The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients.

Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates. We retrospectively analyzed the germline data of 257 PC patients among whom nearly 50% were sporadic cases. We showed similar frequencies of BRCA2 (4.9%) and ATM (4.4%) PV or likely pathogenic variants, which were not related to familial history. Based on our findings and that of the literature, we suggest including ATM gene among the panel of genes analyzed in PC patients pending the publication of prospective studies.

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.

Management of desmoid tumours: A large national database of familial adenomatous patients shows a link to colectomy modalities and low efficacy of medical treatments.

BACKGROUND: Desmoid tumours represent a major complication of familial adenomatous polyposis. Our aims were to study the factors associated with the development of desmoid tumours in familial adenomatous polyposis patients, and to describe presentation and management of desmoid tumours. METHODS AND PATIENTS: We reviewed all patients with familial adenomatous polyposis followed at our institution between 1965-2013, with either identified adenomatous polyposis coli gene mutation, or a personal and family history suggesting adenomatous polyposis coli-related polyposis. Response to treatment of desmoid tumours was assessed by Response Evaluation Criteria In Solid Tumor (RECIST) criteria. RESULTS: A total of 180 patients with familial adenomatous polyposis were included with a median follow-up of 19 years since diagnosis. Thirty-one (17%) patients developed 58 desmoid tumours, a median (range) 4.7 (0.8-41.6) years after their diagnosis of familial adenomatous polyposis. The only factor significantly associated with occurrence of desmoid tumours was the type of surgery: 12 (12%) desmoid tumours in 104 patients treated by colectomy, versus 19 (25%) desmoid tumours in 76 patients treated by proctocolectomy, p = 0.027. The localisation of desmoid tumours was: mesenteric (n = 25), abdominal wall (n = 30) or extra-abdominal (n = 3). Nineteen patients underwent 36 surgical procedures for desmoid tumours. Recurrence occurred in 26 (72%) cases and the recurrence-free survival was 2.6 (95% confidence interval (CI), 0.2-5.9) years. Thirteen patients received 27 medical treatments over a median 14 months. Objective response was observed in four (15%) patients and the median progression-free survival was nine (95% CI, 1.1-16.9) months. CONCLUSION: If confirmed, colectomy (versus proctocolectomy) should be performed in adenomatous polyposis coli-related familial adenomatous polyposis patients to avoid desmoid tumours. We show that there is a high prevalence of post-surgical recurrence and the low efficacy of available medical treatments for desmoid tumours.

Fully covered self-expanding metal stents for benign colonic strictures.

BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. PATIENTS AND METHODS: All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. RESULTS: The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.

Macroscopic and histologic regression of duodenal polyposis with FOLFOX4 chemotherapy for an ileal pouch adenocarcinoma in a patient with familial adenomatous polyposis.

Severe (stage IV) duodenal polyposis is difficult to manage in patients with familial adenomatous polyposis (FAP), with no effective medical treatment, complex endoscopic treatment modalities, and a high morbidity and mortality from pancreaticoduodenectomy. We present the case of a 44-year-old woman with FAP, stage IV duodenal polyposis, and with an ileal pouch adenocarcinoma that required surgery and adjuvant chemotherapy. Her duodenal polyposis regressed to stage II after four sessions of FOLFOX4 adjuvant chemotherapy, which avoided the need for aggressive endoscopic therapy or pancreatoduodenectomy in this patient.

Prospective multicenter evaluation of colon capsule examination indicated by colonoscopy failure or anesthesia contraindication.

BACKGROUND AND STUDY AIMS: In France, in about 5% of cases colonoscopies are incomplete or temporarily contraindicated.We tested the diagnostic yield of colon capsule endoscopy (CCE) in these patients. PATIENTS AND METHODS: In a prospective study, in 17 French centers, inclusion criteria were colonoscopy failure or general disease that excluded colonoscopy with anesthesia. Patients underwent CCE using the first-generation PillCam Colon capsule. The main end point was CCE diagnostic yield, defined as identification of a colorectal lesion that directly explained symptoms or necessitated a diagnostic or therapeutic examination. A secondary objective was to test a simplified Movi-Prep colon cleansing. Follow-up to identify missed symptomatic cancer was scheduled. RESULTS: CCE showed positive findings in 36 patients (diagnostic yield 33.6 %), among whom 23 subsequently underwent therapeutic intervention. Among 64 patients with negative capsule findings, 9 had a complementary procedure showing adenomas in only 1 case. CCE was incomplete in 7/107 patients. Colonoscopy was done in one patient to retrieve a capsule retained in the left colon, and sigmoidoscopy in 11 because the rectum was not reached. No colorectal cancer was diagnosed during the follow-up period. Colon cleansing with MoviPrep was rated good or excellent in 75.9% of cases. CONCLUSION: This study shows the feasibility and the usefulness of CCE in the situation of colonoscopy failure or contraindication. The colon capsule modality should be tested against other available approaches, such as virtual colonoscopy or repeat colonoscopy by an expert.

Cost effectiveness and projected national impact of colorectal cancer screening in France.

BACKGROUND: Colorectal cancer (CRC) is a major cause of morbidity and mortality in France. Only scanty data on cost-effectiveness of CRC screening in Europe are available, generating uncertainty over its efficiency. Although immunochemical fecal tests (FIT) and guaiac-based fecal occult blood tests (g-FOBT) have been shown to be cost-effective in France, cost-effectiveness of endoscopic screening has not yet been addressed. METHODS: Cost-effectiveness of screening strategies using colonoscopy, flexible sigmoidoscopy, second-generation colon capsule endoscopy (CCE), FIT and g-FOBT were compared using a Markov model. A 40 % adherence rate was assumed for all strategies. Colonoscopy costs included anesthesiologist assistance. Incremental cost-effectiveness ratios (ICERs) were calculated. Probabilistic and value-of-information analyses were used to estimate the expected benefit of future research. A third-payer perspective was adopted. RESULTS: In the reference case analysis, FIT repeated every year was the most cost-effective strategy, with an ICER of €48165 per life-year gained vs. FIT every 2 years, which was the next most cost-effective strategy. Although CCE every 5 years was as effective as FIT 1-year, it was not a cost-effective alternative. Colonoscopy repeated every 10 years was substantially more costly, and slightly less effective than FIT 1-year. When projecting the model outputs onto the French population, the least (g-FOBT 2-years) and most (FIT 1-year) effective strategies reduced the absolute number of annual CRC deaths from 16037 to 12916 and 11217, respectively, resulting in an annual additional cost of €26 million and €347 million, respectively. Probabilistic sensitivity analysis demonstrated that FIT 1-year was the optimal choice in 20% of the simulated scenarios, whereas sigmoidoscopy 5-years, colonoscopy, and FIT 2-years were the optimal choices in 40%, 26%, and 14%, respectively. CONCLUSIONS: A screening program based on FIT 1-year appeared to be the most cost-effective approach for CRC screening in France. However, a substantial uncertainty over this choice is still present.

Colon capsule endoscopy vs. colonoscopy in patients at average or increased risk of colorectal cancer.

BACKGROUND: Colon capsule endoscopy (CCE) is a new, non-invasive technology. AIM: To conduct a prospective, multicentre trial to compare CCE and colonoscopy in asymptomatic subjects enrolled in screening or surveillance programmes for the detection of colorectal neoplasia. METHODS: Patients underwent CCE on day one and colonoscopy (gold standard) on day two. CCE and colonoscopy were performed by independent endoscopists. RESULTS: A total of 545 patients were recruited. CCE was safe and well-tolerated. Colon cleanliness was excellent or good in 52% of cases at CCE. Five patients with cancer were detected by colonoscopy, of whom two were missed by CCE. CCE accuracy for the detection of polyps ≥ 6 mm was 39% (95% CI 30-48) for sensitivity, 88% (95% CI 85-91) for specificity, 47% (95% CI 37-57) for positive predictive value and 85% (95% CI 82-88) for negative predictive value. CCE accuracy was better for the detection of advanced adenoma, in patients with good or excellent cleanliness and after re-interpretation of the CCE videos by an independent expert panel. CONCLUSIONS: Although well-tolerated, CCE cannot replace colonoscopy as a first line investigation for screening and surveillance of patients at risk of cancer. Further studies should pay attention to colonic preparation (Clinicaltrial.gov number NCT00436514).

Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in asymptomatic patients with Lynch syndrome.

BACKGROUND AND STUDY AIMS: Patients with Lynch syndrome are at increased risk of developing small-bowel adenocarcinoma, which usually has a bad prognosis and needs to be diagnosed early. Our aim was to evaluate the yield of capsule endoscopy and CT enteroclysis in this situation. PATIENTS AND METHODS: We performed a prospective, blinded, comparative study of capsule endoscopy and CT enteroclysis in five academic centers. Thirty-five consecutive asymptomatic patients with Lynch syndrome, all with one proven deleterious mutation, were included. A double reading was performed blind for both types of examination. RESULTS: Histologically confirmed small-bowel neoplasms were diagnosed in three patients (8.6 %): one adenocarcinoma (T3N0M0) and two adenomas with low-grade dysplasia. Capsule endoscopy identified all neoplasms. CT enteroclysis raised suspicion of one neoplasm (adenocarcinoma) but missed the two others. Concordance between the two capsule readings was high with a κ value of 0.78 (95 %CI 0.55 to 1.0), which was not the case for CT enteroclysis, where the κ value was 0.15 (95 %CI -0.27 to 0.58). CONCLUSION: Curable early or advanced neoplasms in asymptomatic patients with Lynch syndrome using capsule endoscopy can be detected with a better reproducibility than with CT enteroclysis. The clinical usefulness of systematic small-bowel screening in these patients should be confirmed through large prospective studies.

Diagnostic accuracy of esophageal capsule endoscopy versus conventional upper digestive endoscopy for suspected esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIM: A video capsule similar to that used in small-bowel capsule endoscopy is now available for esophageal exploration. The aim of our study was to compare the accuracy of upper endoscopy (esophageal gastroduodenoscopy [EGE]) with esophageal capsule endoscopy (ECE) in patients at risk of esophageal squamous cell cancer (SCC). PATIENTS AND METHODS: 68 patients at risk of SCC secondary to a history of head and neck neoplasia were included in this comparison of techniques for detecting SCC and dysplasia. ECE was done using the first generation Pillcam ESO and EGE was performed in accordance with the usual practice of each center, followed by examination with 2 % Lugol staining and biopsy of unstained areas (39 neoplasia comprising 5 low grade dysplasia, 8 high grade dysplasia and 26 SCC). RESULTS: Compared with EGE with and without Lugol staining, the sensitivities of ECE for neoplasia diagnosis were 46 % and 54 %, respectively. On a per-patient basis, the sensitivity, specificity, and positive and negative predictive value of ECE were 63 %, 86 %, 77 % and 76 %, respectively, compared with EGE without staining, and 61 %, 86 %, 77 % and 73 % compared with EGE with iodine staining. Neither the ECE transit time nor the distance between the esopharyngeal line and the neoplastic lesion differed between the 21 false-negative and 18 true-positive cases diagnosed by ECE; the only difference was a smaller median diameter among false negatives ( P < 0.001). CONCLUSION: In a cohort at high risk for esophageal SCC, ECE is not sensitive enough to diagnose neoplastic lesions.

[Role of chromoendoscopy for the management of colorectal neoplasia]. / Place des colorations dans la prise en charge des néoplasies colorectales.

Early detection of colorectal neoplasia is a major aim for gastroenterologists, much more than diagnosing advanced cancer. Chromoscopy using mostly indigo-carmine dye at 0.2% is an important tool in this setting, with proven interest for the detection of flat neoplasia in specific at risk patients including Lynch syndrome and inflammatory bowel disease. No other diagnostic tool has demonstrated its superiority, or even its equivalence, to chromoscopy in these situations. With less scientific evidences, chromoscopy helps the endoscopist to delimitate neoplasia before and after endoscopic treatment, and in the specific situation of digestive polyposes. In contrast, there is no proven interest of systematic chromoscopy in the usual situation of coloscopy for cancer screening in moderate or high-risk patients. However, a frequent use of chromoscopy is probably associated with higher ability of the endoscopist, even in usual colonoscopy indications, to identify difficult colorectal lesions.

[Cancer genetics: estimation of the needs of the population in France for the next ten years]. / Oncogénétique : estimation des besoins de la population en France pour les dix ans à venir.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

Esophageal capsule endoscopy vs. EGD for the evaluation of portal hypertension: a French prospective multicenter comparative study.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is the standard method for the diagnosis of esophago-gastric varices. The aim of this prospective multicenter study was to evaluate the PillCam esophageal capsule endoscopy (ECE) for this indication. METHODS: Patients presenting with cirrhotic or noncirrhotic portal hypertension underwent ECEfollowed by EGD at the time of diagnosis. Capsule recordings were blindly read by two endoscopists. RESULTS: A total of 120 patients (72 males, mean age: 58 years; mean Child-Pugh score: 7.2) were included. Esophageal varices were detected in 74 patients. No adverse event was observed after either EGD or ECE. Seven (6%) patients were unable to swallow the capsule. The mean recording time was 204 s (range 1-876). Sensitivity, specificity, negative predictive value, and positive predictive value of ECE for the detection of esophageal varices were 77%, 86%, 69%, and 90%, respectively. Sensitivity, specificity, negative and positive predictive values of ECE for the indication of primary prophylaxis (esophageal varices > or = grade 2 and/or red signs) were 77, 88, 90, and 75%, respectively, and 85% of the patients were adequately classified for the indication (or not) of prophylaxis. Interobserver concordance for ECE readings was 79.4% for the diagnosis of varices, 66.4% for the grading of varices, and 89.7% for the indication of prophylaxis. CONCLUSIONS: This large multicenter study confirms the safety and acceptable accuracy of ECE for the evaluation of esophageal varices. ECE might be proposed as an alternative to EGD for the screening of portal hypertension, especially in patients unable or unwilling to undergo EGD.

Endoscopic resection of sporadic duodenal adenomas: an efficient technique with a substantial risk of delayed bleeding.

INTRODUCTION: Data on endoscopic resection of sporadic duodenal adenoma (SDA) are sparse; we present our results concerning safety and efficacy in a retrospective analysis of saline-assisted endoscopic resection of SDA. PATIENTS AND METHODS: The cases of all patients who underwent endoscopic resection for SDA between May 1998 and May 2006 were analyzed. Endoscopic resection was carried out using standard injection and cut methods. In some patients hemoclips and argon plasma coagulation were used, either for prophylaxis or for the treatment of procedure-related bleeding. RESULTS: Thirty-six patients with a total of 37 lesions (mean size 19 mm, range 4 - 50 mm) were analyzed. Lesions larger than 20 mm were more frequently resected piecemeal ( P = 0.022). Intraprocedural bleeding occurred in 14 % of cases, without any significant association with lesion size or the resection technique. One fatal perforation occurred. Macroscopically complete resection was achieved in 97 % of cases, as confirmed by at least one negative control endoscopy with biopsies after a mean follow-up of 15 months. Although clipping and argon plasma coagulation were not applied in any systematic way, it was noticeable that in the 20 cases in which they were used for hemostasis or prevention, no delayed bleeding was observed after the procedures. In contrast, bleeding occurred in 22 % of the 23 procedures performed without these additional techniques. CONCLUSION: Endoscopic resection is an efficient and acceptably safe technique for treating SDA. Further studies need to assess whether systematic bleeding prophylaxis will reduce the incidence of delayed hemorrhage after endoscopic resection.