results:Successful eradication was obtained in 84% of patients. The percentage of eradication was higher in duodenal ulcer patients (94%) than in those with nonulcer dyspepsia (74%; p < 0.05), and in patients who received the treatment during hot weather (94%) than in those who received the treatment during cold weather (74%; p < 0.05). Side-effects were induced by the treatment in 17% of patients, and these were all not severe, self-limiting, short-lasting, and did not require specific treatment.Conclusions:These data suggested that weekend therapy with high doses of drugs represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection, particularly in patients with duodenal ulcer. Furthermore, they also confirm the relevant role that short-term treatments may play in the therapeutic approach to H. pylori infection, and highlight some important aspects influencing short-term schedules.

Interobserver agreement in contrast harmonic endoscopic ultrasound

Background and Aim:  Contrast harmonic endoscopic ultrasound (CH‐EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the interobserver agreement (IA) in CH‐EUS.

Original ContributionsWeekend therapy for the treatment of Helicobacter pylori infection

Objectives: The aim of the present study was to evaluate the efficacy and the safety of a short-term regimen (weekend therapy) in the cure of Helicobacter pylori infection and to analyze the factors that may influence the success of the treatment. Methods: Seventy-one patients with gastric colonization by a tinidazole sensitive H. pylori strain (34 duodenal ulcer and 37 nonulcer dyspepsia) received omeprazole 40 mg o.m. for 7 days (from Monday to Sunday) and bismuth 240 mg q.i.d. + amoxicillin 1000 mg/q.i.d. + tinidazole 500 mg q.i.d. for only 2 days (Saturday and Sunday). Endoscopy, histology, culture, urease test, and susceptibility studies were done at entry and 30 days after treatment. Results: Successful eradication was obtained in 84% of patients. The percentage of eradication was higher in duodenal ulcer patients (94%) than in those with nonulcer dyspepsia (74%; p < 0.05), and in patients who received the treatment during hot weather (94%) than in those who received the treatment during cold weather (74%; p < 0.05). Side-effects were induced by the treatment in 17% of patients, and these were all not severe, self-limiting, short-lasting, and did not require specific treatment. Conclusions: These data suggested that weekend therapy with high doses of drugs represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection, particularly in patients with duodenal ulcer. Furthermore, they also confirm the relevant role that short-term treatments may play in the therapeutic approach to H. pylori infection, and highlight some important aspects influencing short-term schedules.

A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

Cancer of the Esophagus - Endoscopic Ultrasound: Selection for Cure

Several treatment options are available to treat esophageal cancer. Ideally, treatment should be individualized, based on the projected treatment outcome for that individual. Accurate staging of the extent of the disease at the time of diagnosis offers the most rational attempt at stratifying patients into categories that can be used to affect treatment choices. Endoscopic ultrasonography (EUS) is the most accurate nonoperative technique for determining the depth of tumour infiltration and thus is accurate in predicting which patients will be able to undergo complete resection. EUS is also being used for tumour staging in order to guide treatment decisions in patients with esophageal cancer.

Les aspects endoscopiques de l’hypertension portale: diagnostic et classification

RésuméQuand s’instaure un état d’hypertension portale, des circulations collatérales entre le système porte et le système cave se forment ou s’ouvrent.Du point de vue clinique, les plus importantes sont celles qui impliquent le secteur gastro-intestinal, parce qu’elles peuvent provoquer la dilatation du plexus sous-muqueux avec formation de varices endoluminales.Les varices peuvent se trouver sur tous secteurs du tractus gastro-intestinal (oesophage, estomac, duodénum, iléon, côlon, rectum), mais les varices gastro-oesophagiennes s’observent plus fréquemment et en cas de rupture, elles peuvent provoquer de graves hémorragies. L’hémorragie de varices oesophagiennes représente encore aujourd’hui une des plus graves complications de la cirrhose hépatique et un défi toujour renouvelé pour l’endoscopiste.Malgré l’introduction de nouveaux moyens diagnostiques et de nouvelles thérapies, la mortalité au premier épisode de saignement reste encore très ⫑evée (30%–40%).Ceci est lié non seulement à l’entité de l’hémorragie et à la vitesse de son contrôle mais également au stade d’insuffisance hépatique et à l’apparition de complications cardio-pulmonaire, rénales, infectieuses et surtout hémorragiques.L’examen endoscopique, s’il est conduit de manière correcte, représente la meilleure technique pour le diagnostic, la classification et la thérapie aussi bien en première intention qu’en urgence.SummaryDuring portal hypertension occurs the formation and/or opening of collateral circulations between the portal and caval systems.One of the most significant clinical consequences is the formation of endoluminal varices at the intestinal level. There is also congestion of the mucosa, termed portal congestive gastropathy or portal congestive colonopathy, depending on the area affected.Varices could be present in the entire gastro-intestinal tract (esophagus, stomach, duodenum, ileum, colon, rectum). However the most frequently observed are the esophageal varices and in case of rupture they cause severe haemorrhage.Bleeding from esophageal varices is one of the most important complications of liver cirrhosis and represent a critical moment for the endoscopist.Although the use of modern diagnostic and therapeutic technique, mortality during the first episode of bleeding still remains very high (30–40%).This is related not only to the entity of the haemorrhagic fact and the endoscopic ability to control it, but also to the degree of the liver disease, cardiopulmonary, kidney, infective and haemorrhagic complications.Endoscopic examination, if correctly performed, represents the best technique for the diagnosis, the classification and the therapeutic approach both in election and emergency.

OC.01.7: ENDOSCOPIC MUCOSECTOMY FOR HIGH GRADE DYSPLASIA AND EARLY ESOPHAGEAL CANCER IS AN ESSENTIAL STAGING PROCEDURE WITH LONG-TERM THERAPEUTIC BENEFIT

respectively. Both items were associated with inadequate bowel cleansing at univariate analysis. Conclusions: This study identified multiple factors affecting the quality of colonic preparation, some of which can be modified to achieve a higher degree of bowel cleansing. Important non-modifiable factors may be valuable in identifying subjects for whom more aggressive cleansing protocols should be considered.