Showing papers by "Marc Giovannini published in 2016"

Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

Abstract: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to achieve successful cannulation and sphincterotomy at minimum risk to the patient. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE suggests that difficult biliary cannulation is defined by the presence of one or more of the following: more than 5 contacts with the papilla whilst attempting to cannulate; more than 5 minutes spent attempting to cannulate following visualization of the papilla; more than one unintended pancreatic duct cannulation or opacification (low quality evidence, weak recommendation). 2 ESGE recommends the guidewire-assisted technique for primary biliary cannulation, since it reduces the risk of post-ERCP pancreatitis (moderate quality evidence, strong recommendation). 3 ESGE recommends using pancreatic guidewire (PGW)-assisted biliary cannulation in patients where biliary cannulation is difficult and repeated unintentional access to the main pancreatic duct occurs (moderate quality evidence, strong recommendation). ESGE recommends attempting prophylactic pancreatic stenting in all patients with PGW-assisted attempts at biliary cannulation (moderate quality evidence, strong recommendation). 4 ESGE recommends needle-knife fistulotomy as the preferred technique for precutting (moderate quality evidence, strong recommendation). ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary cannulation in more than 80 % of cases using standard cannulation techniques (low quality evidence, weak recommendation). When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic stent prior to precutting (moderate quality evidence, weak recommendation). 5 ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreatic biliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreatic duct occurs (moderate quality evidence, strong recommendation). In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreatic stenting (moderate quality evidence, strong recommendation). 6 ESGE recommends that mixed current is used for sphincterotomy rather than pure cut current alone, as there is a decreased risk of mild bleeding with the former (moderate quality evidence, strong recommendation). 7 ESGE suggests endoscopic papillary balloon dilation (EPBD) as an alternative to endoscopic sphincterotomy (EST) for extracting CBD stones 8 ESGE does not recommend routine biliary sphincterotomy for patients undergoing pancreatic sphincterotomy, and suggests that it is reserved for patients in whom there is evidence of coexisting bile duct obstruction or biliary sphincter of Oddi dysfunction (moderate quality evidence, weak recommendation). 9 In patients with periampullary diverticulum (PAD) and difficult cannulation, ESGE suggests that pancreatic duct stent placement followed by precut sphincterotomy or needle-knife fistulotomy are suitable options to achieve cannulation (low quality evidence, weak recommendation). ESGE suggests that EST is safe in patients with PAD. In cases where EST is technically difficult to complete as a result of a PAD, large stone removal can be facilitated by a small EST combined with EPBD or use of EPBD alone (low quality evidence, weak recommendation). 10 For cannulation of the minor papilla, ESGE suggests using wire-guided cannulation, with or without contrast, and sphincterotomy with a pull-type sphincterotome or a needle-knife over a plastic stent (low quality evidence, weak recommendation). When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation). 11 In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with laparoendoscopic rendezvous (moderate quality evidence, weak recommendation). ESGE suggests that when biliary cannulation is unsuccessful with a standard retrograde approach, anterograde guidewire insertion either by a percutaneous or endoscopic ultrasound (EUS)-guided approach can be used to achieve biliary access (low quality evidence, weak recommendation). 12 ESGE suggests that in patients with Billroth II gastrectomy ERCP should be performed in referral centers, with the side-viewing endoscope as a first option; forward-viewing endoscopes are the second choice in cases of failure (low quality evidence, weak recommendation). A straight standard ERCP catheter or an inverted sphincterotome, with or without the guidewire, is recommended by ESGE for biliopancreatic cannulation in patients who have undergone Billroth II gastrectomy (low quality evidence, strong recommendation). Endoscopic papillary ballon dilation (EPBD) is suggested as an alternative to sphincterotomy for stone extraction in the setting of patients with Billroth II gastrectomy (low quality evidence, weak recommendation). In patients with complex post-surgical anatomy ESGE suggests referral to a center where device-assisted enteroscopy techniques are available (very low quality evidence, weak recommendation).

EUS-guided Versus Percutaneous Gallbladder Drainage: Isn't It Time to Convert?

Abstract: Background and aims Endoscopic ultrasound-guided drainage (EUS-GLB) is a minimally invasive option for patients with cholecystitis who are poor surgical candidates. Compared with percutaneous drainage (PC-GLB), earlier studies have demonstrated similar efficacy with improved quality of life. We present a multicenter, international experience comparing PC-GLB and EUS-GLB in nonsurgical patients with cholecystitis. Methods All patients who underwent either PC-GLB drainage or EUS-GLB drainage from 7 centers between January 2010 and December 2015 were included. Technical success was defined as successful placement of a catheter or stent into the gallbladder. Clinical success was defined as resolution of clinical symptoms after intervention. Adverse events, length of stay, and the need for repeat interventions and/or hospitalizations were recorded for all patients. Results A total of 155 patients were included (mean age 74±14.24 y; range, 31 to 96; 56% male). Forty-two patients underwent EUS-GLB and 113 patients underwent PC-GLB. Technical success was achieved in 40 patients (95%) in the EUS-GLB group and 112 patients (99%) in the PC-GLB group (P=0.179). Clinical success was achieved in 40 patients (95%) in the EUS-GLB group and 97 patients (86%) in the PC-GLB group (P=0.157). There was no difference in hospital readmission rates between the 2 groups (14% vs. 24%; P=0.194). However, there was significantly higher number of patients requiring repeat interventions in the PC-GLB group (n=28, 24%) compared with the EUS-GLB group (n=4, 10%) (P=0.037). There was no difference in adverse events between the 2 groups. Conclusions EUS-GLB is safe and efficacious, with comparable technical and clinical success rates and no difference in adverse events. In addition, EUS-GLB offers a potential cost-saving benefit and morbidity benefit by demonstrating a decreased number of repeat interventions.

In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation.

Abstract: The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound–fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation . Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases. New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % “true” and 13 % “false” with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts). Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses.

Abstract: Background and study aims: The differential diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently suboptimal in centers that are not equipped with rapid on-site evaluation. Needle-based confocal laser endomicroscopy (nCLE) enables real-time in vivo microscopic imaging during endoscopy. This study aimed to describe nCLE interpretation criteria for the characterization of pancreatic masses, with histopathological correlation, and to perform the first validation of these criteria. Patients and methods: A total of 40 patients were evaluated by EUS-FNA combined with nCLE for the diagnosis of pancreatic masses. Final diagnosis was based on EUS-FNA histology and follow-up at 1 year. Five unblinded examiners defined nCLE criteria for adenocarcinoma, chronic pancreatitis, and neuroendocrine tumor (NET) using a set of video sequences from 14 patients with confirmed pathology (Step 1). These criteria were retrospectively validated by four independent, blinded examiners using sequences from 32 patients (Step 2). Results: nCLE criteria were described for adenocarcinoma (dark cell aggregates, irregular vessels with leakages of fluorescein), chronic pancreatitis (residual regular glandular pancreatic structures), and NET (black cell aggregates surrounded by vessels and fibrotic areas). These criteria correlated with the histological features of the corresponding lesions. In the validation review, a conclusive nCLE result was obtained in 75 % of cases (96 % correct). Statistical evaluation provided promising results, with high specificity, and negative and positive predictive values for all types of pancreatic masses. Conclusion: Considering the low negative predictive value of EUS-FNA, nCLE could help to rule out malignancy after a previous inconclusive EUS-FNA. Larger studies are required to confirm these findings and to establish the role of nCLE in the diagnosis of pancreatic masses. Trial registration: ClinicalTrials.gov (NCT01563133).

A pancreatic ductal adenocarcinoma subpopulation is sensitive to FK866, an inhibitor of NAMPT.

Abstract: Treating pancreatic cancer is extremely challenging due to multiple factors, including chemoresistance and poor disease prognosis. Chemoresistance can be explained by: the presence of a dense stromal barrier leading to a lower vascularized condition, therefore limiting drug delivery; the huge intra-tumoral heterogeneity; and the status of epithelial-to-mesenchymal transition. These factors are highly variable between patients making it difficult to predict responses to chemotherapy. Nicotinamide phosphoribosyl transferase (NAMPT) is the main enzyme responsible for recycling cytosolic NAD+ in hypoxic conditions. FK866 is a noncompetitive specific inhibitor of NAMPT, which has proven anti-tumoral effects, although a clinical advantage has still not been demonstrated. Here, we tested the effect of FK866 on pancreatic cancer-derived primary cell cultures (PCCs), both alone and in combination with three different drugs typically used against this cancer: gemcitabine, 5-Fluorouracil (5FU) and oxaliplatin. The aims of this study were to evaluate the benefit of drug combinations, define groups of sensitivity, and identify a potential biomarker for predicting treatment sensitivity. We performed cell viability tests in the presence of either FK866 alone or in combination with the drugs above-mentioned. We confirmed both inter- and intra-tumoral heterogeneity. Interestingly, only the in vitro effect of gemcitabine was influenced by the addition of FK866. We also found that NAMPT mRNA expression levels can predict the sensitivity of cells to FK866. Overall, our results suggest that patients with tumors sensitive to FK866 can be identified using NAMPT mRNA levels as a biomarker and could therefore benefit from a co-treatment of gemcitabine plus FK866.

Heterogeneity of metastatic pancreatic adenocarcinoma: Lung metastasis show better prognosis than liver metastasis—a case control study

Abstract: // Claire Decoster 1 , Marine Gilabert 1 , Aurelie Autret 1, 2 , Olivier Turrini 3 , Sandrine Oziel-Taieb 1 , Flora Poizat 4 , Marc Giovannini 1 , Patrice Viens 1 , Juan Iovanna 5 , Jean-Luc Raoul 1 1 Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France 2 Biostatistic Unit, Paoli-Calmettes Institute, Marseille 13273, France 3 Department of Digestive Surgery, Paoli-Calmettes Institute, Marseille 13273, France 4 Department of Pathology, Paoli-Calmettes Institute, Marseille 13273, France 5 Centre de Recherche en Cancerologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Marseille 13273, France Correspondence to: Raoul Jean-Luc, email: raouljl@ipc.unicancer.fr Keywords: pancreatic adenocarcinoma, lung metastases, prognosis, overall survival, local evolution Received: November 11, 2015 Accepted: May 08, 2016 Published: June 06, 2016 ABSTRACT The prognosis of metastatic pancreatic ductal adenocarcinoma (PDAC) is grim, with a median overall survival of under 1 year. In our clinical practice, we observed a few cases of isolated lung metastases from PDAC with unusually long outcomes. We compared these cases in a case-control study of lung-only vs. liver-only metastases from PDAC. From our database, we found 37 cases of lung-only metastases and paired them with 37 cases of liver-only metastases by age, tumor location and treatment. The lung-only group differed significantly from the liver-only group with respect to the following parameters: female predominance, more metachronous cases, fewer nodules per patient, and smaller increases in tumor markers. Local invasion parameters (i.e., arterial or venous involvement) were not significantly different. The outcomes were significantly different, with a median overall survival from the occurrence of metastases of 20.8 vs. 9.1 months and a median progression-free survival of 11 vs. 3.5 months. In conclusion, this case-control study seemed to confirm that lung-only PDAC metastases have prognoses different from those of liver-only metastases. A better understanding of the mechanisms underlying these differences will help identify abnormalities associated with tumor aggressiveness.

Efficiency and safety of endoscopic resection in the management of subepithelial lesions of the stomach.

Abstract: BackgroundGastric subepithelial tumors represent a diagnostic and therapeutic challenge, given their histologic heterogeneity and potential malignant behavior.ObjectiveThe objective of this article...

Treatment of Pancreatic Adenocarcinoma in Elderly Patients over 75 Years of Age: A Retrospective Series of 129 Patients

Abstract: To better know the presentation and outcome of pancreatic adenocarcinoma in patients above 75 years of age. Retrospective analysis of consecutive patients with a pancreatic adenocarcinoma seen in the Comprehensive Cancer Center of Marseille between January 2002 and January 2012 was used. During these 10 years, 129 patients older than 75 years of age were seen, 61 females and 68 males, median age 78. At diagnosis, the tumor was metastatic in 45 %. First line treatments were: surgical resection in 22 cases, radio-chemotherapy in 20 cases (1 operated on later), systemic chemotherapy in 59 cases, and best supportive care alone in 28 cases. Resection was possible in 19 cases and was R0 in 17; post-operative mortality was 0 %, and half received adjuvant chemotherapy. Median overall survival was 43 months with a 2-year overall survival of 64 %. For locally advanced tumor, 16 received best supportive care and 33 a specific treatment (20 cases of radio-chemotherapy). Median overall survival was 9.1 months and 2-year overall, survival was 6.1 %. Among the 58 metastatic patients, 79 % received systemic chemotherapy (most by gemcitabine); tolerance was correct in half. Median overall survival was 4.7 months, with a 2-year overall survival of 5.3 %. Surgery of pancreatic adenocarcinoma is feasible and safe in elderly patients with good outcomes. In advanced and metastatic patients, the outcome is poor despite a correct tolerance of systemic chemotherapy. Randomized trials specially designed for this population are urgently needed.

Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases.

Abstract: Endoscopic ultrasonography (EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration The development of EUS-guided drainage of the bilio-pancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro-intestinal, bilio-pancreatic and lymph node lesions In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations

Expression of Genes with Copy Number Alterations and Survival of Patients with Pancreatic Adenocarcinoma.

Abstract: Background/Aim: Individual molecular information might improve management of pancreatic adenocarcinoma. To identify actionable genes, at the transcriptional level, we investigated candidate genes that we had previously identified using array-comparative genomic hybridization (aCGH). Materials and Methods: We collected 10 public gene-expression datasets, gathering a total of 524 pancreatic samples (105 normal and 419 malignant tissues). Based on our previous aCGH analysis, we searched for genes differentially expressed between normal and malignant samples and genes associated with survival. Results: Among genes amplified/gained by aCGH, 48% were overexpressed in malignant tissues. The majority of these genes were related to apoptosis, cell-cycle regulation and differentiation. Among genes located in areas of loss, 41% were underexpressed in malignant tissues; most of them were involved in ion transport, homeostasis maintenance and fatty acid metabolism. Survival analysis identified genes significantly related to shorter (n=17) or longer (n=29) survival. Conclusion: Some of these genes can be further investigated as potential prognostic markers. the tumor is the only potentially curative treatment. However, fewer than 20% of patients are eligible for surgery. The median survival of patients with inoperable non-metastatic or metastatic pancreatic cancer is close to 6 months and 5-year survival is nil. Inoperability and poor prognosis are due to late diagnosis, rapid tumor progression (>80% of patients display

Neoplastic Barrett’s oesophagus and long-term follow-up after endoscopic therapy: complete histological eradication of Barrett associated with high-grade dysplasia significantly decreases neoplasia relapse

Abstract: Endotherapy (ET) has replaced surgery as the first-line treatment of high-grade dysplasia (HGD)/superficial ECA (ECAs) from Barrett’s oesophagus (BO). However, long-term follow-up and predictive factors of relapse are not so well studied. The aim of the following study was to evaluate the efficiency of ET for treatment of HGD/ECAs and to determine factors of long-term efficiency. ET procedures were manually reported and registered in a hospital data base from March 2000 to July 2010. Inclusion criteria were HGD/ECA on pre-resection biopsies, complete histological and sufficient oncological resection of HGD/ECAs, and complete macroscopic resection of metaplastic BO. Sixty patients (53 men, mean age = 65 years) were included. Median follow-up was 66 months [range 42–80]. Complete eradication of residual histological metaplastic BO occurred in 29 patients (48 %). Relapse rate at 36 months was 16.6 % (n = 10) and was unchanged at 60 months of follow-up. There was only one relapse (3.4 %) in case of complete eradication of metaplastic BO and 9 (31 %) in case of incomplete eradication. In univaried and multi-varied analysis, complete eradication of metaplastic BO (p < 0.05) and BO length <5 cm (p < 0.05) were predictive of neoplastic BO non relapse. The length of BO remained a prognostic factor for disease-free survival (DFS). When these preponderant data were cancelled out in multi-varied analysis, complete eradication of BO was a prognostic factor for DFS (p < 0.05). Complete histological eradication of BO by ET significantly decreases the rate of neoplasia relapse.