Publications by authors named "Christophe Locher"

34 Publications

Skeletal muscle loss during chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study.

Clin Res Hepatol Gastroenterol 2021 Mar 1;45(6):101603. Epub 2021 Mar 1.

Sorbonne Paris Cite, Paris Descartes University, Siric CARPEM, Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. Electronic address:

Purpose: We showed in a previous study that the PG-SGA score is associated with survival and chemotherapy-related toxicities in metastatic colorectal cancer (mCRC) patients. The objective was to evaluate the association between pretherapeutic sarcopenia and variation in skeletal muscle index (SMI) during treatment with these outcomes in the same population.

Methods: This prospective, multicenter, observational study enrolled non-pretreated mCRC patients. SMI was measured on routine CT scan at day 0 (D0) and day 60 (D60). Nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start.

Results: 149 patients were included from 7/2013 to 11/2016. Pretherapeutic sarcopenia was not significantly associated with survival or chemotherapy-related toxicities. The decrease in SMI > 14% was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95% CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.6, 95% CI 1.4-4.8, p = 0.002), independently of hypoalbuminemia and malnutrition defined by PG-SGA. Patients with a SMI decrease > 14% had a higher rate of grade ≥ 2 clinical toxicities (40% vs 22%, OR 3.0, 95% CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariable analysis.

Conclusion: To our knowledge, this is the first study to assess prospectively the association of skeletal muscle loss with survival and treatment toxicities in non-pretreated patients with mCRC. Pretherapeutic sarcopenia was not associated with poor outcomes, but the loss of skeletal muscle mass within 60 days from treatment start was highly prognostic, independently of other prognostic and nutritional factors.
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http://dx.doi.org/10.1016/j.clinre.2020.101603DOI Listing
March 2021

Prognostic factors of colorectal cancer patients with brain metastases.

Radiother Oncol 2021 Feb 16;158:67-73. Epub 2021 Feb 16.

Poitiers University, Poitiers, France; Department of Gastroenterology, Poitiers University Hospital, Poitiers, France. Electronic address:

Introduction: Brain metastases (BMs) from colorectal cancer (CRC) are rare (≈2%) but are increasing with the improvement of CRC prognosis. The main objective of this study was to evaluate the prognostic factors of BM from CRC.

Materials And Methods: This multicenter retrospective study included all consecutive patients with BM from CRC diagnosed between 2000 and 2017.

Theory/calculation: Prognostic factors of OS were evaluated in univariate (log-rank test) and multivariate analyses (Cox regression model). These prognostic factors could help the management of patients with BM from CRC.

Results: A total of 358 patients were included with a median age of 65.5 years. Primary tumors were mostly located in the rectum (42.4%) or left colon (37.2%) and frequently KRAS-mutated (56.9%). The median time from metastatic CRC diagnosis to BM diagnosis was 18.5 ± 2.5 months. BMs were predominantly single (56.9%) and only supratentorial (54.4%). BM resection was performed in 33.0% of the cases and 73.2% of patients had brain radiotherapy alone or after surgery. Median OS was 5.1 ± 0.3 months. In multivariate analysis, age under 65 years, ECOG performance status 0-1, single BM and less than 3 chemotherapy lines before BM diagnosis were associated with better OS. Prognostic scores, i.e. recursive partitioning analysis (RPA), Graded Prognostic Assessment (GPA), Disease Specific-Graded Prognostic Assessment (DS-GPA), Gastro-Intestinal-Graded Prognostic Assessment (GI-GPA) and the nomogram were statistically significantly associated with OS but the most relevant prognosis criteria seemed the ECOG performance status 0-1.

Conclusions: ECOG performance status, number of BM and number of chemotherapy lines are the most relevant factors in the management of patients with BM from CRC.
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http://dx.doi.org/10.1016/j.radonc.2021.02.006DOI Listing
February 2021

Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis.

Hepatol Int 2021 Feb 9;15(1):93-104. Epub 2021 Jan 9.

Centre Eugène Marquis, Rennes, France.

Background And Aims: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis.

Methods: PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS).

Results: 160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib.

Conclusion: In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib.

Clinical Trial Registration: The study was referenced in clinicaltrials.gov (NCT01357486).
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http://dx.doi.org/10.1007/s12072-020-10120-3DOI Listing
February 2021

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Department of Medical Oncology, Georges François Leclerc Cancer Center-UNICANCER, 1 rue Professeur Marion, 21000 Dijon, France.

Background: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan.

Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined.

Results: Baseline splenic volume > 180 mL was associated with poor PFS (median PFS = 9.2 versus 11.1 months; log-rank = 0.0125), but was not statistically associated with OS (median OS = 22.6 versus 28.5 months; log-rank = 0.1643). The increase in splenic volume at 3 months had no impact on PFS (HR 0.928; log-rank = 0.56) or on OS (HR 0.843; log-rank = 0.21). Baseline splenic volume was positively correlated with the level of baseline circulating mMDSC ( = 0.48, -value = 0.031).

Conclusion: Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation.
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http://dx.doi.org/10.3390/cancers12061429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352427PMC
May 2020

Reasons for chemotherapy discontinuation and end-of-life in patients with gastrointestinal cancer: A multicenter prospective AGEO study.

Clin Res Hepatol Gastroenterol 2021 Jan 11;45(1):101431. Epub 2020 May 11.

Department of hepatogastroenterology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75013 Paris, France.

Background: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.

Methods: This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.

Results: One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.

Conclusion: Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
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http://dx.doi.org/10.1016/j.clinre.2020.03.029DOI Listing
January 2021

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study.

Int J Cancer 2020 07 13;147(1):285-296. Epub 2020 Feb 13.

Sorbonne University and Medical Oncology Department, Saint Antoine Hospital, Paris, France.

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.
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http://dx.doi.org/10.1002/ijc.32879DOI Listing
July 2020

Efficacy and Safety of Aflibercept in Combination With Chemotherapy Beyond Second-Line Therapy in Metastatic Colorectal Carcinoma Patients: An AGEO Multicenter Study.

Clin Colorectal Cancer 2020 03 4;19(1):39-47.e5. Epub 2019 Sep 4.

Department of Digestive Oncology, European Georges Pompidou Hospital, René Descartes University, Paris, France. Electronic address:

Background: Although no data have been reported beyond second-line therapy, aflibercept is approved in this setting in many countries. We conducted a multicenter study to analyze the efficacy and safety of a aflibercept-chemotherapy regimen beyond second-line therapy in patients with metastatic colorectal cancer.

Patients And Methods: Metastatic colorectal cancer patients treated with aflibercept beyond second-line therapy were included. Objective response rate, overall survival (OS), and progression-free survival (PFS) were assessed.

Results: A total of 130 patients were included. Median OS and PFS were 7.6 months (95% confidence interval, 6.2-9.3) and 3.3 months (95% confidence interval, 2.7-3.8), respectively. The best response rates were partial response 6.9%, stable disease 38.5%, progressive disease 42.5%, and not evaluable 12%. According to whether patients received previous FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin)-bevacizumab or not, OS was 7.7 and 8.1 months (P = .31), and PFS was 2.9 and 3.9 months (P = .02), respectively. Interestingly, PFS and OS were both significantly improved by 4% and 5% per month, respectively, without antiangiogenic treatment before the initiation of the aflibercept regimen. The negative effect of prior FOLFIRI-bevacizumab or shorter time since last bevacizumab was maintained in multivariate analysis for both OS and PFS.

Conclusion: The aflibercept-chemotherapy regimen is a therapeutic option in patients with chemorefractory disease beyond second-line therapy, in particular in patients with an antiangiogenic-free interval.
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http://dx.doi.org/10.1016/j.clcc.2019.08.003DOI Listing
March 2020

Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.

Clin Res Hepatol Gastroenterol 2020 06 10;44(3):295-301. Epub 2019 Oct 10.

Department of Gastroenterology and Digestive Oncology, Georges-Pompidou European Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Sorbonne Paris Cité Paris Descartes University, Paris, France.

Background: 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.

Methods: 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.

Results: 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, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.clinre.2019.08.009DOI Listing
June 2020

Folfirinox gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study.

Therap Adv Gastroenterol 2019 25;12:1756284819878660. Epub 2019 Sep 25.

Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.

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 ( = 107) or GN ( = 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 ( = 0.008) and after ( = 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;  = 0.053). After matching ( = 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;  = 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%;  = 0.01), which suggests a higher feasibility for the FFX-GN sequence. Corresponding median OS were 19 months 9.5 months, respectively ( = 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.
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http://dx.doi.org/10.1177/1756284819878660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764033PMC
September 2019

Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study.

Eur J Cancer 2019 09 12;119:35-43. Epub 2019 Aug 12.

Sorbonne Paris Cite, Paris Descartes University, Siric CARPEM, Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France. Electronic address:

Introduction: The Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC).

Objective: The objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non-pre-treated patients with mCRC.

Methods: This prospective multicentre observational study enrolled non-pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment.

Results: A total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7-8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3-5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8-2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters.

Conclusion: Although more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.
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http://dx.doi.org/10.1016/j.ejca.2019.07.011DOI Listing
September 2019

Increased incidence of Campylobacter enteritis and their quinolone resistance between 2010 and 2015: Results of a French national observatory conducted in 21 general hospitals (CHG).

Clin Res Hepatol Gastroenterol 2019 06 7;43(3):338-345. Epub 2018 Dec 7.

Centre hospitalier de Marne la Vallée, 2-4 cours de la Gondoire, 77600 Jossigny, France. Electronic address:

Introduction: In Europe, the number of cases of Campylobacter enteritis and their quinolone resistance is increasing. The aims of this work were to evaluate: (1) the hospital epidemiology of bacterial enteritis between 2010 and 2015. (2) The proportion of Campylobacter and Salmonella enteritis. (3) Resistance to quinolones in adult and paediatric populations. (4) To investigate possible regional epidemiological and bacteriological disparities.

Patients And Methods: This is a multicentric study carried out in 21 general hospitals (CHG) representing 14 French regions with a prospective collection of the results of coprocultures from 2010 to 2015 in adult and paediatric populations (children < 15 years old not exposed to quinolones). The epidemiological and bacteriological data were collected from software laboratory for positive stool cultures for Campylobacter and Salmonella. The results were compared year by year and by a period of 2 years.

Results: In adults, Campylobacter enteritis was each year significantly more frequent than Salmonella (P < 0.001), with a significant increase from 2010 to 2015 (P < 0.05). In children, there was also a significant and stable predominance of Campylobacter enteritis over the study period (P = 0.002). The quinolone resistance of Campylobacter was greater than 50% on the whole territory, with no North-South difference over the three periods studied. It increased significantly from 2012 to 2015 in adults (48% to 55%, P < 0.05) and in children (54% to 61%, P = 0.04).

Conclusion: Our results confirm the increase in the prevalence of Campylobacter enteritis compared to Salmonella between 2010 and 2015. The quinolone resistance of Campylobacter is greater than 50% on the whole territory, stable between 2010 and 2015 in adults and significantly increased in children.
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http://dx.doi.org/10.1016/j.clinre.2018.10.015DOI Listing
June 2019

Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO).

Dig Liver Dis 2018 Jan 6;50(1):15-19. Epub 2017 Oct 6.

CHU de Reims, Reims Cedex, France.

Background: This document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016.

Method: This collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009).

Results: Small bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement).

Conclusion: Few specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.
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http://dx.doi.org/10.1016/j.dld.2017.09.123DOI Listing
January 2018

Over 90% of cases of Microscopic Colitis can be diagnosed by performing a short colonoscopy.

Clin Res Hepatol Gastroenterol 2017 Jun 16;41(3):333-340. Epub 2017 Feb 16.

Montfermeil, France.

Aims: To determinate the topographical distribution of key diagnostic histological features of lymphocytic colitis (LC) and collagenous colitis (CC) and to establish what correlations may exist between the histological findings and the causes and severity of MC.

Patients And Methods: Patients with MC were included in a prospective multicentre French study from September 2010 to October 2012. MC was diagnosed by performing total colonoscopy with multiple biopsies of the rectum and colon collected in separate jars and analyzed separately for each site (descending and sigmoid colon, transverse colon, ascending colon). CC was defined as a subepithelial collagen layer>10μm thick and LC as an intraepithelial lymphocyte (IEL) count>20 lymphocytes per 100 epithelial cells without any associated thickening of the subepithelial collagen.

Results: Ninety-five patients, 69 with LC 26 and with CC, were included in the analysis. The sensitivity of the biopsies for diagnosing MC was maximum in the transverse colon and minimum in the rectum. Rectal and left colonic biopsies resulted in the diagnosis of CC and CL in 93% and 94% of cases, respectively. All the remaining cases of MC were diagnosed by performing additional biopsies beyond the splenic flexure. In patients with LC, a higher rate of IELs was associated with the absence of abdominal pain (P=0.01) and a shorter duration of diarrhea (P=0.001). In patients with CC, a lower level of collagen thickness in the basement membrane was associated with the presence of an autoimmune disease (P=0.02).

Conclusion: More than 90% of cases of microscopic colitis were diagnosed in this study by performing rectal and left colonic biopsies.
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http://dx.doi.org/10.1016/j.clinre.2016.12.008DOI Listing
June 2017

Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients.

Eur J Cancer 2017 03 5;74:98-108. Epub 2016 Nov 5.

CHU Le Bocage and INSERM U866 Dijon, France. Electronic address:

Aim: Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis.

Method: Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results: From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL.

Conclusion: The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.
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http://dx.doi.org/10.1016/j.ejca.2016.09.029DOI Listing
March 2017

Perioperative chemotherapy with FOLFOX in resectable gastroesophageal adenocarcinoma in real life practice: An AGEO multicenter retrospective study.

Dig Liver Dis 2016 Dec 9;48(12):1498-1502. Epub 2016 Aug 9.

Gastroenterology and Digestive Oncology Department, Avicenne Hospital, APHP and Université Paris 13, Sorbonne Paris Cité, Bobigny, France.

Purpose: Perioperative chemotherapy with 5-fluorouracil and cisplatin, with or without epirubicin, improves overall survival in resectable gastroesophageal junction and gastric adenocarcinoma. The aim of this retrospective multicenter study was to evaluate the safety and efficacy of perioperative chemotherapy with a FOLFOX-based regimen.

Patients And Methods: We enrolled patients with resectable gastric or gastroesophageal adenocarcinoma, who had at least 3 cycles of a pre-operative FOLFOX-based regimen. The primary end point was the feasibility of the peri-operative chemotherapy.

Results: We enrolled 109 patients from 2007 to 2012 in 12 centres. Their median age was 66, 67% were men and 73% had gastric tumours. The median number of chemotherapy courses was 6 with a median of 4 pre-operative cycles and 2 post-operative cycles. Twenty-three patients received at least 8 cycles of chemotherapy. In univariate analysis, the Karnofsky index at inclusion was the only factor associated with 8 cycles of chemotherapy. An R0 resection was achieved in 100 patients (95.2%).

Conclusion: The FOLFOX-based perioperative regimen achieves favourable results in real life practice. The optimal number of chemotherapy cycle remains to be determined. FOLFOX regimen may be used as an alternative treatment option to a cisplatin-based regimen in resectable gastroesophageal adenocarcinoma. A prospective randomized trial is needed to confirm these results.
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http://dx.doi.org/10.1016/j.dld.2016.07.022DOI Listing
December 2016

Safety and efficacy of palliative systemic chemotherapy combined with colorectal self-expandable metallic stents in advanced colorectal cancer: A multicenter study.

Clin Res Hepatol Gastroenterol 2016 Apr 21;40(2):230-8. Epub 2015 Oct 21.

François Rabelais University, Tours, France; Department of Hepatogastroenterology and Digestive Oncology, University Hospital of Tours, Tours, France. Electronic address:

Purpose: Self-expandable metallic stent (SEMS) placement is an accepted palliative therapy for management of acute malignant bowel obstruction in advanced colorectal cancer. Nevertheless, data are lacking on the effects of systemic chemotherapy combined with colorectal SEMS. The aim of this study was to investigate the safety and efficacy of palliative chemotherapy for advanced colorectal cancer combined with colorectal SEMS placement.

Patients And Methods: This multicentre retrospective study included all consecutive advanced colorectal cancer patients who received first-line palliative chemotherapy combined with endoscopic stenting for colorectal cancer with obstruction. We analyzed the number of cycles and the type of combination used. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, response rate, grade 3-4 toxicity and the outcomes of SEMS for malignant colorectal obstruction.

Results: A total of 38 patients were included. Among them, 25 patients received oxaliplatin and 5-fluorouracil combination chemotherapy. Objective response and stabilization occurred in 38 and 24% of patients, respectively. The median overall survival and progression-free survival from the start of chemotherapy were 18 and 5months, respectively. The objective response rate and overall disease control rate were 38 and 62%, respectively. Toxicity was generally acceptable. Major complications related to stenting included perforation (8%), stent migration (5%), and reobstruction secondary to tumor ingrowths (13%).

Conclusions: Chemotherapy combined with colonic stenting as a first-line treatment seems to be a valid option in advanced colorectal cancer patients with malignant colorectal obstruction.
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http://dx.doi.org/10.1016/j.clinre.2015.09.004DOI Listing
April 2016

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

Br J Cancer 2015 Sep 15;113(7):989-95. Epub 2015 Sep 15.

Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Descartes University, Paris, France.

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.
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http://dx.doi.org/10.1038/bjc.2015.328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651133PMC
September 2015

Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset.

Authors:
Josef Thaler Richard Greil Johannes Gaenzer Wolfgang Eisterer Joerg Tschmelitsch Hellmut Samonigg August Zabernigg Franz Schmid Günther Steger Robert Steinacher Johannes Andel Alois Lang Reinhold Függer Friedrich Hofbauer Ewald Woell Dietmar Geissler Alfred Lenauer Manfred Prager Jean-Luc Van Laethem Eric Van Cutsem Geert D'Haens Gauthier Demolin Joseph Kerger Guido Deboever Gilbert Ghillebert Marc Polus Eric Van Cutsem Hassan RezaieKalantari Thierry Delaunoit Jean Charles Goeminne Marc Peeters Philippe Vergauwe Ghislain Houbiers Yves Humblet Jos Janssens Dirk Schrijvers Erik Vanderstraeten Jean-Luc Van Laethem Jan Vermorken Daniel Van Daele Michel Ferrante Frederic Forget Alain Hendlisz Mette Yilmaz Svend Erik Nielsen Lene Vestermark Jim Larsen Marc Ychou Ayman Zawadi Mohamed-Ayman Zawadi Olivier Bouche Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou Eveline Boucher Julien Taieb Denis Pezet Francoise Desseigne Michel Ducreux Patrick Texereau Laurent Miglianico Philippe Rougier Serge Fratte Charles-Briac Levache Yacine Merrouche Stephen Ellis Christophe Locher Jean-Francois Ramee Claire Garnier Frederic Viret Bruno Chauffert Isabelle Cojean-Zelek Pierre Michel Cedric Lecaille Christian Borel Jean-Francois Seitz Denis Smith Catherine Lombard-Bohas Thierry Andre Jean-Marc Gornet Francine Fein Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky Jean-Paul Lagasse Dominique Luet Pierre-Luc Etienne Mohamed Gasmi Andre Vanoli Suzanne Nguyen Thomas Aparicio Hervé Perrier Noel Stremsdoerfer Philippe Laplaige Dominique Arsene Dominique Auby Laurent Bedenne Romain Coriat Bernard Denis Patrick Geoffroy Gilles Piot Yves Becouarn Gilbert Bordes Gael Deplanque Olivier Dupuis Frederic Fruge Rosine Guimbaud Thierry Lecomte Gérard Lledo Iradej Sobhani Amani Asnacios Ahmed Azzedine Christophe Desauw Marie-Pierre Galais Dany Gargot You-Heng Lam Abakar Abakar-Mahamat Jean-Francois Berdah Sylviane Catteau Marie-Christine Clavero-Fabri Jean-Francois Codoul Jean-Louis Legoux Denis Goldfain Pierre Guichard Denis Pere Verge Jocelyne Provencal Bruno Vedrenne Catherine Brezault-Bonnet Denis Cleau Jean-Paul Desir David Fallik Bruno Garcia Marie-Hélène Gaspard Dominique Genet Johannes Hartwig Yves Krummel Tamara MatysiakBudnik Vanessa Palascak-Juif Harizo Randrianarivelo Yves Rinaldi Albert Aleba Ariane Darut-Jouve Aimery de Gramont Herve Hamon Frederic Wendehenne Axel Matzdorff Michael Konrad Stahl Wolfgang Schepp Martin Burk Lothar Mueller Gunnar Folprecht Michael Geissler Luisa Mantovani-Loeffler Thomas Hoehler Walter Asperger Hendrik Kroening Ludwig Fischer von Weikersthal Stefan Fuxius Matthias Groschek Johannes Meiler Tanja Trarbach Jacqueline Rauh Nicolas Ziegenhagen Albrecht Kretzschmar Ullrich Graeven Arnd Nusch Goetz von Wichert Ralf-Dieter Hofheinz Gerhard Kleber Karl-Heinz Schmidt Ursula Vehling-Kaiser Claudia Baum Jochen Schuette Georg Martin Haag Wilhelm Holtkamp Jochen Potenberg Tobias Reiber Georg Schliesser Hans-Joachim Schmoll Wolfgang Schneider-Kappus Wolfgang Abenhardt Claudio Denzlinger Jan Henning Bartscht Marxsen Hans GuenterDerigs Helmut Lambertz Ingulf Becker-Boost Karel Caca Christian Constantin Thomas Decker Henning Eschenburg Sigrun Gabius Holger Hebart Albrecht Hoffmeister Heinz-August Horst Stephan Kremers Malte Leithaeuser Sebastian Mueller Siegfried Wagner Severin Daum Frank Schlegel Martina Stauch Volker Heinemann Roberto Labianca Giuseppe Colucci Dino Amadori Enrico Mini Alfredo Falcone Corrado Boni Evaristo Maiello Luciano Latini Alberto Zaniboni Dino Amadori Giuseppe Aprile Sandro Barni Rodolfo Mattioli Andrea Martoni Rodolfo Passalacqua Mario Nicolini Enzo Pasquini Carla Rabbi Enrico Aitini Alberto Ravaioli Carlo Barone Guido Biasco Stefano Tamberi Angelo Gambi Claudio Verusio Marina Marzola Giorgio Lelli Corrado Boni Stefano Cascinu Paolo Bidoli Massimo Vaghi Giorgio Cruciani Francesco Di Costanzo Alberto Sobrero Enrico Mini Roberto Petrioli Massimo Aglietta Oscar Alabiso Federico Capuzzo Alfredo Falcone Domenico Cristi Corsi Roberto Labianca Stefania Salvagni Silvana Chiara Francesco Ferraù Francesco Giuliani Sara Lonardi Nicola Gebbia Giovanni Mantovani Evaristo Sanches Evaristo Sanches Juan Carlos Mellidez Pedro Santos Joao Freire Cristina Sarmento Luis Costa Antonio Moreira Pinto Sergio Barroso Jorge Espirito Santo Fátima Guedes Amélia Monteiro Anabela Sa Irene Furtado Josep Tabernero Ramon Salazar Enrique Aranda Aguilar Fernando Rivera Herrero Josep Tabernero Javier Sastre Valera Manuel ValladaresAyerbes Jaime FeliuBatlle Silvia Gil Carlos Garcia-Giron Guillermo Lopez Vivanco Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia Javier Gallego Bartomeu Massuti Sureda Jordi Remon Maria Jose Safont Aguilera Luis CireraNogueras BernadoQueralt Merino Cristina Gravalos Castro Purificacion Martinez de Prado Carlos PijaumePericay Manuel ConstenlaFigueiras InmaculadaGuasch Jordan Maria Jose GomeReina Amelia Lopez-Ladron Garcia Antonio Arrivi Garcia-Ramos Andres Cervantes Carlos Fernandez Martos Eugenio MarcuelloGaspar Ines Cabezas Montero Pilar Escudero Emperador Ana Leon Carbonero Manuel Gallen Castillo Teresa Garcia Garcia Jose Garcia Lopez Encarnacion Gonzalez Flores Monica GuillotMorales Marta LlanosMuñoz Ana López Martín Joan Maurel Juan Carlos Camara Rosario Dueñas Garcia Mercedes Salgado Isabel HernandezBusquier Teresa Checa Ruiz Adelaida LacastaMuñoa MiquelNogue Aliguer Amalia Velasco Ortiz de Taranco Miguel Mendez Ureña Ferran Losa Gaspa Jose Juan Ponce Carlos Bosch Roig Pedro Valero Jimenez Antonio GalanBrotons Santiago AlbiolRodriguez Jose Ales Martinez Liliana Canosa Ruiz Margarita CentellesRuiz John Bridgewater Rob Glynne-Jones Saad Tahir Tamas Hickish Jim Cassidy Leslie Samuel

Ann Oncol 2015 Apr;26(4):822-825

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http://dx.doi.org/10.1093/annonc/mdv070DOI Listing
April 2015

Microscopic colitis or functional bowel disease with diarrhea: a French prospective multicenter study.

Am J Gastroenterol 2014 Sep 8;109(9):1461-70. Epub 2014 Jul 8.

1] Service de Gastro-Entérologie, Centre Hospitalier Intercommunal Le Raincy-Montfermeil, Montfermeil, France [2] These authors contributed equally to this work [3] Full investigators are listed before study highlights.

Objectives: To describe the characteristics of a cohort of patients with microscopic colitis (MC; lymphocytic (LC) or collagenous (CC) colitis) and to compare them with patients with functional bowel disorder with diarrhea (FBD-D).

Methods: Between September 2010 and June 2012, patients fulfilling the following inclusion criteria were prospectively included in 26 centers in France: (i) having at least three bowel movements daily with change in stool consistency; (ii) duration of abnormal bowel habit >4 weeks; and (iii) normal or near-normal colonoscopy. Each patient underwent a colonoscopy and colonic biopsies. We compared the demographic, clinical, biological, and etiological characteristic of patients with MC (CC and LC) with those of control patients with FBD-D.

Results: A total of 433 patients were included: 129 with MC (87 LC and 42 CC), 23 with another organic disease, and 278 with FDB-D, including patients with diarrhea and abdominal pain who met the criteria of Rome III (irritable bowel syndrome with diarrhea) and patients with functional diarrhea without abdominal pain. Logistic regression analysis identified the following independent predictors of MC: age >50 years (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.6-5.9), presence of nocturnal stools (OR=2, 95% CI=1.1-3.9), weight loss (OR=2.5, 95% CI=1.3-4.7), duration of diarrhea <12 months (OR=2.0, 95% CI=1.1-3.5), recent introduction of new drugs (OR=3.7, 95% CI=2.1-6.6; P<0.0001), and the presence of a known autoimmune disorder (OR=5.5, 95% CI=2.5-12).

Conclusions: Age >50 years, the presence of nocturnal stools, weight loss, the introduction of a new drug, and the presence of a known autoimmune disease increase the probability of MC and thus the indication for colonoscopy with biopsies.
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http://dx.doi.org/10.1038/ajg.2014.182DOI Listing
September 2014

Prospective study of Hepatitis E Virus infection among pregnant women in France.

Virol J 2014 Apr 9;11:68. Epub 2014 Apr 9.

AP-HP, Hôpital Paul Brousse, Virologie, Villejuif 94804, France.

Background: Hepatitis E Virus (HEV) infection has a poor prognosis among pregnant women from high endemic countries. HEV-prevalence and incidence among pregnant women is unknown in high-income countries such as France. This prospective study was conducted to assess HEV infection in this setting.

Findings: An overall HEV prevalence of 7.74% was observed among 315 pregnant women. Seroprevalence was higher in south than in north of France (29.3% vs. 3.6%, p < 0.0001), and women with detectable IgG were older. No IgG seroconversion or IgM detection were observed during pregnancy.

Conclusions: Data suggest that HEV infection is a rare occurrence during pregnancy even in regions of western countries with high seroprevalence rates.
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http://dx.doi.org/10.1186/1743-422X-11-68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011159PMC
April 2014

Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment.

Dig Liver Dis 2014 Feb 21;46(2):97-104. Epub 2013 Jun 21.

Oncology Unit, Saint Antoine Hospital, APHP, Paris, France.

Small bowel adenocarcinomas are rare tumours, but their incidence is increasing. Their most common primary location is the duodenum. The few studies that have collected data regarding small bowel adenocarcinoma are not homogeneous and are widely spread over time. Even though these tumours are most often sporadic, some predisposing diseases have been identified, among which Crohn's disease and genetic syndromes. Early diagnosis of small bowel adenocarcinoma remains difficult despite significant radiological and endoscopic progress. After surgical resection the main prognostic factor is node invasion; in this case, adjuvant chemotherapy can be expected to be beneficial, although this has not been established by randomised trials. For metastatic disease, platinum-based chemotherapy seems to be the most effective treatment. Targeted therapies have not yet been evaluated in this type of cancer.
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http://dx.doi.org/10.1016/j.dld.2013.04.013DOI Listing
February 2014

Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients.

J Clin Oncol 2013 Apr 4;31(11):1464-70. Epub 2013 Mar 4.

Gastroenterology, Avicenne Hospital, AP-HP, Université Paris 13, Sorbonne Paris Cité, 125 rue de Stalingrad, 93000 Bobigny, France.

Purpose: Elderly patients form a heterogeneous population. Evaluation of geriatric factors may help evaluate a patient's health status to better adapt treatment.

Patients And Methods: Elderly patients with previously untreated metastatic colorectal cancer (mCRC) were randomly assigned to receive fluorouracil (FU) -based chemotherapy either alone or in combination with irinotecan (IRI) in the Fédération Francophone de Cancérologie Digestive (FFCD) 2001-02 study. Sites participating in the geriatric substudy completed geriatric screening tools to perform prognostic factor analyses for treatment safety during the first 4 months after treatment initiation.

Results: The geriatric score was calculated in 123 patients (44%). Median age was 80 years (range, 75 to 91 years). The Charlson comorbidity index was ≤ 1 in 75%, Mini-Mental State Examination (MMSE) score was ≤ 27/30 in 31%, and Instrumental Activities of Daily Living (IADL) showed impairment in 34% of the patients. Seventy-one patients (58%) had grade 3 to 4 toxicity, 41 (33%) had a dose-intensity reduction of more than 33%, and 54 (44%) had at least one unexpected hospitalization during the first 4 months after starting treatment. In multivariate analysis, significant predictive factors for grade 3-4 toxicity were IRI arm (odds ratio [OR], 5.03), MMSE ≤ 27/30 (OR, 3.84), and impaired IADL (OR, 4.67); for dose-intensity reduction of > 33%, the significant predictive factors were alkaline phosphates > 2 × upper limit of normal (OR, 4.16) and IRI arm (OR, 6.85); and for unexpected hospitalization, significant predictive factors were MMSE ≤ 27/30 (OR, 4.56) and Geriatric Depression Scale ≤ 2 (OR, 5.52).

Conclusion: Geriatric factors (MMSE and IADL) are predictive of severe toxicity or unexpected hospitalization (MMSE) in a randomized prospective phase III study in mCRC. These results suggest that cognitive function and autonomy impairment should be taken into account when choosing a regimen for chemotherapy.
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http://dx.doi.org/10.1200/JCO.2012.42.9894DOI Listing
April 2013

Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study.

Oncology 2011 20;81(5-6):395-402. Epub 2012 Jan 20.

Service de gastro-entérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, Faculté Paris Descartes, France.

Background: The possible impact of malnutrition on the tolerability and efficacy of modern chemotherapy regimens for metastatic colorectal cancer (mCRC) is unclear.

Methods: In this prospective, cross-sectional, multicenter study, we collected demographic, oncological and nutritional data for all consecutive mCRC patients during a 14-day period in eight hospitals. Nutritional status was assessed with the nutritional risk index (NRI), and patients were classified as severely malnourished when NRI was <83.5; drug-induced toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Survival times were calculated from the date of the nutritional assessment.

Results: We enrolled 114 mCRC patients (median age: 65 years, range: 22-92; WHO performance status 0/1/2/3: 21/54/21/4%) of whom 88% had at least 2 metastatic sites and 49% were receiving chemotherapy as first-line treatment. Malnutrition was diagnosed in 65% of the patients and was severe in 19%. Severe malnutrition was associated with more adverse effects following chemotherapy (p = 0.01) and with shorter median overall survival (14.0 vs. 36.2 months in non-/moderately malnourished patients, p = 0.02).

Conclusions: In mCRC patients, severe malnutrition is associated with greater chemotherapy toxicity and reduced overall survival.
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http://dx.doi.org/10.1159/000335478DOI Listing
June 2012

Second-line chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) in patients with advanced small bowel adenocarcinoma after failure of first-line platinum-based chemotherapy: a multicenter AGEO study.

Cancer 2011 Apr 8;117(7):1422-8. Epub 2010 Nov 8.

Medical Oncology Service, Hospital Saint Antoine, AP-HP, University of Paris VI, Paris, France.

Background: Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. First-line platinum-based chemotherapy is active in patients with advanced SBA, but data regarding second-line chemotherapy are lacking. The aim of this study was to evaluate the efficacy and tolerability of fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) as second-line chemotherapy in patients with advanced SBA.

Methods: We analyzed all consecutive patients who received second-line chemotherapy with FOLFIRI among 93 patients with advanced SBA included from 1996 to 2008 in a previous retrospective multicenter study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method. Cox models were applied for multivariate analyses.

Results: Among 51 patients who received second-line chemotherapy, 28 patients (male, 57%; median age, 54 years; metastatic disease, 96%) were treated with FOLFIRI after progression (n = 24) or limiting toxicity (n = 4) to first-line FOLFOX (n = 19) or LV5FU2-cisplatin (n = 9). Grade 3-4 toxicity was observed in 48% of patients (grade 3-4 neutropenia, 37%). After a median follow-up of 21.5 months, all patients had tumor progression, and 22 patients died. Objective response rate was 20%, and disease control rate was 52%. Median PFS and OS were 3.2 and 10.5 months, respectively. No clinical, biological, or tumor characteristics were associated with PFS or OS by multivariate analysis.

Conclusions: Second-line chemotherapy with FOLFIRI produced disease control in half of patients with advanced SBA after failure with first-line platinum-based chemotherapy. Nevertheless, the short median PFS warrants the evaluation of other treatments including targeted therapies.
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http://dx.doi.org/10.1002/cncr.25614DOI Listing
April 2011

Esophageal tuberculosis in a patient on maintenance dialysis: advantages of interferon-gamma release assay.

Ren Fail 2009 ;31(3):248-50

Department of Nephrology, Meaux General Hospital, Meaux, France.

Patients with chronic renal failure have a higher risk of developing tuberculosis compared to the general population, and especially extra-pulmonary tuberculosis. This pathology is often difficult to diagnose and requires a combination of multidisciplinary examinations. The confirmation of the diagnosis is important in order to quickly match the treatment with the pathology. We report a patient with primary esophageal tuberculosis for whom the interferon gamma release assay facilitated a timely diagnosis.
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http://dx.doi.org/10.1080/08860220802709754DOI Listing
May 2009

Socioeconomic deprivation does not influence the severity of Crohn's disease: Results of a prospective multicenter study.

Inflamm Bowel Dis 2009 Apr;15(4):594-8

Hôpital de Montfermeil, France.

Background: Socioeconomic deprivation is associated with poor health. The aims of this study were to evaluate the influence of deprivation in the characteristics and comparisons of deprived and nondeprived Crohn's disease (CD) patients.

Methods: CD patients were prospectively recruited from September 2006 to June 2007 in 6 hospitals in the Paris area. To assess the level of deprivation we used the EPICES score (Evaluation of Precarity and Inequalities in Health Examination Centers; http://www.cetaf.asso.fr), a validated individual index of deprivation developed in France, a score >30 defining deprivation. We defined CD as severe when at least 1 of the conventionally predefined criteria of clinical severity was present.

Results: In all, 207 patients (128 women and 79 men, mean age 40 years) were included and had a median score of deprivation of 20.7 (0-100). Seventy-three (35%) were deprived. There were no statistical differences between deprived and nondeprived patients for the following parameters: 1) mean age: 39 +/- 14.6 versus 40.6 +/- 13.5, P = 0.4; 2) sex ratio (female/male): 87/47 (65%) versus 41/32 (56%), P = 0.2; 3) duration of disease (years) 9 +/- 8.8 versus 8.5 +/- 7.2, P = 0.7; 4) delay from onset of symptoms to diagnosis >1 year: 22/115 (19%) versus 13/63 (21%), P = 0.8; and 5) severity of disease 71% versus 70% (P = 0.9). Nondeprived patients had a lower rate of hospitalization (40 versus 56%, P = 0,04) and a higher rate of surgery (44 versus 22%, P = 0,004); the rate of surgery was only identified by logistic regression.

Conclusions: In this study deprivation does not seem to influence the severity of CD. This can be explained by easy access to healthcare in France.
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http://dx.doi.org/10.1002/ibd.20794DOI Listing
April 2009

Fixed-dose rate gemcitabine in elderly patients with advanced pancreatic cancer: an observational study.

Crit Rev Oncol Hematol 2008 Nov 30;68(2):178-82. Epub 2008 Jul 30.

Department of Gastro-enterology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.

Pancreatic cancer represents one of the most lethal cancers and treatment of advanced disease remains palliative. Age-related physiologic changes can increase chemotherapy's toxicity but the use of gemcitabine in elderly patients has not been properly evaluated. This observational prospective study evaluated patients aged 70 years and over, receiving gemcitabine for an advanced pancreatic carcinoma. Gemcitabine was delivered according to the usual fixed-dose rate schedule (1000mg/(m(2)week) over 100min, every week, 3 weeks over 4). Thirty-nine patients (median age 74) were treated between November 1999 and August 2004. Twenty-three patients (59%) received 100% of the planned dose-intensity. Grade 3-4 toxicities were neutropenia (38% of patients), thrombocytopenia (28%), anemia (18%) and alopecia (18%). Four partial responses (10%) and 13 stabilizations (33%) were observed. Eight patients (20%) experienced clinical benefit. The median progression free and overall survivals were 7 and 10 months, respectively. Gemcitabine can be administered in selected elderly patients.
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http://dx.doi.org/10.1016/j.critrevonc.2008.06.010DOI Listing
November 2008