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(1) Background: Anastomotic biliary stricture (ABS) is a well-known complication of liver transplantation which can lead to secondary biliary cirrhosis and graft dysfunction. The goal of this study was to evaluate the long-term outcomes of endoscopic metal stenting of ABS in the setting of deceased donor liver transplantation (DDLT). (2) Methods: Consecutive DDLT patients with endoscopic metal stenting for ABS between 2010 and 2015 were screened. Data on diagnosis, treatment and follow-up (until June 2022) were collected. The primary outcome was endoscopic treatment failure defined as the need for surgical refection. (3) Results: Among the 465 patients who underwent LT, 41 developed ABS. It was diagnosed after a mean period of 7.4 months (+/−10.6) following LT. Endoscopic treatment was technically successful in 95.1% of cases. The mean duration of endoscopic treatment was 12.8 months (+/−9.1) and 53.7% of patients completed a 1-year treatment. After a mean follow-up of 6.9 years (+/−2.3), endoscopic treatment failed in nine patients (22%) who required surgical refection. Conclusions: Endoscopic management with metal stenting of ABS after DDLT was technically successful in most cases, and half of the patients had at least one year of indwelling stent. Endoscopic treatment long-term failure rate occurred in one fifth of the patients.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

Background Patients’ perspectives after switching from infliximab to a biosimilar have yet to be assessed. Aim To assess patients’ perspectives in a prospective manner after switching from infliximab to CT-P13. Methods 113 consecutive patients with inflammatory bowel disease (IBD) on maintenance therapy with infliximab were switched to CT-P13. Patients’ perspectives were assessed by questionnaires, including the Beliefs about Medicines Questionnaire (BMQ) and FACIT-F (questionnaire regarding fatigue), and patient-reported outcomes (IBD disability index) at the inclusion and after the fourth CT-P13 infusion. Results After one year, the patients’ perspectives did not change after the switch according to BMQ-general, BMQ-specific necessity and BMQ-specific concerns subscales. No difference was observed in the mean IBD-DI score, while a significant improvement in fatigue was observed according to the FACIT-F questionnaire. Patients’ concerns were raised about the use of biosimilars and the risks of switching with a significant improvement after switching (65% vs. 42%, respectively, p = 0.01). Fourteen (12.4%) patients experienced loss of response to CT-P13, including 12 with restoration of steroid-free clinical remission after CT-P13 dose optimization. Conclusion Although some concerns were reported, no difference was observed in patients’ perspectives after switching from infliximab to CT-P13.

International audience; Background and AimsGastrointestinal angiectasia (GIA) is the most common small bowel (SB) vascular lesion, with an inherent risk of bleeding. SB Capsule Endoscopy (SB-CE) is the currently accepted diagnostic procedure. The aim of this study was to develop a computer-assisted diagnosis (CAD) tool for the detection of GIA. MethodsDeidentified SB-CE still frames featuring annotated typical GIA and normal control still frames, were selected from a database. A semantic segmentation images approach associated with a convolutional neural network (CNN) was used for deep feature extractions and classification. Two datasets of still frames were created and used for machine-learning and for algorithm testing. ResultsThe GIA detection algorithm yielded a sensitivity of 100%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 100%. Reproducibility was optimal. The reading process for an entire SB-CE video would take 2340 seconds (39 minutes).Conclusion The developed CNN-based algorithm had high diagnostic performances allowing detection of GIA in SB-CE still frames. This study paves the way for future automated CNN-based SB-CE reading softwares.

International audience; The Computer-Assisted Diagnosis for CAPsule Endoscopy (CAD-CAP) database is a large, multicentric, public database of small-bowel (SB) capsule endoscopy (CE) still frames and video sequences, that aims to serve the development of computer-assisted diagnosis tools, from the initial steps (machine learning) to the last preclinical steps (assessment and comparison of performances). The CAD-CAP database is endorsed and maintained by the Société Française d’Endoscopie Digestive (SFED), with the support of the Société Nationale Française de Gastroentérologie (SNFGE) and MSD

Breast cancer is the leading cause of cancer deaths in Algerian women. Our aim is to analyze BRCA1 and BRCA2 genes mutations in 100 Algerian patients with a family history suggestive of genetic predisposition to breast cancer. BRCA1 and BRCA2 mutations were searched by High-Resolution Melting (HRM) analysis, followed by direct sequencing, and Multiplex Ligation- Dependent Probe Amplification (MLPA) for large deletions or duplications. An unclassified variant c.5117GC, p.Gly1706ALA and a pathogenic mutation c.2125_2126insA, p.Phe709TyrfX3 were detected in the BRCA1 gene. No large deletions or duplications were detected with MLPA. One deleterious mutation c.250CT, p.Gin84X, and one unclassified variant c.9364GA, p. Ala3122Thr were identified in BRCA2 gene. The pathological significance of this variant has to be specified and analysis of its segregation in the family and differs from those provided in the literature. Although on a limited cohort, our findings suggest a higher frequency of BRCA1/2 mutations in Algeria and it would be of interest to search for the presence of these pathogenic mutations in other family member for preventing the risk of cancer.

Essential hypertension is an important risk factor for the development of cardiovascular disease. We aim in this study to analyse the relationship between AGT M235T gene variant and ACE I/D gene variant with essential hypertension in a sample of the Algerian population of the Oran city. A case-control study has been performed in 145 subjects including; 75 hypertensives and 70 controls from Algerian population of Oran city. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to detect the M235T variant of angiotensinogen (AGT) gene and a nested PCR to determine ACE I/D gene variant. The genotypic and allelic distribution of the M235Tvariant of the AGT gene did not differ in hypertensives and normotensives group (X(2) =7.81, P

Background: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas. Objectives: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters. Materials and methods: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138). Results: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression. Conclusion: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis. Keywords: Cyclin D1, CCND1, breast cancer, immunohistochemistry, CISH.

Capsule endoscopy (CE) has become a standard non-invasive tool for small bowel (SB) examination. However, with an average number of 50,000 SB still frames per CE video, lesions can be missed and CE reading remains a timeconsuming activity. Therefore, the development of computer-aided algorithms for lesions’ detection has become an active research area in CE. Gastro-intestinal angiodysplasias (AGD) are the most common SB vascular lesions with an inherent risk of bleeding. This study aimed to develop a computer-assisted diagnosis (CAD) tool for SB-AGD detection in CE.

Background Infliximab withdrawal in patients with Crohn's disease on concomitant antimetabolite therapy is considered to be superior if obtained after a maintenance therapy period compared to induction alone. Methods We retrospectively analyzed the outcome of Crohn's disease patients treated with infliximab and an antimetabolite after infliximab was withdrawn using induction alone or induction plus at least 1-year of maintenance therapy. The time to relapse was analyzed using univariate and multivariate analyses. The model was adjusted according to the period of infliximab withdrawal. Results A total of 92 patients were included, 54 in the induction alone group. The patient characteristics were identical in the two groups except for the period of infliximab withdrawal. After a median follow-up period of 47.1 (interquartile range = 4.4–110.2) months, 66 patients (72%) experienced a relapse. After a year-adjustment, no significant difference was observed between the two groups. Based on year-adjusted multivariate analysis, the risk factors for relapse were active smoking, previous antimetabolite failure, and perianal disease. After relapse, 53 patients (80%) were retreated with infliximab. After infliximab retreatment, clinical remission was observed in 47 patients (89%) at weeks 8–10. Conclusion In Crohn's disease patients, the probability of relapse on antimetabolite therapy after infliximab withdrawal was not superior after a 1-year scheduled maintenance therapy as compared with an induction alone.

BACKGROUND Whether patients with stage IV colon cancer and unresectable distant metastases should be managed by primary colectomy followed by chemotherapy or immediate chemotherapy without resection of the primary tumor is still controversial. OBJECTIVE This study aimed to evaluate predictive factors associated with survival in patients with stage IV colon cancer and unresectable distant metastases. DESIGN This large retrospective multicentric study included 6 academic hospitals. SETTINGS This study was conducted at 6 Paris University Hospitals (Assistance Publique-Hopitaux de Paris; Saint Antoine, Henri Mondor, Ambroise Pare, Hopital Europeen Gorges Pompidou, Bichat, and Avicenne). PATIENTS Between 1998 and 2007, 208 patients with good performance status and stage IV colon cancer with unresectable distant metastases received chemotherapy, either as initial management or after primary tumor resection. MAIN OUTCOME MEASURES Survival was estimated by use of the Kaplan-Meier method. Factors associated with survival were tested by means of a log-rank test. Results were expressed as median values with 95% confidence intervals. Factors independently related to survival were tested using a Cox regression model adjusted for a propensity score. RESULTS Of the 208 patients, 85 underwent colectomy before chemotherapy, whereas 123 were treated with use of primary chemotherapy with or without biotherapy. At univariate analysis, the following factors were significantly associated with survival: primary colectomy (P = .031), secondary curative surgery (P < .001), well-differentiated primary tumor (P < .001), exclusive liver metastases (P < .027), absence of need for colonic stent (P = .009), and addition of antiangiogenic (P = .001) or anti-epidermal growth factor receptor (P = .013) drugs to chemotherapy. After Cox multivariate analysis and after adjusting for the propensity score, all of these factors, with the exception of two, colonic stent and anti-epidermal growth factor receptor drug, were found to be independently associated with overall survival. LIMITATION This study was limited by its retrospective nature. CONCLUSIONS In a selected population of patients with colon cancer and unresectable synchronous distant metastases, immediate colectomy followed by chemotherapy in association with targeted therapy was associated with longer overall survival. This strategy appears to be the most appropriate, especially for those with good performance status, well-differentiated tumors, and synchronous liver metastases only.

Background: DNA methylation is a well-known epigenetic mechanism involved in epigenetic gene regulation. Several genes were reported hypermethylated in CRC, althought no gene marker was proven to be individually of sufficient sensitivity or specificity in routine clinical practice. Here, we identified novel epigenetic markers and assessed their combined use for diagnostic accuracy. Methods: We used methylation arrays on samples from several effluents to characterize methylation profiles in CRC samples and controls, as established by colonoscopy and pathology findings, and selected two differentially methylated candidate epigenetic genes (NPY, PENK). To this gene panel we added WIF, on the basis of being reported in literature as silenced by promoter hypermethylation in several cancers, including CRC. We measured their methylation degrees by quantitative multiplex-methylation specific PCR (QM-MSP) on 15 paired carcinomas and adjacent non-cancerous colorectal tissues and we subsequently performed a clinical validation on two different series of 266 serums, subdivided in 32 CRC, 26 polyps, 47 other cancers and 161 with normal colonoscopy. We assessed the results by receiver operating characteristic curve (ROC), using cumulative methylation index (CMI) as variable threshold. Results: We obtained CRC detection on tissues with both sensitivity and specificity of 100%. On serum CRC samples, we obtained sensitivity/specificity values of, e.g., 87%/80%, 78%/90% and 59%/95%, and negative predictive value/positive predictive value figures of 97%/47%, 95%/61% and 92%/70%. On serum samples from other cancers we obtained sensitivity/specificity of, e.g, 89%/25%, 43%/80% and 28%/91%. Conclusions: We showed the potential of NPY, PENK, and WIF1 as combined epigenetic markers for CRC diagnosis, both in tissue and serum and tested their use as serum biomarkers in other cancers. We optimized a QM-MSP for simultaneously quantifying their methylation levels. Our assay can be an effective blood test for patients where CRC risk is present but difficult to assess (e.g. mild symptoms with no CRC family history) and who would therefore not necessarily choose to go for further examination. This panel of markers, if validated, can also be a cost effective screening tool for the detection of asymptomatic cancer patients for colonoscopy.