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BACKGROUNDA significant gap in pancreatic ductal adenocarcinoma (PDAC) patient’s care is the lack of molecular parameters characterizing tumors and allowing a personalized treatment. The goal of this study was to examine whole PDAC transcriptomic profiles to define a signature that would predict aggressiveness and treatment responsiveness better than done until now.METHODS AND PATIENTSTumors were obtained from 76 consecutive resectable (n=40) or unresectable (n=36) tumors. PDAC were transplanted in mice to produce patient-drived xenografts (PDX). PDX were classified according to their histology into five groups, from highly undifferentiated to well differentiated. This classification resulted strongly associated with tumors aggressiveness. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n=598) of resected tumors; ii/ 60 advanced tumors obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRINOX treated metastatic tumors.RESULTSA unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumors (e.g. 308 consecutive resected PDAC, HR=0.321 95% CI [0.207;0.5] and 60 locally-advanced or metastatic PDAC, HR=0.308 95% CI [0.113;0.836]). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumor response: -0.67, p-value < 0.001).CONCLUSIONWe identified a transcriptomic signature (PAMG) that, unlike all other stratification schemas already proposed, classifies PDAC along a continuous gradient. It can be performed on formalin-fixed paraffin-embedded samples and EUS-guided biopsies showing a strong prognostic value and predicting mFOLFIRINOX responsiveness. We think that PAMG could unify all PDAC preexisting classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient.Trial RegistrationThe PaCaOmics study is registered atwww.clinicaltrials.govwith registration numberNCT01692873. The validation BACAP study is registered atwww.clinicaltrials.govwith registration numberNCT02818829.

Additional file 2: Supplementary Table 5. Overall Survival before and after matching.

Additional file 1: Supplementary Table 4. Matching process.

Additional file 2. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Additional file 1. CONSORT 2010 checklist of information to include when reporting a randomised trial

Over the last two decades, EUS-guided hepaticogastrostomy (EUS-HGS) has emerged as a therapeutic alternative for patients with biliary obstruction and failed ERCP. Percutaneous transhepatic biliary drainage (PTBD) as the gold standard is associated with relevant morbidity and need for re-intervention. The aim of our work was to evaluate in a phase II study the safety and efficacy profile of EUS-HGS. A PTBD arm was considered a control group.We conducted a prospective, randomized, noncomparative phase II study in three French tertiary centers involving patients with benign or malignant obstructive jaundice after failure of ERCP. Patients were randomized to either PTBD or EUS-HGS.Fifty-six patients (mean age 64 years) have been included between 2011 and 2015. Twenty-one underwent PTBD and thirty-five were drained using EUS-HGS. An interim analysis after the inclusion of 41 patients revealed an unexpected high 30-day morbidity rate for PTBD (13 out of 21 patients), justifying to stop randomization and inclusion in this control arm in 2013. The primary objective was reached with 10 out of the 35 EUS-HGS patients (28.6%) having observed complications (90%-level bilateral exact binomial confidence interval [CI] [16.4%-43.6%], left-sided exact binomial test to the objectified 50% unacceptable rate P = 0.0083). Both methods achieved comparable technical success rate (TSR) and clinical success rate (CSR) (TSR: PTBD 100% vs. EUS-HGS 94.3%, P = 0.28; CSR: PTBD 66.7% vs. EUS-HGS 80%, P = 0.35). Long-term follow-up showed EUS-HGS patients being at lower risk for re-intervention (relative risk = 0.47, 95% CI [0.27-0.83]).In cases of ERCP failure, EUS-HGS is a valuable alternative for biliary drainage with a high TSR and CSR. PTBD is associated with an unacceptable 30-day morbidity rate, whereas EUS-HGS seems to have a decent safety profile, suggesting that it may be the treatment of choice in appropriately selected patients.

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Conventional haematoxylin, eosin and saffron (HES) histopathology, currently the gold-standard for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context., Comment: 18 pages, 5 figures

A rare case of refractory ascites caused by benign portal vein stenosis after pancreatoduodenectomy (PD) is reported. A dogma claims that ascites is found in portal hypertension with an intrahepatic block only. However, in the postoperative state, the pathophysiologic condition is altered, which made diagnosis difficult. A 69-year-old man who had undergone PD for lower bile duct carcinoma in situ, developed in postoperative course a pseudoaneurysm of the common hepatic artery successfully treated by stent graft. Six months later, the patient developed refractory ascites. CT scan revealed a severe stricture in the main trunk of the portal vein, probably due to extrinsic compression by the stent in the hepatic artery. Percutaneous transhepatic portography was performed and stent-graft was placed over the stenotic segment. Portal blood flow was corrected immediately. One week after the stenting procedure the patient was free of ascites and control physical and biochemical examination three years later is completely normal.

Therapeutic endoscopy plays a major role in the management of gastrointestinal (GI) neoplasia. Its indications can be generalized into four broad categories; to remove or obliterate neoplastic lesion, to palliate malignant obstruction, or to treat bleeding. Only endoscopic resection allows complete histological staging of the cancer, which is critical as it allows stratification and refinement for further treatment. Although other endoscopic techniques, such as ablation therapy, may also cure early GI cancer, they can not provide a definitive pathological specimen. Early stage lesions reveal low frequency of lymph node metastasis which allows for less invasive treatments and thereby improving the quality of life when compared to surgery. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are now accepted worldwide as treatment modalities for early cancers of the GI tract.

4150 Background: Pancreatic ductal adenocarcinoma (PDAC) has poor outcome and surgical resection remains the only curative treatment. Post-operative (Post-Op) chemotherapy (CT) improves survival and FOLFIRINOX (FFX) regimen is the standard of care. Increasing number of patients with borderline resectable (BL) or locally advanced (LA) disease are treated with pre-operative (Pre-Op) CT with FFX. However, the benefit of Post-Op CT after Pre-Op FFX remains unclear. The aim of this study was to analyze the impact on survival of Post-Op CT in patients with resected BL or LA PDAC after Pre-Op FFX CT. Methods: 116 consecutive patients treated at the Institut Paoli-Calmettes comprehensive cancer center between 2014 and 2020 were retrospectively analyzed. All patients underwent pancreatectomy after Pre-Op FFX for a BL or LA PDAC. Patients who progressed or died within 3 months after surgery were excluded from the analysis. We compared median relapse-free survival (mRFS) and median overall survival (mOS) defined by time from surgery to relapse or death in patients who received or not Post-Op CT. Results: 116 patients (80% BL, 20% LA) were included: 82 received Post-Op CT (CT+) and 34 did not (CT-). The median number of Pre-Op FFX cycles was 4 in the CT+ group vs 6 in the CT- group. 24 (29.3%) patients received Post-Op FFX, 37 (45.1%) received Gemcitabine, 9 (11%) received Gemcitabine + Capecitabine, and 9 (11%) received a 5FU-based CT. Median time between surgery and first Post-Op CT cycle was 63 days. No difference in mRFS nor in mOS were found between CT+ and CT- groups: mRFS 15.0 vs 13.6 months, HR 1.1 [IC95% 0.69–1.77] and mOS 33.8 vs 36.1 months, HR 0.94 [IC95% 0.55–1.60]. Among patients with pathologic node positive disease (N+) (n = 79), mRFS was 13.9 months in the CT+ group vs 6.9 months in the CT- group (HR 0.68 [IC 0.35 – 1.19]), and mOS was 31.8 months in the CT+ group vs 16.5 months in the CT- group (HR 0.96 [IC95% 0.51-1.81]). Patients who received peri-operative (Peri-Op) FFX (n = 24) experienced longer mOS compared to patients who received Gemcitabine Post-Op CT: NR vs 33.8 months, HR 0.45 [IC95% 0.25-1.02]. Patients who received Peri-Op CT for a total of six months or more (n = 31) had increased mOS (55 vs 32 months, HR 0.61 [IC 95% 0.37- 1.11] and mRFS (16 vs 14 months HR 0.80, [IC95% 0.50 -1.31]) than patients receiving less than 6 months Peri-Op CT (n = 85) Conclusions: Post-Op CT does not clearly impact survival in BL or LA pancreatic cancer pretreated with Pre-Op FFX. We observed a trend in the N+ population for a survival benefit. Peri-Op FFX was associated with longer survival than Gemcitabine Post-Op regimen. Further randomized data are needed to assess the impact of Peri-Op FFX for these patients

Item does not contain fulltext BACKGROUND: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. METHODS: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. CONCLUSIONS: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed. Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD. Results: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the First choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended. Conclusion: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard of care for the creation of an endoscopic cystenterostomy in patients with pancreatic walled-off necrosis (WON); 95.5% (21/22) recommended large diameter (d=15 mm) LAMS for drainage in patients with WON; 54.5% (12/22) would not dilate LAMS after placement into the WOPN; 86.4% (19/22) would not perform endoscopic necrosectomy during the same procedure as the creation of the cystenterostomy; 45.5% (10/22) recommend that agents, such as diluted hydrogen peroxide, should be used to lavage the peri-pancreatic fluid collection (PFC) cavity in patients with WON; and 45.5% (10/22) considered a naso-cystic or other tube to be necessary for lavage of WON after initial drainage. The mean optimal interval recommended for endoscopic necrosectomy procedures after EUS-guided drainage was 6.23 days. The mean optimal interval recommended for repeat imaging in patients undergoing endoscopic necrosectomy was 12.32 days. The mean time recommended for LAMS removal was 4.59 weeks. This is the first worldwide survey on the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need to establish a best practice consensus.