Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort.

BACKGROUND: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA. METHODS: From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity. RESULTS: Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1-12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI: 6.2-9.7) and median progression-free survival was 5.1 months (95% CI: 3.2-6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI: 16-21). No toxic deaths occurred. Grade 3-4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%). CONCLUSIONS: A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.

Anal Fistulas in Severe Perineal Crohn's Disease: Mri Assessment in the Determination of Long-Term Healing Rates.

Background & Aims: The European Crohn's and Colitis Organization recommends magnetic resonance imaging (MRI) of anal fistulas to decide on the drug/surgery strategy. No evidence is available on the long-term impact of MRI features on fistula healing. The aim of this study was to evaluate the benefit of combined drug/surgery strategies for the treatment of perianal Crohn's fistulas based on MRI factors at referral. Methods: The clinical event (anal abscess, new fistula tract, cellulitis), therapeutic intervention (introduction/optimization of immunosuppressant/biologics, anal surgery, intestinal resection, stoma), and MRI data were prospectively recorded for patients with Crohn's disease (CD) and anal fistulas. Healing was defined by fulfilment of all the following conditions: no discharge or pain, closure of the external opening of the fistula, no visible internal opening, no abscess, and no subsequent draining seton or drainage procedure performed during at least 1 year of follow-up. Results: Seventy CD patients with anal fistulas and MRI evaluations were followed for 70 months. The cumulative rates of fistula healing were 25%, 40%, 50%, and 70% at 12, 24, 36, and 72 months, respectively. Severe, complex, branched, and high fistulas were associated with a less favorable outcome. Surgical closure of the tract improved the healing rates better than treatment with biologics or thiopurines. Male sex, A1 luminal phenotype, and anal ulceration at referral were independently associated with a higher healing rate. Conclusions: Therapeutic strategies for perianal fistulizing CD require robust anatomical and healing evaluations. Combined strategies using biologics to improve both drainage and secondary closure of the fistula tracts merit further study.

Magnetic resonance imaging and clinical assessments for perianal Crohn's disease: gain and limits.

BACKGROUND: Assessment of perianal Crohn's disease remains challenging. European Crohn's and Colitis Organisation (ECCO) recommend magnetic resonance imaging (MRI) as a gold standard, but both accuracy and advantages remain limited compared to systematic clinical assessment. The aim of this study was to define their actual diagnostic value. METHODS: We performed a retrospective analysis of a prospective database of consecutive patients with perianal Crohn's disease assessed by magnetic resonance imaging and clinical examination from 2006 to 2012. At each outpatient visit, perianal activity (Perianal Disease Activity Index) and perianal phenotype (Cardiff-Hughes classification) were noted. MRI was interpreted according to Cardiff-Hughes and Van Assche classifications. RESULTS: Overall, 122 combined evaluations were assessed in 70 patients. Radiological imaging failed to show superficial ulcerations in 20/21 patients (95%) and severe ulcerations in 13/15 patients (87%). It consistently failed to diagnose anal stenosis (n=21, 100%). For fistulising lesions, the global agreement between the two methods was 71/122 (58%) in assessing complex fistulas. Clinical assessment underestimated 44/68 (65%) of multiple or ramified fistula tracts. Clinical examination failed to diagnose half of the radiological abscesses. CONCLUSIONS: Current ECCO guidelines should be applied with some caution because of the low sensitivity of MRI for the diagnosis of non-fistulising perianal disease. Combining clinical and MRI assessments improves diagnostic accuracy.