Philippe Lévy

Publications (69)200.82 Total impact

• Article: Smoking and the course of recurrent acute and chronic alcoholic pancreatitis: a dose-dependent relationship.

  Vinciane Rebours, Marie-Pierre Vullierme, Olivia Hentic, Frédérique Maire, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: Smoking has been shown to affect the course of alcoholic chronic pancreatitis (ACP). However, a dose-dependent relationship between ACP course and the amount of tobacco consumption has not been studied. All consecutive smokers with ACP were included prospectively. Thresholds were defined at 10, 15, 20, and 30 pack-years (p.y.) to assess the relationship between tobacco intake and ACP complications. Statistical adjustment on alcohol intake was performed. One hundred eight patients (male, 86%) were included. The median tobacco intake was 30 p.y. (range, 3-90 p.y.) Pancreatic calcifications and duct abnormalities were observed in 70% and 73%, respectively. Pancreatic exocrine insufficiency and diabetes mellitus were observed in 36% and 30%, respectively. No differences in ACP outcome were seen at 10-p.y. threshold. At a 15-p.y. threshold, ACP diagnosis was made earlier (36 versus 46 years; P = 0.0036). At a 20-p.y. threshold, ACP occurred earlier (P = 0.0002), and the patients had more often calcifications (P = 0.05). Similar results were observed at the 30-p.y. threshold, but additionally pancreatic exocrine insufficiency occurred earlier (P = 0.04). Tobacco intake accelerates the course of ACP in a dose-dependent fashion, apart from the amount of alcohol intake. A major threshold effect is seen in 20 p.y.
  Pancreas 11/2012; 41(8):1219-24. · 2.39 Impact Factor
• Article: FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts.

  Cindy Neuzillet, Olivia Hentic, Benoît Rousseau, Vinciane Rebours, Léïla Bengrine-Lefèvre, Franck Bonnetain, Philippe Lévy, Eric Raymond, Philippe Ruszniewski, Christophe Louvet, Pascal Hammel
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  ABSTRACT: To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts. All consecutive patients with histologically confirmed, metastatic PAC and World Health Organization performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m(2) on day 1 and leucovorin 400 mg/m(2) followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus, then 5-FU 2400 mg/m(2) as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m(2) on day 1 and leucovorin 400 mg/m(2), then 5-FU 2400 mg/m(2) as a 46-h infusion and irinotecan 100 mg/m(2) repeated on day 3, biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010. Tumor response, time to progression (TTP), overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied. Subgroup analyses were performed to search for prognostic factors. Sixty-three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9% were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n = 19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480 cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95% CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic death. PS 2 was significantly associated with poor TTP [hazard ratio (HR): 16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004). The FOLFIRI regimen had an acceptable toxicity and an interesting efficacy in our study, limited to patients in good condition (PS 0-1).
  World Journal of Gastroenterology 09/2012; 18(33):4533-41. · 2.47 Impact Factor
• Article: Extrahepatic portal venous system thrombosis in recurrent acute and chronic alcoholic pancreatitis is caused by local inflammation and not thrombophilia.

  Vinciane Rebours, Larbi Boudaoud, Marie-Pierre Vullierme, Dominique Vidaud, Bertrand Condat, Olivia Hentic, Frédérique Maire, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: Extrahepatic portal venous system thrombosis (EPVST) occurs in 13% of patients with either recurrent acute (AP) or chronic (CP) alcoholic pancreatitis. The role of thrombophilia has never been assessed in this entity. All consecutive patients with alcoholic AP or CP were included in a prospective study. All patients underwent a computerized tomography (CT) scan of the pancreas to evaluate EPVST as well as thorough testing for thrombophilia (protein C, S, and antithrombin deficiency, factor II, factor V, and JAK2 gene mutations, homocystein, biological antiphospholipid syndrome). A total of 119 patients (male, n=100 (84%); smokers, n=110 (92%)) were included. EPVST was found in 41 patients (35%). The portal, superior mesenteric, or splenic veins were involved in 34%, 24%, and 93% of patients, respectively. Thrombophilia was identified in 18% (n=22), including the biological antiphospholipid syndrome, factor V Leiden mutation, and factor II G20210A gene mutation in 21 (17.6%), 2 (1.6%), and 1 patient (0.8%), respectively. On univariate analysis, the factors associated with EPVST were smoking (RR=1.6 (1.38-1.85), P=0.03), pseudocysts (RR=2.91 (1.29-6.56), P=0.008), a pseudocyst in the pancreatic tail (P=0.03), a high CT severity index for AP (P=0.007), and pancreatic parenchymal necrosis (P=0.02). The presence of hemostatic risk factors was not associated with an increased risk of EPVST. On multivariate analysis, only pseudocysts were associated with EPVST (hazard ratio: 6.402; 95% confidence interval (1.59-26.54), P=0.009). EPVST is found in 35% of patients with acute/chronic alcoholic pancreatitis. Local inflammation appears to be the major predisposing condition. The presence of some form of thrombophilia does not increase the risk of EPVST and should not be systematically searched for in case of EPVST.
  The American Journal of Gastroenterology 07/2012; 107(10):1579-85. · 7.28 Impact Factor
• Article: The long term risk of malignancy in patients with branch duct intraductal papillary mucinous neoplasms of the pancreas.

  Wafaa Khannoussi, Marie Pierre Vullierme, Vinciane Rebours, Frédérique Maire, Olivia Hentic, Alain Aubert, Alain Sauvanet, Safi Dokmak, Anne Couvelard, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: In patients (pts) with branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN), the risk of malignant progression is well described at short- and mid-term. Few data beyond 5 years are available. Prospective study in consecutive patients (pts) with BD-IPMN and follow-up (F/U) ≥60 months to assess long term risk of malignant progression. All computed tomographies and magnetic resonance cholangiopancreatographies performed every 1 or 2 years (depending on the maximum size of cyst) were read by the same radiologist. EUS was performed in case of occurrence of main pancreatic duct (MPD) dilation or mural nodule >5 mm. Size increase was considered significant if >5 mm. Size variation, criteria suggestive of malignancy, operative therapy and pathology were recorded. 53 pts were included (median age at diagnosis: 61 years, median F/U: 84 months (range: 60-132) including 5 F/U >120 months). Lesions were stable in 38 pts (72%). Size increased in 8 pts (15%) (median increase : 11 (5-33) mm) without mural nodule (MN). One of those was operated on (low-grade dysplasia). A MN appeared in 5 pts (9%). ≥5 mm in 2 pts (5 and 15 mm) who were operated on (intermediate-grade dysplasia in both). The 3 remaining pts (MN < 5 mm) were carefully followed-up. Invasive advanced carcinoma occurred in 2 pts, both after 84 months F/U. In one of these, no imaging changes were noted 12 months before diagnosis of malignancy. In BD-IPMN, the risk of malignant evolution persists after 60 months F/U including invasive carcinomas. F/U imaging surveillance is still necessary beyond this delay in patients fit for potential surgery.
  Pancreatology 05/2012; 12(3):198-202. · 1.99 Impact Factor
• Article: Recurrence after surgical resection of gastrinoma: who, when, where and why?

  Frédérique Maire, Alain Sauvanet, Anne Couvelard, Vinciane Rebours, Marie-Pierre Vullierme, Rachida Lebtahi, Olivia Hentic, Jacques Belghiti, Pascal Hammel, Philippe Lévy, Philippe Ruszniewski
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  ABSTRACT: Surgery prolongs survival in patients with gastrinomas, but postoperative recurrences are frequent and controversies still exist about the optimal surgical procedures. The aim of this study is to analyze biological and morphological recurrences and to search for risk factors. Between 1990 and 2008, 22 patients (five with multiple endocrine neoplasia type 1) who underwent curative resection for gastrinoma were evaluated every 6 months for biological and morphological recurrences. All patients were disease-free postresection. The median postoperative follow-up was 37 months (range, 7-204 months). A biological recurrence was observed in 59% of cases, after a median time of 16.5 months (range, 7-90 months). A morphological recurrence was reported in 32% of cases, in the liver (86%) or lymph nodes (43%), after a median time of 21 months (range, 8-91 months). The median delay between biological and morphological recurrence was 3 months (range, 0-69 months). At recurrence, all patients were offered a second treatment (surgical resection in 71% of cases). One and 5 year overall survival were 100 and 76%, respectively. One and 5 year biological disease-free survival (DFS) were 76 and 27%, respectively. One and 5 year morphological DFS were 90 and 62%, respectively. Tumor size of at least 20 mm (P=0.008) and pancreatic location (P=0.04) of the primary tumor had significant effect on morphological DFS. Overall survival was significantly lower in patients with primary tumor of at least 20 mm (P=0.01). (a) Recurrence occurs in nearly two out of three patients operated upon for gastrinoma, most often detected through biological tests; (b) lymph nodes and liver are the most frequent sites of relapse and patients benefit from second treatment; (c) risk factors for recurrences are as follows: size of at least 20 mm; and the pancreatic location of the primary tumor.
  European journal of gastroenterology & hepatology 04/2012; 24(4):368-74. · 1.66 Impact Factor
• Article: Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations.

  Caroline Bertin, Anne-Laure Pelletier, Marie Pierre Vullierme, Thierry Bienvenu, Vinciane Rebours, Olivia Hentic, Frédérique Maire, Pascal Hammel, Valérie Vilgrain, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: The role of pancreas divisum (PD) as a cause of acute recurrent or chronic pancreatitis (AR/CP) is still a matter of debate. The aims of this study were to evaluate the frequency of PD diagnosed using magnetic resonance cholangiopancreatography (MRCP) in patients with AR/CP of unknown origin (n=40) after careful exclusion of all known causes and to test the hypothesis of an interaction between anatomical (PD) and functional genetic anomalies (SPINK1, PRSS1, or CFTR gene mutations or polymorphisms (n=19, 25, and 30, respectively)) that could result in AR/CP. Patients with alcohol-induced pancreatitis (n=29) and subjects who had MRCP for a nonpancreatic disease (n=45) served as controls. PD frequency was 7% in subjects without pancreatic disease, 7% in patients with alcohol-induced pancreatitis, and 5, 16, 16, and 47% in those with idiopathic, and PRSS1-, SPINK1-, and CFTR-associated pancreatitis, respectively (P<0.0001). There was no significant difference between idiopathic pancreatitis and the two control groups. The frequency of PD was higher in patients with CFTR gene-associated pancreatitis as compared with those with idiopathic and alcoholic pancreatitis (P<0.0001) and with those with SPINK1 and PRSS1 gene-associated pancreatitis (P<0.02). The frequency of PD was not different in patients with idiopathic pancreatitis as compared with controls, demonstrating that PD by itself is not a cause of pancreatitis. PD frequency was higher in patients with genetic pancreatitis, especially in those with CFTR mutations or polymorphisms, suggesting a cumulative effect of these two cofactors.
  The American Journal of Gastroenterology 12/2011; 107(2):311-7. · 7.28 Impact Factor
• Article: [The two types of auto-immune pancreatitis].

  Vinciane Rebours, Philippe Lévy
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  ABSTRACT: Autoimmune pancreatitis (AIP) is a rare disease (less than 5% of all chronic pancreatitis). AIP concept was first described 20 years ago but usual diagnostic criteria were published in 2006 (HISORt criteria). Since 2 years, a new AIP concept was described distinghing two AIP types because of differences between Asian and Western series. This new classification is based on pathological features. AIP type 1 is a systemic IgG4-related disease, defined by periductal lymphoplasmacytic infiltrate with obliterative phlebitis and storiform fibrosis and/or lymphoplasmacytic infiltrate with abundant IgG4 positive-plasma cells at immunostaining. AIP type 1 fits the classic description of the disease reported in Asian series. It appears to be a pancreatic manifestation of an IgG4-associated systemic disease which could affect numerous organs with abundant infiltration of IgG4 positive-plasma cells (biliary tree, salivary glands, lymph nodes, retroperitoneum, kidney…), associated with elevated IgG4 serum levels. AIP type 2 is characterized by the presence of granulocyte epithelial lesion on pathological examination. The inflammatory infiltrate is usually devoid of IgG4 positive-plasma cells and the IgG4 serum levels are normal. AIP type 2 represents the main pattern in Western series. No association with extra-pancreatic involvement has been described, except for inflammatory bowel disease (IBD) in 20-30% of the cases. AIP diagnosis is based on association of clinical, biological and morphological features. MRI is essential to argue for AIP diagnosis. The consensual treatment is a steroid therapy (4 weeks) according to symptoms and relapses.
  La Presse Médicale 12/2011; 41(6 Pt 1):580-92. · 0.67 Impact Factor
• Article: Do guidelines influence medical practice? Changes in management of acute pancreatitis 7 years after the publication of the French guidelines.

  Vinciane Rebours, Philippe Lévy, Jean-François Bretagne, Gilles Bommelaer, Pascal Hammel, Philippe Ruszniewski
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  ABSTRACT: The elaboration and publication of guidelines should help homogenizing the management of frequent diseases with high mortality and morbidity rates, such as acute pancreatitis. To evaluate the implementation of French guidelines on the management of acute pancreatitis (AP), and to correlate changes with a received medical training course. In 2001 (before the Consensus Conference) and 2008, the same questionnaire dealing with recommendations for AP management was sent to the French gastroenterology Units. Responses in 2001 and 2008 were compared. One hundred and seventy-six questionnaires were analyzed (public hospitals: 62%, academic hospitals: 20%, private institutions: 18%). In 2008 (vs. 2001), lipase levels were measured for establishing AP diagnosis by 99% (vs. 83%). To evaluate AP severity, a computed tomography (CT) scan was performed at 48 h by 69% (vs. 29%, P ≤ 0.001). The most used severity index was the CT Balthazar score 76% (vs. 55%, P ≤ 0.001). Antibiotic prophylaxis and artificial nutrition by enteral route were proposed by 20% (vs. 57%) and 58% (vs. 25%) for necrotizing pancreatitis. Practices were more frequently in agreement with the guidelines in public nonacademic and academic hospitals. Training course on AP management was associated with a more appropriate use of CT scan for the evaluation of AP severity and of antibiotics. Major changes were noticed since the publication of the French guidelines. Although establishing guidelines is an expensive process, it does increase compliance with best evidence-based practice.
  European journal of gastroenterology & hepatology 11/2011; 24(2):143-8. · 1.66 Impact Factor
• Article: Proteomic assessment of markers for malignancy in the mucus of intraductal papillary mucinous neoplasms of the pancreas.

  Olivier Corcos, Anne Couvelard, Delphine Dargère, Alain Sauvanet, Pascal Hammel, Valérie Paradis, Philippe Lévy, Philippe Ruszniewski, Pierre Bedossa
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  ABSTRACT: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography.
  Pancreas 11/2011; 41(2):169-74. · 2.39 Impact Factor
• Article: Immunoglobulin G4 immunostaining of gastric, duodenal, or colonic biopsies is not helpful for the diagnosis of autoimmune pancreatitis.

  Vinciane Rebours, Yann Le Baleur, Dominique Cazals-Hatem, Carmen Stefanescu, Olivia Hentic, Frédérique Maire, Yoram Bouhnik, Pierre Bedossa, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy, Anne Couvelard
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  ABSTRACT: The aim of this study was to evaluate the specificity of the infiltration of digestive tract mucosa by immunoglobulin (Ig) G4-positive plasma cells in patients with autoimmune pancreatitis (AIP), as compared with normal or inflammatory mucosa. Plasma cell infiltration, CD138 and IgG4 immunostaining of digestive biopsies were compared in 4 groups of patients: AIP type 1 (n = 19); AIP type 2 (n = 4) with inflammatory bowel disease (IBD); IBD without pancreatic disorders (n = 20); and controls (n = 26). With AIP type 1 versus controls, more plasma cells were present in the gastric mucosa of AIP (P = .02) without difference concerning IgG4+ plasma cells at any biopsy site. With AIP type 1 versus IBD, colonic mucosa was more often abnormal (P = .004), and more CD138 (P = .02) and IgG4 plasma cells (P = .0002) were counted in the colon biopsies of IBD. With AIP type 2 versus IBD, no difference for plasma cell and IgG4 infiltration was found. IgG4-positive plasma cells are not more numerous in the digestive mucosa of AIP patients than in controls, but they are more abundant in the colon of IBD patients than in AIP patients.
  Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2011; 10(1):91-4. · 5.64 Impact Factor
• Article: An overview of hereditary pancreatitis.

  Vinciane Rebours, Philippe Lévy, Philippe Ruszniewski
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  ABSTRACT: Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). Since 1996, more than 30 mutations were found. The three more common mutations are R122H, N29I and A16V. First symptoms begin since childhood, mainly before 10 years old. Main symptoms are pancreatic pain and acute pancreatitis (>70%). CP morphological changes as pancreatic calcifications are diagnosed at a median age of 22-25 years. Exocrine and endocrine pancreatic insufficiency occurred in 34% and 26% at a median age of 29 and 38 years. No clinical differences exist according to the mutation type. No excess of mortality in hereditary pancreatitis population compared to general population was found, despite a real risk of cancer. The cumulative risks of pancreatic cancer at 50, 60 and, 75 years are 10%, 18.7% and, 53.5%, respectively. The relative risk of cancer increases in smokers and is evaluated to 8.55. Hereditary pancreatitis diagnosis permits to propose an adapted management in expert centres.
  Digestive and Liver Disease 09/2011; 44(1):8-15. · 3.05 Impact Factor
• Article: Gemcitabine in elderly patients with advanced pancreatic cancer.

  Olivia Hentic, Chantal Dreyer, Vinciane Rebours, Magaly Zappa, Philippe Lévy, Eric Raymond, Philippe Ruszniewski, Pascal Hammel
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  ABSTRACT: To assess feasibility, tolerability and efficacy of gemcitabine-based chemotherapy in patients ≥ 75 years old with advanced pancreatic cancer. All consecutive patients ≥ 75 years old with advanced pancreatic adenocarcinoma were included in this retrospective study. Necessary criteria to receive chemotherapy were: performance status 0-2, adequate biological parameters and no serious comorbidities. Other patients received best supportive care (BSC). Thirty-eight patients (53% women, median age 78 years, range 75-84) with pancreatic cancer (metastatic: n = 20, locally advanced: n = 18) were studied. Among them, 30 (79%) were able to receive chemotherapy [median number: 9 infusions (1-45)]. Six patients (23%) had at least one episode of grade 3 neutropenia and one patient developed a grade 3 hemolytic-uremic syndrome. No toxic death occurred. Three patients (11%) had a partial tumor response, 13 (46%) had a stable disease and 12 (43%) had a tumor progression. Median survival was 9.1 mo (metastatic: 6.9 mo, locally advanced: 11.4 mo). Tolerance and efficacy of gemcitabine-based chemotherapy is acceptable in elderly patients in good condition, with similar results to younger patients.
  World Journal of Gastroenterology 08/2011; 17(30):3497-502. · 2.47 Impact Factor
• Article: Familial intraductal papillary mucinous neoplasms of the pancreas.

  Vinciane Rebours, Anne Couvelard, Jean-Luc Peyroux, Alain Sauvanet, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described. Three families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for. Symptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n=3) or fortuitous discovery (n=5). Number of cystic lesions was ≤3 (n=4) or >3 (n=4). Intraductal papillary mucinous neoplasms involved branch ducts (n=7) or both main pancreatic duct and branch duct (n=1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes). A familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.
  Digestive and Liver Disease 08/2011; 44(5):442-6. · 3.05 Impact Factor
• Article: Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions.

  Yann Le Baleur, Anne Couvelard, Marie Pierre Vullierme, Alain Sauvanet, Pascal Hammel, Vinciane Rebours, Frédérique Maire, Olivia Hentic, Alain Aubert, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: Pancreatic mucinous cystic neoplasms (MCN) are premalignant lesions whose natural history is poorly known. Whether the dysplasia grade might be determined with precision by preoperative clinical and imaging criteria is not known. We aimed to determine if CT scan data might be useful to predict the grade of dysplasia in a series of 60 histologically proven MCN. All consecutive patients who were operated on with pathological confirmation of MCN were included. Careful CT scan evaluation was reviewed without knowledge of pathological results. Imaging and pathological results were correlated. Sixty patients (59 females) were included. Low- and intermediate-grade dysplasias were identified in 47 and 3 patients (benign MCN), respectively, and high-grade dysplasia and invasive carcinoma in 7 and 3 patients (malignant MCN), respectively. Patients with benign lesions were significantly younger. None of the studied clinical data were statistically different to distinguish benign and malignant MCN, except age (42 vs. 48 years, p < 0.05). Only maximal diameter and mural nodules on CT scan were significantly more frequent in the malignant group. No malignant MCN had a maximal diameter <40 mm. At a 40-mm threshold, the sensitivity and specificity of the maximal diameter to diagnose malignant MCN were 100 and 54%, respectively. Mural nodules seen on CT scan were confirmed in all cases but one upon pathological examination of the surgical specimen. The sensitivity and specificity of the presence of a mural nodule seen on CT scan for the diagnosis of a malignant lesion were 100 and 98%, respectively. Preoperative CT scan detection of a mural nodule within a cystic pancreatic neoplasm suggestive of MCN strongly suggests malignancy. A diameter <40 mm is associated with no risk of malignancy.
  Pancreatology 01/2011; 11(5):495-9. · 1.99 Impact Factor
• Article: Outcome of patients with type 1 or 2 autoimmune pancreatitis.

  Frédérique Maire, Yann Le Baleur, Vinciane Rebours, Marie Pierre Vullierme, Anne Couvelard, Hélène Voitot, Alain Sauvanet, Olivia Hentic, Philippe Lévy, Philippe Ruszniewski, Pascal Hammel
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  ABSTRACT: Autoimmune pancreatitis (AIP) is better described than before, but there is still no international consensus for definition, diagnosis, and treatment. Our aims were to analyze the short- and long-term outcome of patients with focus on pancreatic endocrine and exocrine functions, to search for predictive factors of relapse and pancreatic insufficiency, and to compare patients with type 1 and type 2 AIP. All consecutive patients followed up for AIP in our center between 1999 and 2008 were included. Two groups were defined: (a) patients with type 1 AIP meeting HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to steroids) criteria; (b) patients with definitive/probable type 2 AIP including those with histologically confirmed idiopathic duct-centric pancreatitis ("definitive") or suggestive imaging, normal serum IgG4, and response to steroids ("probable"). AIP-related events and pancreatic exocrine/endocrine insufficiency were looked for during follow-up. Predictive factors of relapse and pancreatic insufficiency were analyzed. A total of 44 patients (22 males), median age 37.5 (19-73) years, were included: 28 patients (64%) with type 1 AIP and 16 patients (36%) with type 2 AIP. First-line treatment consisted of steroids or pancreatic resection in 59 and 27% of the patients, respectively. Median follow-up was 41 (5-130) months. Steroids were effective in all treated patients. Relapse was observed in 12 patients (27%), after a median delay of 6 months (1-70). Four patients received azathioprine because of steroid resistance/dependence. High serum IgG4 level, pain at time of diagnosis, and other organ involvement were associated with relapse (P<0.05). At the end point, pancreatic atrophy was observed in 35% of patients. Exocrine and endocrine insufficiencies were present in 34 and 39% of the patients, respectively. At univariate analysis, no factor was associated with exocrine insufficiency, although female gender (P=0.04), increasing age (P=0.006), and type 1 AIP (P=0.001) were associated with the occurrence of diabetes. Steroid/azathioprine treatment did not prevent pancreatic insufficiency. Type 2 AIP was more frequently associated with inflammatory bowel disease than type 1 AIP (31 and 3%, respectively), but relapse rates were similar in both groups. Relapse occurs in 27% of AIP patients and is more frequent in patients with high serum IgG4 levels at the time of diagnosis. Pancreatic atrophy and functional insufficiency occur in more than one-third of the patients within 3 years of diagnosis. The outcome of patients with type 2 AIP, a condition often associated with inflammatory bowel disease, is not different from that of patients with type 1 AIP, except for diabetes.
  The American Journal of Gastroenterology 01/2011; 106(1):151-6. · 7.28 Impact Factor
• Article: Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis due to serine protease inhibitor kazal type 1 and cystic fibrosis transmembrane conductance regulator mutations.

  Vinciane Rebours, Anne Couvelard, Alain Sauvanet, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
  Pancreas 08/2010; 39(6):947-8. · 2.39 Impact Factor
• Article: Fatty pancreas and increased body mass index are risk factors of pancreatic fistula after pancreaticoduodenectomy.

  Sébastien Gaujoux, Alexandre Cortes, Anne Couvelard, Séverine Noullet, Laurent Clavel, Vinciane Rebours, Philippe Lévy, Alain Sauvanet, Philippe Ruszniewski, Jacques Belghiti
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  ABSTRACT: Pancreatic fistula (PF) after pancreatoduodenectomy (PD) remains a challenging problem. The only commonly accepted risk factor is the soft consistency of the pancreatic remnant. In all, 100 consecutive patients underwent PD. All data, including commonly accepted risk factors for PF and PF defined according to the International Study Group of Pancreatic Fistula, were collected prospectively. On the pancreatic margin, a score of fibrosis and a score of fatty infiltration were assessed by a pathologist blinded to the postoperative course. PF occurred in 31% of patients. In univariate analysis, male sex, age greater than 58 years, body mass index (BMI) > or =25 kg/m(2), pre-operative high blood pressure, operation for nonintraductal papillary and mucinous neoplasm (IPMN) disease and for ampullary carcinoma, operative time, blood loss, soft consistency of the pancreatic remnant, absence of pancreatic fibrosis, and presence of fatty infiltration of the pancreas were associated with a greater risk of PF. In a multivariate analysis, only BMI > or =25 kg/m(2), absence of pancreatic fibrosis, and presence of fatty pancreas were significant predictors of PF. A score based on the number of risk factors present divided the patient population into 4 subgroups carrying a risk of PF that ranged from 7% (no risk factor) to 78% (3 risk factors) and from 0% to 81%, taking into account only symptomatic PF (grade B and C). The presence of an increased BMI, the presence of fatty pancreas, and the absence of pancreatic fibrosis as risk factors of PF allows a more precise and objective prediction of PF than the consistency of pancreatic remnant alone. A predictive score based on these 3 factors could help to tailor preventive measures.
  Surgery 02/2010; 148(1):15-23. · 3.10 Impact Factor
• Article: Acute pancreatitis in patients operated on for intraductal papillary mucinous neoplasms of the pancreas: frequency, severity, and clinicopathologic correlations.

  Anne-Laure Pelletier, Pascal Hammel, Vinciane Rebours, Anne Couvelard, Marie-Pierre Vullierme, Frédérique Maire, Olivia Hentic, Alain Aubert, Alain Sauvanet, Philippe Lévy, Philippe Ruszniewski
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  ABSTRACT: Acute pancreatitis (AP) may reveal intraductal papillary mucinous neoplasms of the pancreas (IPMN). The aims were to describe the characteristics of AP associated with IPMN and to compare patients with AP with those without AP. All patients who underwent surgery for IPMN between 1995 and 2006 were retrospectively studied. Clinical, imaging, and histological data were collected. The clinical and radiological severity of AP, the number of episodes, and recurrence after surgery were assessed. One hundred eighty-five patients were included. Sixty-four (34.6%) had at least 1 AP (median, 2; range, 1-10). The median Balthazar score was 1 (0-6). Imaging analysis showed no difference between the 2 groups except for the presence of a mass. Branch duct IPMNs were more frequent in the AP group (74.4% vs 45.3%, P = 0.001), whereas combined IPMNs were more frequent in the non-AP group (45.3% vs 21.5%, P = 0.001). There was no difference in the grade of dysplasia between AP and non-AP groups: carcinoma, 45.3% versus 56.2%; benign IPMN, 54.7% versus 43.8% (P = NS), respectively. Acute pancreatitis occurs in 34.6% of patients with IPMNs. Acute pancreatitis is not severe and often recurs. Histology showed no difference between the 2 groups.
  Pancreas 02/2010; 39(5):658-61. · 2.39 Impact Factor
• Article: CFTR gene mutation in patients with apparently idiopathic pancreatitis: lack of phenotype-genotype correlation.

  Anne-Laure Pelletier, Thierry Bienvenu, Vinciane Rebours, Dermot O'Toole, Olivia Hentic, Frédérique Maire, Pascal Hammel, Philippe Ruszniewski, Philippe Lévy
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  ABSTRACT: Despite an extensive search, no cause is found for recurrent acute/chronic pancreatitis (idiopathic pancreatitis (IP)) in about 20% of patients. In these patients, CFTR gene mutations may be identified. The aims of this study were (1) to describe the natural history of pancreatitis associated with the CFTR mutation, (2) to look for genotype-phenotype correlations, and (3) to examine the frequency of CFTR mutations in a population of patients with IP. 100 consecutive patients with IP were included between 1998 and 2005. 50% had one of the 33 most frequent CFTR gene mutations (common CF mutations, uncommon mutations causing variable phenotypes and variants of unknown significance in 28, 44 and 28%, respectively). Patients with a CFTR gene mutation were significantly younger than those without (34 vs. 40 years, p = 0.03). Duration of follow-up (3.5 vs. 3 years), proportion of patients with acute pancreatitis as first symptom (76 vs. 74%) were not significantly different. Signs of chronic pancreatitis (ductal changes and pancreatic calcifications), pseudocysts, common bile duct stenosis, exocrine or endocrine insufficiency occurred in 36, 26, 4, 10 and 12% of patients with CFTR gene mutations respectively, which was not different from patients without mutations. No phenotype-genotype correlation was observed. In patients with IP, clinical and radiological manifestations are not related to the presence of a CFTR gene mutation or to the type of mutation.
  Pancreatology 01/2010; 10(2-3):158-64. · 1.99 Impact Factor
• Article: Pathology analysis reveals that dysplastic pancreatic ductal lesions are frequent in patients with hereditary pancreatitis.

  Vinciane Rebours, Philippe Lévy, Jean-François Mosnier, Jean-Yves Scoazec, Marie-Sophie Soubeyrand, Jean-François Fléjou, Bruno Turlin, Pascal Hammel, Philippe Ruszniewski, Pierre Bedossa, Anne Couvelard
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  ABSTRACT: Hereditary pancreatitis (HP) is a risk factor for pancreatic adenocarcinoma. We performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with HP. Samples from partial pancreatectomies (n = 13) of patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1 mutations. Dysplastic lesions were described according to the PanIN classification. Eleven patients were found to have the R122H mutation in PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10 cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after surgery. PanIN lesions are frequent, severe, and occur early in the course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.
  Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2009; 8(2):206-12. · 5.64 Impact Factor