Anne-Laure Pelletier

Pancreas Divisum Is Not a Cause of Pancreatitis by Itself But Acts as a Partner of Genetic Mutations

OBJECTIVES:The role of pancreas divisum (PD) as a cause of acute recurrent or chronic pancreatitis (AR/CP) is still a matter of debate.METHODS: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.RESULTS: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).CONCLUSIONS: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.

Clinical outcome after a totally implantable venous access port-related infection in cancer patients: a prospective study and review of the literature.

AbstractMorbidity and mortality after a totally implantable venous access port (TIVAP)-related infection in oncology patients have rarely been studied. We conducted this study to assess the incidence and factors associated with the following outcome endpoints: severe sepsis or septic shock at presentation, cancellation of antineoplastic chemotherapy, and mortality at week 12. We conducted a prospective single-center observational study including all adult patients with solid cancer who experienced a TIVAP-related infection between February 1, 2009, and October 31, 2010. Patients were prospectively followed for 12 weeks. Among 1728 patients receiving antineoplastic chemotherapy during the inclusion time, 72 had an episode of TIVAP-related infection (4.2%) and were included in the study (median age, 60 yr; range, 28–85 yr). The incidence of complications was 18% for severe sepsis or septic shock (13/72 patients), 30% for definitive cancellation of antineoplastic chemotherapy (14/46 patients who still had active treatment), and 46% for death at week 12 (33/72 patients). Factors associated with severe sepsis or septic shock were an elevated C-reactive protein (CRP) level and an infection caused by Candida species; 4 of the 13 severe episodes (31%) were due to coagulase-negative staphylococci (CoNS). Factors associated with death at week 12 were a low median Karnofsky score, an elevated Charlson comorbidity index, the metastatic evolution of cancer, palliative care, and an elevated CRP level at presentation. Hematogenous complications (that is, infective endocarditis, septic thrombophlebitis, septic pulmonary emboli, spondylodiscitis, septic arthritis, or organ abscesses) were found in 8 patients (11%). In conclusion, patients’ overall condition (comorbidities and autonomy) and elevated CRP level were associated with an unfavorable clinical outcome after a TIVAP-related infection. Candida species and CoNS were responsible for severe sepsis or septic shock.

Acute pancreatitis in patients operated on for intraductal papillary mucinous neoplasms of the pancreas: frequency, severity, and clinicopathologic correlations.

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.Abbreviation: AP - acute pancreatitis, IPMN - intraductal papillary mucinous neoplasms of the pancreas

Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy

Background Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. Methods Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. Results 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohns colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). Conclusions Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. Trial registration number IRB 001508, Paris 7 University.

CFTR Gene Mutation in Patients with Apparently Idiopathic Pancreatitis: Lack of Phenotype-Genotype Correlation

Background and Aims: 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. Results: 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. Conclusions: 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.

Su1229 Definitions of the Endoscopic Lesions in Crohn's Disease: Reproductibility Study and GETAID Expert Consensus

Background: In the era of biologics, mucosal healing became a therapeutic target in Crohns disease (CD) patients, however, this outcome is difficult to evaluate in daily practice because it induce the need of repeated colonoscopies. Diffusion-weighted magnetic resonance enterocolonography (DW-MREC) has shown good accuracy to detect and assess inflammatory activity in CD [1] [2]. We aimed to assess the correlation between endoscopic lesions and DW-MREC parameters i.e. Apparent Diffusion Coefficient (ADC) and Clermont score (CS) [2].Methods: In this prospective study, all the patients underwent consecutively DW-MREC with no bowel cleansing, with no rectal enema [2] and colonoscopy within 4 weeks (mean interval=17±11 days). Radiologists were blinded from endoscopic findings and endoscopists were blinded from radiologic findings. Results are given in mean ± standard deviation. Results: Among the 43 CD patients, 9 (20.5%) had previous intestinal surgery. CDAI, CRP and fecal calprotectin value were 179±93, 31.1±8.0g/L and 1172.9±730.3μg/g, respectively. The CDEIS, SES-CD and CS were 6.8±7.1, 9.2+/-8.0 and 15.8±10.7, respectively. Mean ADC was inversely correlated with CDEIS (rho=-0.40; p=0.0067) and SES-CD (rho=-0.33; p=0.032). Considering the 194 segments (ileum=37, colorectal=159), ADC was inversely correlated with segmental CDEIS (-0.48; p 20mm (1.50±0.53)(p=0.0001). Considering the 37 ileal segments, CS correlated with ileal CDEIS (0.62; p 18.9 detected ulcerations with Se=0.79 and Spe=0.73. CS increased with the ulceration size (p=0.012). Conclusions: Although MRI correlated moderately with endoscopic scores, DW-MREC using ADC and Clermont score was highly effective to indirectly detect endoscopic ulcerations in CD. Thus, DW-MREC could lead to define MRI healing as a new treatment goal in CD, and could be easily used both in daily practice and in clinical trials. [1] Buisson A et al. Aliment Pharmacol ther 2013;37:537-45. [2] Hordonneau C et al. Am J Gastroenterol 2014;109:89-98.

Is the length of postoperative recurrence on the neo ileum terminal ileum predictable in Crohn's disease?

UNLABELLED Crohns disease (CD) often has a stricturing phenotype on the terminal ileum requiring surgery due to obstruction. Recurrence is frequent, creating a risk of multiple surgeries. We studied patients with ileal or ileo-colic CD who had undergone at least two surgical bowel resections between 1968 and 2008 for obstructive symptoms. AIMS The aim of this retrospective study was to determine if the length of the removed diseased bowel varied from one surgical resection to the next. The measurements obtained from radiology (small bowel follow-up), surgery and histology were compared. RESULTS Twenty four patients were included. Seventeen had 2 resections, 5 patients had 3 resections and two had 4 resections. The resected length of the diseased ileum was significantly shorter for the second intervention than for the first as assessed by radiology (median 16 cm vs 37 cm; p=0.0005), surgery (20 cm vs 40 cm; p=0.005) and histology (15 cm vs 25 cm; p=0.02) while there was no difference between the second and third resections (16 cm, 13 cm, 19.5 cm respectively) for the three types of measurements (p=NS). The surgeons assessment of the diseased segment was longer than the histologists (p=0.003). No factor was found to be significantly associated with the length of the diseased bowel on recurrence. CONCLUSION This study shows that the length of the excised neo-terminal ileum during the first episode of recurrence was shorter than during the first episode of disease and remained stable for the third episode. This is an important prognostic finding that could influence the therapeutic choices for this disease and reduce hesitation to indicate surgery.

Fatal bile duct necrosis: a rare complication of transcatheter arterial chemoembolization in a patient with endocrine hepatic metastasis.

We report the first case of fatal bile duct necrosis following transcatheter arterial chemoembolization (TACE) in a 58-year-old woman. The patient underwent two TACEs to treat hepatic metastases from an ileal endocrine tumor. Persistent cholestasis occurred after the second procedure, leading to the diagnosis of bile duct necrosis confirmed by liver biopsy. The patient died of liver failure with encephalopathy six months after the second TACE. Even though this complication is very rare, physicians should consider this diagnosis in patients who develop chronic, marked cholestasis following a TACE procedure.

P358 Risk of incident cancer in patients with inflammatory bowel disease starting anti-TNF therapy while having prior malignancy within past 5 years (GETAID survey)

electrocardiogram, telemetry, and physical exam. The PK of RPC1063 and its metabolites in plasma was evaluated using a validated LC-MS/MS assay and a non-compartmental method. Results: The upper 95% 1-sided confidence limit for QTc change from BL was always below 10 msec at both 1mg and 2mg doses, meeting pre-specified criteria to rule out a relevant QT effect of RPC1063. Assay sensitivity was demonstrated with QTc change from BL>5ms following MXF treatment. DT was well tolerated, attenuated first dose effects, and minimized decreases in HR throughout titration period. Generally, RPC1063 treatment was well tolerated. AEs, including cardiac AEs, were similar in RPC1063 and control groups, and similar to those seen previously with RPC1063. Most common AEs were administration site reaction, headache, orthostatic hypotension, dizziness, musculoskeletal chest pain and constipation. No SAEs occurred in the study. Two active metabolites that retain the S1P1R potency and selectivity of the parent were measurable at concentrations sufficient to derive PK parameters. The PK of the metabolites was similar to that of RPC1063, characterized by a late Tmax (6 8hrs), an elimination half-life of 19 22 hours, and low intersubject variability. Conclusions: The study confirmed the absence of a relevant effect of RPC1063 on QTc prolongation. Overall, the emerging favourable cardiac, safety, and PK profiles of RPC1063 support its development in UC and MS.

1096 Are Random Biopsies Still Useful for the Detection of Intraepithelial Neoplasia in IBD Patients Undergoing Surveillance Colonoscopy With Chromoendoscopy

Driffa Moussata, Matthieu Allez, Dominique Cazals-Hatem, Yoram Bouhnik, Philippe Bertheau, David Laharie, Jean-Marc Gornet, Anne Lavergne-Slove, Arnaud Bourreille, Hedia Brixi, Eric Fort, Jean-Marie Reimund, Carmen Stefanescu, Julien Branche, AnneLaure Pelletier, Philippe R. Marteau, Jacques Moreau, Marion Simon, Isabelle NionLarmurier, Franck Carbonnel, Jean-Francois Flejou, Françoise Berger, Bernard Flourie and the GETAID.