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A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.

Highlights • The coronavirus 2019 (COVID-19) pandemic has significantly affected medical care worldwide. • Protective measures, the reallocation of equipment and human resources have changed the operating procedures in all departments. • From mid-April 2020 and onward, the epidemic stabilized and then receded in France, leading to a partial easing of home isolation on May 11, 2020. • The urgent endoscopy caseload outside regular working hours decreased nearly by half during the COVID-19 pandemic, compared to prior years and the expected numbers in 2020. • The number of endoscopies for suspected GIB and the number of variceal and non-variceal GIB decreased as a consequence of home isolation., Background and Study Aims The coronavirus 2019 (COVID-19) pandemic has significantly affected medical care. We surmise that the number of urgent endoscopies outside regular working hours in the Paris area decreased as a result. The objective of this study was to describe the observed number of acts during the 2020 mandatory period of home isolation, compared to the values in prior years and the expected value for 2020. Material and methods We performed a multicenter cohort study to investigate the practice of urgent endoscopy acts, outside regular working hours, in Paris and its surrounding suburbs, in the setting of the COVID-19 pandemic. We collected the number of endoscopies performed between January 17th and April 17th 2018, 2019 and 2020. We then collected clinical, endoscopic and outcome variables from the patients of years 2019 and 2020. Results From March 17th to April 17th (during home isolation), the number of acts was respectively of 147 in 2018, 137 in 2019, and 79 in 2020, lower that the expected number of 142 (-44.0%). In 2020, the number of endoscopies for suspected gastrointestinal bleeding (GIB), and findings of variceal and non-variceal bleeding decreased by 52.1%, 69.2% and 43.1% respectively, after a month of home isolation. In-hospital death rate were similar. Conclusions This study confirms that the urgent endoscopy caseload outside regular hours decreased nearly by half during the pandemic. Our results suggest a decreased number of endoscopies for suspected gastrointestinal bleeding, and findings of variceal and non-variceal bleeding.

Aneuploidy is a common feature of cancer cells and may contribute to cellular transformation and cancer development. In this study, we found that significant down-regulation of CDKN2A, CHEK2, CDCA8, TP53BP1, and CCNDBP1 led to chromosome imbalances in two diploid non-immortalized human cell lines; however, only CDKN2A inhibition enhanced cell proliferation and additionally up-regulated three cell cycle control genes: CDCA8, AURKA, and CCND. These results confirm that CDKN2A is a tumor suppressor gene driving human cancer development by inducing cell aneuploidy and cell cycle up-regulation.

Background Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. Methods IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. Results 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1–30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. Conclusion CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed.

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

Introduction Sarcopenia is a prognostic factor of esophageal carcinoma (EC) before surgery, with less convincing data reported before chemoradiotherapy (CRT). Material and methods All patients with a locally advanced EC who had been treated with upfront CRT, between 2010 and 2015, were included. The decision of surgery was made after CRT (40–50 Gy). Muscle mass was measured on a single third lumbar vertebra CT-scan slice. Sarcopenia was internationally defined as skeletal muscle index of ≤39cm2/m2 for women and ≤55cm2/m2 for men. Results were additionally analyzed according to clinical parameters, with a cut-off based on the mean skeletal muscle lumbar index (SMI) of the population studied. Results Overall, 104 patients were included (male: 69%). Mean SMI was 35cm2/m2 for women and 46cm2/m2 for men, with 81% of patients being sarcopenic (n = 84). The 3-year overall survival (OS) rate, of 34.6%, was not significantly associated with sarcopenia in the whole population. In men, there was, however, a highly significant correlation between SMI and OS (p = 0.003), which remained significant upon multivariate analysis (p = 0.02). When using the mean SMI as cut-off, sarcopenia was significantly associated with 3-year OS (43.3% vs. 26.2%, p = 0.02). Conclusion A high sarcopenia level appears negatively associated with OS in male EC patients treated with upfront CRT.

Gastrointestinal toxicities of MEK inhibitors in melanoma patients are frequent. In clinical trials, the most common digestive adverse events were nausea, vomiting, and diarrhoea. However, severe toxicities such as colitis and gastrointestinal perforation, some with fatal outcomes, have been reported. These rare but severe adverse events are not well described. We performed a retrospective analysis of all patients with stage IV and unresectable stage III melanoma treated with a MEK inhibitors at Saint-Louis Hospital, Paris, between 1 August 2013 and 15 October 2018. Among 119 patients exposed to MEK inhibitors, 78 were treated with trametinib, 19 with cobimetinib, four with binimetinib, and 18 patients with two different MEK inhibitors at separate times. All grade digestive adverse events were observed in 39 (32.7%) patients. Grade 3 and 4 adverse events occurred in 6 (5%) patients: 2 (1.7%) developed perforations, 3 (2.5%) had colitis and 1 (0.8%) had grade 4 diarrhoea. These adverse events were all reversible following a permanent discontinuation of the MEK inhibitors, or a temporary interruption followed by resumption at a dose lower than conventional posology. There were no fatal outcomes; however one patient had a permanent ileostomy. The mechanism underlying these toxicities is not well known. Clinicians should be aware of such toxicities.

International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.

Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient's treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg. Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs. Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.

BACKGROUND: Endoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to “classical” GC. METHODS: A retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC. RESULTS: Forty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis. CONCLUSIONS: This study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to “classical” GC paving for a broader use of EUS in preoperative settings.

Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first-line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 µm thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab.

Background A dysregulated T-cell response is involved in the pathophysiology of inflammatory bowel diseases (IBD). T cells expressing the NKG2D activation receptor are implicated. Here, we investigated changes in intestinal T lymphocyte subsets overtime in patients treated by biotherapy for active disease. Methods In this prospective single-centre study, patients with IBD who have started a biotherapy (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) for active disease were included. Mucosal biopsies in the inflamed segment were taken during endoscopies before treatment initiation (W0) and in the same location 14 weeks (W14) and 52 weeks (W52) after inclusion. Control biopsies were taken from 16 patients without IBD (7 ileal and 9 colonic). Immunophenotyping of isolated lymphocytes was performed by flow cytometry at each timepoint. Correlation with endoscopic response was evaluated. For Crohn’s disease (CD), the response was defined by a 50% decrease of the CDEIS score. For ulcerative colitis (UC), the response was defined by a 2 points decrease of the UCEIS Results Between February 2016 and November 2018, 85 patients were included. Forty-four were male (52%). Forty had an active CD with the most inflamed segment located for 28 in the colon and 12 in the ileum. Thirty-nine patients had active UC and 6 pouchitis. An anti-TNF was started for 51 patients (60%), Vedolizumab for 16 patients (19%) and Ustekinumab for 18 (21%). Lymphocytes phenotyping was performed at inclusion for the whole cohort, at W14 for 67 patients (79%) and at W52 for 49 patients (58%). Data concerning endoscopic response was available for all patients. At W0, IBD patients displayed higher rates of CD4 T cells and lower rates of CD8 T cells than controls (medians: 31% vs. 48% for CD4, p < 0.001 and 52% vs. 37% for CD8, p < 0.001 respectively). Endoscopic responders experienced a normalisation of these mucosal populations as compared with non-responders (W14: 58% vs. 45% for CD4, p = 0.005 and 40% vs. 28% for CD8, p = 0.03; W52 56% vs. 43% for CD4, p = 0.01 and 27 vs. 43% for CD8, p = 0.003). Results remained significant when splitting the cohort in CD and UC patients. Before treatment initiation, IBD patients displayed lower expression of NKG2D on CD8 T cells (78% vs. 94%, p < 0.001). At W52, endoscopic responders presented significantly higher expression of this marker on CD8 T cells compared with non-responders (85% vs. 68%, p < 0.001). Results remained significant in UC and CD patients. Conclusion The intestinal T cells of IBD patients with active disease present an increase of the CD4 to CD8 T-cell ratio and lower expression of NKG2D on CD8 T cells reflecting engagement of this receptor in inflammation. These T-cell parameters are normalised in endoscopic responders but not in non-responders

Stéphanie Morgant,1 Pascal Artru,2 Ammar Oudjit,3 Nelson Lourenco,4 Arnaud Pasquer,5 Thomas Walter,6 Jean-Marc Gornet,4 Alexandre Rouquette,7 Gérard Lledo,2 Catherine Brezault,1 Romain Coriat1 1Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France; 2Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France; 3Radiology Unit, Cochin Teaching Hospital, Paris, France; 4Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France; 5Digestive Surgery Unit, Edouard Herriot Teaching Hospital, Lyon, France; 6Oncology Unit, Edouard Herriot Teaching Hospital, Lyon, France; 7Pathology Department, Cochin Teaching Hospital, Paris, France Background: Computed tomography (CT) scan is a key imaging technique in the staging of gastric adenocarcinoma and therapeutic management of patients. The aim of this study was to evaluate the performance of CT scan in the staging of parietal and metastatic invasion in gastric linitis plastica group. Methods: A retrospective multicentric French study was conducted from January 2006 to December 2015 on patients with no metastatic gastric linitis plastica and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed. Results: Fifty patients were included in the linitis plastica group and 100 in the control group. Patients from the linitis group were significantly different from those from the control group with a lower age at diagnosis, a more advanced histological lesion, a more frequent ­undiagnosed peritoneal carcinomatosis, and a higher risk of R1 resection. Sensitivity and specificity of CT scan for the diagnosis of lymph node involvement were 44% and 75%, respectively, in the linitis plastica group and 55% and 60%, respectively, in the control group. The sensitivity and specificity of CT scan for the T3–T4 parietal invasion were 26% and 100%, respectively, in the linitis group and 40% and 72%, respectively, in the control group. Conclusion: CT scan has an equal sensitivity and specificity for the evaluation of lymph node and parietal involvement in gastric adenocarcinoma, including linitis plastica. CT scan remains the cornerstone of preoperative evaluation in gastric adenocarcinoma, including linitis plastica. However, CT presents a lack of sensitivity to diagnose low-volume peritoneal carcinomatosis. Keywords: computed tomography, CT scan, linitis, gastric adenocarcinoma

Summary Introduction Following publication of improved patients’ outcome using first line FOLFIRINOX for metastatic pancreatic adenocarcinoma, many physicians now prescribe it as neo-adjuvant or induction treatment for borderline and locally advanced pancreatic cancer. A pathologic complete response, rarely seen with previous preoperative regimens, is sometimes observed in these patients. The aim of this study was to assess long-term outcomes of patients presenting pathologic complete response after preoperative FOLFIRINOX usually followed by chemo-radiation therapy for non-metastatic pancreatic adenocarcinoma. Material and methods We retrospectively identified all resected patients with pancreatic cancer presenting pathologic complete response after FOLFIRINOX in 9 French centers from the AGEO group between November 2010 and May 2017. Results 29 patients were enrolled, 14 had borderline, 14 locally advanced and 1 oligo-metastatic pancreatic cancer. M/F ratio was 1.2 and the mean age was 57 years. All patients were treated with FOLFIRINOX (n = 29), de-escalated to gemcitabine (n = 1) and FOLFIRI (n = 2), and 24 (83 %) received radiation therapy after chemotherapy. Objective response rate to preoperative chemotherapy was 66% (RECIST V1.1). Only 8 patients received postoperative chemotherapy. After a median follow-up of 34 months from surgery, the median overall survival was not reached and the median disease free survival was 48 months. The 1-year and 2-year survival rates were 100% for OS and 96% and 72 % for DFS from surgery, 8 of the 9 observed recurrences were distant metastases. Conclusions The promising 1 and 2-year overall survival and disease free survival rates suggest that pathologic complete response is a major prognostic factor in resected pancreatic cancer following preoperative chemo-radiotherapy. A longer follow-up and prospective series are now necessary to confirm these encouraging results and to potentially validate pathologic complete response as a relevant surrogate marker of preoperative treatment efficacy.

To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer.We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5-7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume.Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (10%) before salvage brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%).Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy.

Summary Background Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting. Methods The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients. Results PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53- mutated and wild type groups in term of PFS (HR = 1.04; IC9 5% = 0.6–1.79) and OS (HR = 0.99; IC 95% = 0.53–1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS. Conclusions Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.

Background After intestinal resection for Crohn's disease, the severity of endoscopic recurrence in the first year following surgery is predictive of clinical outcome. Aim of the study was to assess the impact on clinical recurrence of tailored therapy based on endoscopic findings in the first year following surgery for Crohn's disease. Methods All patients who underwent an intestinal resection for Crohn's disease between 1995 and 2005 at Saint-Louis Hospital were retrospectively included. Time-to-clinical recurrence was compared in two groups: patients who had systematic ileocolonoscopy 6–12 months after intestinal surgery with tailored treatment according to the severity of endoscopic lesions (group C) and patients without systematic endoscopic evaluation (group NC). Results 132 patients (group C = 90, group NC = 42) were included. Probabilities of clinical recurrence were significantly lower in group C (21% and 26% at 3 and 5 years, respectively) compared with group NC (31% and 52% at 3 and 5 years respectively, p = 0.01). Conclusion Tailored treatment according to endoscopic assessment after ileocolonic resection is significantly associated with reduced clinical recurrence rate.

Upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) is rare and severe complications unusual. Stenosis has been reported, but gastroduodenal fistulae are seldom detected during surgery and most of the fistulae are cologastric or ileogastric. In complicated gastroduodenal CD, medical treatments are often effective and surgery is only considered in exceptional cases. We here report the unusual case of a 23-year-old patient with upper GI CD presenting a hyperalgic giant ulcer of the bulb fistulized in the pancreatic gland. The failure of steroids and two lines of combined treatment led us to a salvage surgical option. Abdominal exploration showed a plate stomach with an inflammatory bulboduodenal block. Cephalic duodenopancreatectomy and cholecystectomy were performed; histological analysis reported large fissuring pylorus ulceration with micro abscesses reaching the pancreas and the presence of non-caseating granulomas. Six months after the surgery, the patient had stopped antalgic treatment and did not have residual abdominal pain. He had gained 11 kg in weight and had no diarrhea with pancreatic enzymes. To our knowledge, we report the first case of an upper GI and fistulizing CD patient heavily treated with steroids and combined immunosuppressant agents requiring salvage cephalic duodenopancreatectomy.

3575 Background: BRAF mutations are present in 5-15% of mCRC. V600E BRAF mutations account for ~80% of cases and are mostly found in right-sided tumors. Non-V600E BRAF mutations are rare (~2% of mCRC), mostly left-sided. Although BRAF V600E mutations are associated with a dismal prognosis, some studies suggest that non-V600E BRAF mutations may be associated with a favorable outcome. The chemosensitivity of non-V600E BRAF-mutated mCRC has never been studied. Methods: From 2017 to 2018, all consecutive patients (pts) with non-V600E BRAF-mutated mCRC (next generation sequencing) treated in the participating centers were included. Survival analyses were performed using Kaplan-Meier method and LogRank test. Results: A total of 108 pts in 34 centers in France were included between October 2017 and August 2018 (median age, 66 years [range, 58-77]; ECOG performance status 0-1, 86%). The primary was mostly left-sided (66%). Main metastatic sites were the liver (73%), lungs (33%), lymph nodes (39%) and peritoneum (26%). D594 (34%), G469 (15%), K601 (11%), N581 (7%) and L597 (7%) were the most frequent mutations. A concomitant RAS mutation was found in 22% of pts. Microsatellite instability (MSI) was found in 3/67 pts (4.5%). First-line chemotherapy (CTx) (n = 69) efficacy was (overall response rate/disease control rate) 49%/77% (anti-EGFR-containing CTx [n = 20], 75%/85%; antiangiogenic-containing CTx [n = 22], 55%/73%). Median overall survival (mOS) was 25.6 months (95% CI : 17.1-43.8) overall; it was 8.0 months with best supportive care alone (n = 10), 16.0 months with palliative CTx alone (n = 63), and attained 105.1 months with curative-intent management of metastases (n = 35). mOS did not differ according to sidedness (p = 0.22), type of mutation (p = 0.52), or its functional impact on BRAF (p = 0.19). Conclusions: Non-V600E BRAF-mutated mCRC retain sensitivity to CTx + biologics and harbor a good prognosis (especially when amenable to curative-intent surgery), regardless of the type of mutation and its impact on BRAF kinase function. Contrarily to BRAF V600E mutations, non-V600E mutations may occur along with RAS mutations, but uncommonly with MSI.

The prognosis of peritoneal carcinomatosis (PC) from colorectal cancer has been improved with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, benefits of postoperative chemotherapy (CT) are unclear. This retrospective, multicenter study included 231 patients treated by CRS and HIPEC for isolated PC of colon cancer in four expert’s centers. Overall survival (OS), progression-free survival (PFS), and peritoneal recurrence-free survival (PRFS) were compared between patients with adjuvant CT (started within 3 months after surgery) and patients with surveillance only. After exclusion of 10 patients for early postoperative death (4 %), 221 patients were included (CT group: n = 151; surveillance group: n = 70). Main postoperative CT regimens (median of 6 cycles) were Folfox (28 %), Folfiri bevacizumab (24.5 %), Folfiri (16 %), and Folfiri cetuximab (12.5 %). The median OS after surgery was 43.3 months with no difference between CT and surveillance groups. In multivariate analysis, a low peritoneal cancer index (p

Colorectal cancers (CRC) develop in the face of an important immune system associated with the intestinal mucosal tissue. The immune response against the tumor has been proposed to affect the prognosis of patients undergoing treatment for CRC. In this study T cells infiltrating the tumor were compared with T cells populating the unaffected neighboring mucosal tissue and cells from the peripheral blood. We observed that T cells from the tumor harbor an activated phenotype, with engagement of the NKG2D pathway in CD8 T cells. We show that mucosal and tumor-infiltrating T cells are enriched in NKG2D CD4 T cells, which exhibit cytotoxic functions. Finally, T cell populations in the tumor were modified according to its oncogenetic status, with higher percentages of CD8 T cells isolated from patients with microsatellite instable tumor status.

Achalasia is a rare esophagus motility disorder. Medical, endoscopic and surgical treatments are available, but all endorse high relapse rates. No data has been published to date reporting a therapeutic effect of cannabis use neither in achalasia nor on its influence on manometric measurements. We report the case of a patient diagnosed with achalasia. He could benefit from a large panel of therapeutic interventions, but none of them was effective over the time. He first used cannabis at age 20 and identified benefits regarding achalasia symptoms. He maintained regular moderate cannabis use for 9 years, with minimal digestive inconvenience. A manometry performed without cannabis premedication was realized at age 26 and still found a cardiospasm. Cannabis use could explain the gap between functional symptoms assessment and manometry measurement. Further investigations are warranted to explore a therapeutic effect of cannabis in achalasia and possible influence on outcome measurements.

Background A KIT gain of function mutation is present in 70% of gastrointestinal stromal tumors (GISTs) and the wild-type (WT) allele is deleted in 5 to 15% of these cases. The WT KIT is probably deleted during GIST progression. We aimed to identify the mechanism of WT KIT loss and to determine whether other genes are involved or affected. Methods Whole-genome SNP array analyses were performed in 22 GISTs with KIT exon 11 mutations, including 11 with WT loss, to investigate the mechanisms of WT allele deletion. CGH arrays and FISH were performed in some cases. Common genetic events were identified by SNP data analysis. The 9p21.3 locus was studied by multiplex quantification of genomic DNA. Results Chromosome instability involving the whole chromosome/chromosome arm (whole C/CA) was detected in 21/22 cases. The GISTs segregated in two groups based on their chromosome number: polyGISTs had numerous whole C/CA gains (mean 23, range [9 to 43]/3.11 [1 to 5]), whereas biGISTs had fewer aberrations. Whole C/CA losses were also frequent and found in both groups. There were numerous copy-neutral losses of heterozygosity (cnLOH) of whole C/CA in both polyGIST (7/9) and biGIST (9/13) groups. cnLOH were frequent on 4q, 11p, 11q, 1p, 2q, 3p and 10, and never involved 12p, 12q, 20p, 20q or 19q. Other genetic alterations included segmental chromosome abnormalities, complete bi-allelic deletions (homozygous deletions) and, more rarely, amplifications. Nine of 11 GISTs with homozygous KIT exon 11 mutations had cnLOH of chromosome 4. Conclusion The cnLOH of whole C/CA is a frequent genetic alteration in GISTs and is closely associated with homozygous mutations of KIT and WT allele deletion. Electronic supplementary material The online version of this article (doi:10.1186/1476-4598-13-246) contains supplementary material, which is available to authorized users.

Neuroendocrine carcinomas (NEC) of the anus or the rectum are a rare disease, accounting for less than 1% of all digestive malignancies. Most are metastatic at diagnosis and treated with a platinum-based chemotherapy. No guidelines for localized tumors exist. The purpose of this study was to describe the characteristics of anorectal localized NEC, their management and their outcomes. We retrospectively reviewed patients from 11 French centers with anorectal localized NEC. We compared 2 therapeutic managements: surgery (group A) versus chemotherapy with or without radiation (group B). Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. A total of 24 patients were identified with a median follow-up of 25 months (3–60 months). Median age was 63 years old and 17 had a rectal tumor (71%). Mean Ki-67 was 72% (range: 20–100), and 75% of the tumors had a high proliferative index (Ki-67 > 50%). Global PFS and OS were 13.1 and 44.1 months, respectively. Thirty-seven percent of patients were in group A and 63% in group B. There was no difference between group A and group B, whether in terms of PFS (13.0 months vs. 13.2 months, P = 0.75) or OS (49.1 months vs. 39.2 months, P = 0.42). In patients with anorectal localized NEC, chemotherapy with or without radiation obtained a similar outcome as surgery and this conservative approach could be deemed a reasonable option.

10044 Background: Gain or loss of chromosome arms are frequently detected in gastrointestinal stromal tumors (GISTs), and have been correlated with outcome in some series. However, neither metaphas...