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1. Microsatellite instability at U2AF-binding polypyrimidic tract sites perturbs alternative splicing during colorectal cancer initiation

Author

Vincent Jonchère, Hugo Montémont, Enora Le Scanf, Aurélie Siret, Quentin Letourneur, Emmanuel Tubacher, Christophe Battail, Assane Fall, Karim Labreche, Victor Renault, Toky Ratovomanana, Olivier Buhard, Ariane Jolly, Philippe Le Rouzic, Cody Feys, Emmanuelle Despras, Habib Zouali, Rémy Nicolle, Pascale Cervera, Magali Svrcek, Pierre Bourgoin, Hélène Blanché, Anne Boland, Jérémie Lefèvre, Yann Parc, Mehdi Touat, Franck Bielle, Danielle Arzur, Gwennina Cueff, Catherine Le Jossic-Corcos, Gaël Quéré, Gwendal Dujardin, Marc Blondel, Cédric Le Maréchal, Romain Cohen, Thierry André, Florence Coulet, Pierre de la Grange, Aurélien de Reyniès, Jean-François Fléjou, Florence Renaud, Agusti Alentorn, Laurent Corcos, Jean-François Deleuze, Ada Collura, and Alex Duval

Subjects
Colorectal cancer, Mismatch repair deficiency, Microsatellite instability, Whole-exome and RNA sequencing, Alternative splicing, Polypyrimidine U2AF binding site, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the different steps of colorectal tumorigenesis using whole exome sequencing and search for associated splicing events via RNA sequencing at the bulk-tumor and single-cell levels. Results Our results demonstrate that MSI leads to hundreds of noncoding DNA mutations, notably at polypyrimidine U2AF RNA-binding sites which are endowed with cis-activity in splicing, while higher frequency of exon skipping events are observed in the mRNAs of MSI compared to non-MSI CRC. At the DNA level, these noncoding MSI mutations occur very early prior to cell transformation in the dMMR colonic crypt, accounting for only a fraction of the exon skipping in MSI CRC. At the RNA level, the aberrant exon skipping signature is likely to impair colonic cell differentiation in MSI CRC affecting the expression of alternative exons encoding protein isoforms governing cell fate, while also targeting constitutive exons, making dMMR cells immunogenic in early stage before the onset of coding mutations. This signature is characterized by its similarity to the oncogenic U2AF1-S34F splicing mutation observed in several other non-MSI cancer. Conclusions Overall, these findings provide evidence that a very early RNA splicing signature partly driven by MSI impairs cell differentiation and promotes MSI CRC initiation, far before coding mutations which accumulate later during MSI tumorigenesis.

Published
2024
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2. What defines a great surgeon? A survey study confronting perspectives

Author

Romain Luscan, Emeline Malheiro, Fiona Sisso, Sébastien Wartelle, Yann Parc, Brigitte Fauroux, Thierry Bégué, Hubert Johanet, Françoise Denoyelle, Erea-Noël Garabédian, and François Simon

Subjects
surgeon, technical skills, non-technical skills, surgery, survey, Medicine (General), R5-920
Abstract

BackgroundThe definition of a great surgeon is usually reported by surgeons themselves. The objective of the study was to define a multifaceted definition of a great surgeon, by confronting patients', healthcare workers', and surgeons' perspectives.Study designAn online open-ended questionnaire was created to identify three qualities and three shortcomings defining a great surgeon. Age, gender, and profession of respondents were collected. Responses with a similar meaning were combined into word groups and labeled within four themes: human qualities, technical surgical skills (TSS), non-technical skills (NTS), and knowledge. Multivariate analyses were conducted between themes and respondent characteristics.ResultsFour thousand seven hundred and sixty qualities and 4,374 shortcomings were obtained from 1,620 respondents including 385 surgeons, 291 patients, 565 operating theater (OT) health professionals, and 379 non-OT health professionals. The main three qualities were dexterity (54% of respondents), meticulousness (18%), and empathy (18%). There was no significant difference between professional categories for TSS. Compared with surgeons, non-OT health professionals and patients put more emphasis on human qualities (29 vs. 39% and 42%, respectively, p < .001). OT health professionals referred more to NTS than surgeons (35 vs. 22%, p < 0.001). Knowledge was more important for surgeons (19%) than for all other professional categories (p < 0.001).ConclusionsThis survey illustrates the multifaceted definition of a great surgeon. Even if dexterity is a major quality, human qualities are of paramount importance. Knowledge seems to be underestimated by non-surgeons, although it essential to understand the disease and preparing the patient and OT team for the procedure.

Published
2023
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3. Molecular profiling of anal Paget’s disease and underlying anal adenocarcinoma highlights their common origin

Author

Yaëlle Bellahsen-Harrar, Marie Boisson, Baptiste Louveau, Barouyr Baroudjian, Thomas Aparicio, Valentine Ferré, Yann Parc, Aurélie Sadoux, Fanélie Jouenne, Maxime Battistella, Céleste Lebbé, and Samia Mourah

Subjects
Extramammary Paget Disease, Anal adenocarcinoma, Molecular profiling, Cell of origin, Immunotherapy, Targeted therapies, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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4. Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands

Author

Morgane Modoux, Nathalie Rolhion, Jeremie H. Lefevre, Cyriane Oeuvray, Petr Nádvorník, Peter Illes, Patrick Emond, Yann Parc, Sridhar Mani, Zdenek Dvorak, and Harry Sokol

Subjects
Microbiota, AhR, butyrate, FICZ, HDAC, CYP1A1, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Aryl hydrocarbon receptor (AhR) is a critical player in the crosstalk between the gut microbiota and its host. However, factors regulating AhR within the gut, which is a complex metabolomic environment, are poorly understood. This study investigates the effect of a combination of metabolites on the activation mechanism of AhR. AhR activity was evaluated using both a luciferase reporter system and mRNA levels of AhR target genes on human cell lines and human colonic explants. AhR activation was studied by radioligand-binding assay, nuclear translocation of AhR by immuofluorescence and protein co-immunoprecipitation of AhR with ARNT. Indirect activation of AhR was evaluated using several tests and inhibitors. The promoter of the target gene CYP1A1 was studied both by chromatin immunoprecipitation and by using an histone deacetylase HDAC inhibitor (iHDAC). Short-chain fatty acids, and butyrate in particular, enhance AhR activity mediated by endogenous tryptophan metabolites without binding to the receptor. This effect was confirmed in human intestinal explants and did not rely on activation of receptors targeted by SCFAs, inhibition of AhR degradation or clearance of its ligands. Butyrate acted directly on AhR target gene promoter to reshape chromatin through iHDAC activity. Our findings revealed that butyrate is not an AhR ligand but acts as iHDAC leading to an increase recruitment of AhR to the target gene promoter in the presence of tryptophan-derived AhR agonists. These data contribute to a novel understanding of the complex regulation of AhR activation by gut microbiota-derived metabolites.

Published
2022
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5. Identification of Positively and Negatively Selected Driver Gene Mutations Associated With Colorectal Cancer With Microsatellite InstabilitySummary

Author

Vincent Jonchere, Laetitia Marisa, Malorie Greene, Alain Virouleau, Olivier Buhard, Romane Bertrand, Magali Svrcek, Pascale Cervera, Anastasia Goloudina, Erell Guillerm, Florence Coulet, Samuel Landman, Toky Ratovomanana, Sylvie Job, Mira Ayadi, Nabila Elarouci, Lucile Armenoult, Fatiha Merabtene, Sylvie Dumont, Yann Parc, Jérémie H. Lefèvre, Thierry André, Jean-François Fléjou, Agathe Guilloux, Ada Collura, Aurélien de Reyniès, and Alex Duval

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Recent studies have shown that cancers arise as a result of the positive selection of driver somatic events in tumor DNA, with negative selection playing only a minor role, if any. However, these investigations were concerned with alterations at nonrepetitive sequences and did not take into account mutations in repetitive sequences that have very high pathophysiological relevance in the tumors showing microsatellite instability (MSI) resulting from mismatch repair deficiency investigated in the present study. Methods: We performed whole-exome sequencing of 47 MSI colorectal cancers (CRCs) and confirmed results in an independent cohort of 53 MSI CRCs. We used a probabilistic model of mutational events within microsatellites, while adapting pre-existing models to analyze nonrepetitive DNA sequences. Negatively selected coding alterations in MSI CRCs were investigated for their functional and clinical impact in CRC cell lines and in a third cohort of 164 MSI CRC patients. Results: Both positive and negative selection of somatic mutations in DNA repeats was observed, leading us to identify the expected true driver genes associated with the MSI-driven tumorigenic process. Several coding negatively selected MSI-related mutational events (n = 5) were shown to have deleterious effects on tumor cells. In the tumors in which deleterious MSI mutations were observed despite the negative selection, they were associated with worse survival in MSI CRC patients (hazard ratio, 3; 95% CI, 1.1–7.9; P = .03), suggesting their anticancer impact should be offset by other as yet unknown oncogenic processes that contribute to a poor prognosis. Conclusions: The present results identify the positive and negative driver somatic mutations acting in MSI-driven tumorigenesis, suggesting that genomic instability in MSI CRC plays a dual role in achieving tumor cell transformation. Exome sequencing data have been deposited in the European genome–phenome archive (accession: EGAS00001002477). Keywords: Colorectal Cancer, Microsatellite Instability, Tumorigenic Process, Driver Gene Mutations, Positive and Negative Selection

Published
2018
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6. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

Author

Laetitia Marisa, Aurélien de Reyniès, Alex Duval, Janick Selves, Marie Pierre Gaub, Laure Vescovo, Marie-Christine Etienne-Grimaldi, Renaud Schiappa, Dominique Guenot, Mira Ayadi, Sylvain Kirzin, Maurice Chazal, Jean-François Fléjou, Daniel Benchimol, Anne Berger, Arnaud Lagarde, Erwan Pencreach, Françoise Piard, Dominique Elias, Yann Parc, Sylviane Olschwang, Gérard Milano, Pierre Laurent-Puig, and Valérie Boige

Subjects
Medicine
Abstract

BackgroundColon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.Methods and findingsFresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.ConclusionsWe describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.

Published
2013
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7. StomaCare: quality of life impact after enhanced follow‐up of ostomy patients by a home healthcare nursing service—a multicentre, randomized, controlled trial

Author

Charles de Ponthaud, Morgan Roupret, Dewi Vernerey, François Audenet, Antoine Brouquet, Eddy Cotte, Xavier Cuvillier, Frédéric Kanso, Guillaume Meurette, Patrick Ledaguenel, Léon Maggiori, Yann Neuzillet, Mehdi Ouaissi, Mathieu Roumiguié, Véronique Phé, Nam‐Son VUONG, Yann Parc, and Jérémie H. Lefèvre

Subjects
Gastroenterology
Abstract

A stoma exposes patients to several complications which could impair their quality of life (QoL). In the last decade, the market for stoma therapy in France has evolved, with a significant increase in the activities of home health providers, meeting a need for patient follow-up and companionship. International studies have demonstrated the impact of the stoma therapist (ST) follow-up on the improvement of an ostomy patient's QoL. However, the impact of home stoma nurse management has not been analysed. In this context we would like to assess the added value on health-related QoL from the enhanced follow-up of ostomy patients by STs.This is a randomized, controlled, open, national and multicentre trial (12 centres) which includes patients with an ostomy who benefit from either standard follow-up or from an enhanced and personalized follow-up with, in particular, regular consultations with an ST after discharge. The primary end-point is the 3-month QoL score obtained from the Stoma-QoL questionnaire. The secondary end-points are satisfaction of the care, comparison of QoL scores (Stoma-QoL and EuroQuol EQ-5D) and the economic gains by calculating the consumption of resources between the two arms. There will be a modified intention-to-treat analysis with 6-month follow-up in both study arms.The StomaCare trial will be the first randomized controlled study in France to evaluate the impact on QoL of an enhanced follow-up at home of ostomy patients by an ST.

Published
2022

8. Postoperative outcomes after laparoscopic or open gastrectomy. A national cohort study of 10,343 patients

Author

Ben Creavin, Alexandre Challine, Sandrine Katsahian, Andrea Lazzati, Bertrand Dousset, Thibault Voron, Jérémie H. Lefevre, Yann Parc, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Chirurgie digestive, hépato-biliaire et endocrinienne [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), St Vincent's University Hospital, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Gestionnaire, HAL Sorbonne Université 5

Subjects
Male, Reoperation, medicine.medical_specialty, Hospitals, Low-Volume, medicine.medical_treatment, Population, National cohort, Cohort Studies, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Oesophageal stricture, Gastrectomy, Stomach Neoplasms, Open approach, medicine, Humans, Mortality, education, Laparoscopy, Aged, Aged, 80 and over, Laparotomy, education.field_of_study, medicine.diagnostic_test, business.industry, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, General Medicine, Length of Stay, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Esophageal Stenosis, Female, 030211 gastroenterology & hepatology, Morbidity, Gastric cancer, business, Hospitals, High-Volume
Abstract

International audience; BackgroundLaparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical techniques comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy.MethodsA retrospective study (2013–2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG).ResultsA total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open = 39.4% vs. Laparoscopy = 32.6%, p = 0.01), length of stay (Open = 14[10–21] vs. Laparoscopy = 11[8–17] days, p

Published
2021

9. Advanced colonic cancer with clinically suspected bladder invasion: Outcomes and prognosis from a multicentric study of 117 patients from the FRENCH research group

Author

Cindy Vuillermet, Hélène Meillat, Gilles Manceau, Ben Creavin, Clarisse Eveno, Stéphane Benoist, Yann Parc, Jérémie H. Lefevre, Sara Arfa, Paul-Noël Dumont, Hortense Boullenois, David Fuks, Mehdi Ouaissi, Leonor Benhaim, Marie Selvy, Jean-Jacques Tuech, Zaher Lakkis, Renato Lupinacci, Antoine Epin, Sophie Deguelte, Guillaume Passot, Bertrand Trilling, Cécile Jarlot-Gas, Muriel Mathonnet, David Moszkowicz, Leila M’Harzi, Laura Beyer Berjot, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Chirurgie Digestive et Endocrinienne [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université - Faculté de médecine Pitié Salpétrière, CHU Pitié-Salpêtrière [AP-HP], St Vincent's University Hospital, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

Subjects
Male, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Urinary Bladder, Urology, 030230 surgery, Cystectomy, urologic and male genital diseases, Resection, 03 medical and health sciences, advanced colon cancer, 0302 clinical medicine, Colon surgery, medicine, Adjuvant therapy, Humans, Neoplasm Invasiveness, Neoadjuvant therapy, Aged, Retrospective Studies, Aged, 80 and over, bladder invasion, business.industry, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, 3. Good health, Colonic cancer, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Surgery, local recurrence, Neoplasm Recurrence, Local, business, urinary tract involvement, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, enbloc resection
Abstract

International audience; BackgroundBladder invasion by colon cancer is rare; however, its management is still controversial. Our objective was to report outcomes and identify risk factors for local recurrence in colon cancer with clinically suspected bladder invasion.MethodsWe conducted a retrospective study in 23 centers in France. All patients who underwent colon surgery with bladder resection (2010–2017) were included. Metastatic and recurrent colon cancers were excluded.ResultsOne hundred and seventeen patients (men = 73) were included. Partial cystectomy occurred in 108 patients (92.3%), with a total cystectomy occurring in 9 patients (7.7%). Neoadjuvant treatment was given to 31 patients (26.5%). Major morbidity was 20.5%. R0 resection rates were 87.2%. Histologically confirmed bladder invasion was present in 47%. Thirty-four patients were pN+, while 60 patients (51.3%) received adjuvant chemotherapy. Mean follow-up was 33.8 months. Three-year overall survival and disease-free survival were 82.9% and 59.5%. Rates of local recurrence and distant recurrence were 14.5% and 18.8%, respectively; the local recurrences (11/17; 65%) were in the bladder, while 4 of these patients had a bladder recurrence despite not having histologically confirmed bladder invasion at the index surgery. The rate of bladder recurrence after histologic bladder invasion was 13% (7/55), while the rate of bladder recurrence without primary bladder invasion was 7% (4/62) (P = .343). Neoadjuvant therapy, type of cystectomy, and adjuvant therapy did not influence local recurrence (P > .445 each). R1 bladder resections, when compared with a R0 bladder resections, were associated with an increased rate of local recurrence (63% vs 10%; P < .0001).ConclusionClinically suspected bladder invasion increases local recurrence even in the absence of histologically confirmed bladder invasion. Only complete resections with R0 margins decrease local recurrence. Careful, detailed postoperative surveillance is required, even without pathologic bladder invasion.

Published
2020

10. Pathological Tumor Response Following Immune Checkpoint Blockade for Deficient Mismatch Repair Advanced Colorectal Cancer

Author

Kaysia Ludford, Raphael Colle, Thierry André, Magali Svrcek, George J. Chang, Jane V Thomas, Michael J. Overman, Yann Parc, Romain Cohen, Van K. Morris, Wai Chin Foo, and Scott Kopetz

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Cell cycle checkpoint, Colorectal cancer, Brief Communication, DNA Mismatch Repair, Preoperative care, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Neoplasm Metastasis, Prospective cohort study, Immune Checkpoint Inhibitors, Pathological, Aged, 030304 developmental biology, 0303 health sciences, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Immune checkpoint, Blockade, 030220 oncology & carcinogenesis, Microsatellite Instability, Colorectal Neoplasms, business
Abstract

Immune checkpoint inhibition (CPI) for metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) demonstrates high clinical activity that appears durable, but the impact of CPI on pathological tumor response is unknown. In this retrospective analysis, our objective was to assess pathological response and clinical outcomes in dMMR mCRC patients treated with CPI prior to surgical resection of primary and/or metastatic tumor. Among 121 advanced dMMR mCRC patients treated with CPI at 2 institutions between November 2016 and December 2018, 14 underwent surgery. Pathologic complete response was noted in the resected specimens of 13 patients despite the presence of residual tumor on preoperative imaging in 12 of those patients. With median follow-up of 9 months, no patients have had disease relapse or progression. For this small retrospective study, the data suggest that residual radiographic tumor may not require systematic resection following response to anti-PD1–based therapy. However, larger prospective studies are warranted.

Published
2020

11. Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis

Author

Jérémie H. Lefevre, Sandrine Katsahian, Yann Parc, Bertrand Dousset, Nicola de’Angelis, Andrea Lazzati, Alexandre Challine, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Intercommunal de Créteil (CHIC), École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)

Subjects
Male, 030230 surgery, Cohort Studies, 0302 clinical medicine, Postoperative Complications, MESH: Aged, 80 and over, MESH: Postoperative Complications, Medicine, MESH: COVID-19, Hospital Mortality, MESH: Elective Surgical Procedures, MESH: Cohort Studies, Digestive System Surgical Procedures, MESH: Digestive System Surgical Procedures, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH: Middle Aged, Middle Aged, MESH: Case-Control Studies, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Cohort, Quarantine, Female, France, medicine.symptom, MESH: Quarantine, Cohort study, medicine.medical_specialty, Population, MEDLINE, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Asymptomatic, Article, 03 medical and health sciences, Internal medicine, Humans, MESH: Hospital Mortality, Risk factor, education, Aged, MESH: Humans, business.industry, Outbreak, COVID-19, MESH: Male, MESH: France, Case-Control Studies, Propensity score matching, Surgery, business, MESH: Female
Abstract

International audience; Background: The outbreak of coronavirus disease 2019 (COVID-19) infection has led to the reorganization of hospital care in several countries. The objective was to report the postoperative mortality after elective digestive resections in a nationwide cohort during the lockdown period.Methods: This analytic study was performed using a national billing database (the Programme de Médicalisation des Systèmes d’Informations). Patients who underwent elective digestive resections were divided in 2 groups: the lockdown group defined by hospital admissions between March 17 and May 11, 2020; and the control group, defined by hospital admissions during the corresponding period in 2019. Groups were matched on propensity score, geographical region, and surgical procedure. The primary outcome was the postoperative mortality.Results: The overall population included 15,217 patients: 9,325 patients in the control group and 5,892 in the lockdown group. The overall surgical activity was decreased by 37% during the lockdown period. The overall in-hospital mortality during the hospital stay was 2.7%. After matching and adjustment, no dif-ference in mortality between groups was reported (OR ¼ 1.05; 95% CI: 0.83e1.34; P ¼ .669). An asymptomatic COVID-19 infection was a risk factor for a 2-fold increased mortality, whereas a symp-tomatic COVID-19 infection was associated with a 10-fold increased mortality.Conclusion: Despite a considerable reduction in the surgical activity for elective digestive resections during the lockdown period, mortality remained stable on a nationwide scale in COVID-free patients. These findings support that systematic COVID-19 screening should be advocated before elective gastrointestinal surgery and that all efforts should be made to maintain elective surgical resection for cancer during the second wave in COVID-free patients.

Published
2021

12. Colorectal screening: We have not caught up. A surge of colorectal cancer after the coronavirus disease 2019 (COVID-19) pandemic?

Author

Alexandre Challine, Andrea Lazzati, Sandrine Katsahian, Yann Parc, Jeremie H. Lefevre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
SARS-CoV-2, COVID-19, Humans, Surgery, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Colorectal Neoplasms, Pandemics, Early Detection of Cancer
Abstract

International audience

Published
2021

13. Functional outcomes of patients undergoing successful redo surgery after failed primary colorectal or coloanal anastomosis for rectal cancer

Author

Hortense Boullenois, Jérémie H. Lefevre, Mélanie Calmels, Najim Chafai, Yann Parc, M. Collard, Ben Creavin, Clotilde Debove, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Anastomotic Leak, 030230 surgery, Anastomosis, Stoma, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Quality of life, Medicine, Humans, Treatment Failure, Coloanal anastomosis, Aged, Aged, 80 and over, Rehabilitation, business.industry, Anastomosis, Surgical, Surgical Stomas, Colorectal anastomosis, Middle Aged, medicine.disease, Prognosis, 3. Good health, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Redo surgery, Retreatment, Quality of Life, Female, business, Colorectal Neoplasms, Factor Analysis, Statistical
Abstract

International audience; Background: After a failure of a colorectal or coloanal anastomosis, redo anastomotic surgery aims to avoid the risk of permanent stoma but, overall, to provide a satisfactory functional result and quality of life. Very limited data exist regarding the long-term results after a successful redo anastomosis. The present study aimed to report the long-term functional outcomes and quality of life in patients after a successful redo colorectal anastomosis or coloanal anastomosis.Methods: Between 2007 and 2018, all patients who had a successful restoration of bowel continuity after a failed primary anastomosis performed for a rectal cancer were included. Functional outcomes and quality of life were assessed using the low anterior rectal syndrome score and the Gastrointestinal Quality of Life Index.Results: One hundred and twenty-seven patients were eligible for inclusion in this study, with long-term functional outcomes assessed in 73 patients (57%). After a median follow-up of 69 months, 31 patients presented no or minor low anterior rectal syndrome (42%), whereas 31 patients reported a major low anterior rectal syndrome (42%). A definitive stoma was confectioned in 11 patients (15%), despite the technical success of redo anastomosis due to poor functional results. Only operative interval

Published
2021

14. Duodenal adenomas and cancer in MUTYH-associated polyposis: an international cohort study

Author

Andrew Latchford, A. Alonso Sanchez, Patrick M. Lynch, Matthew Mort, Joanna J Hurley, Maria Teresa Ricci, E. Meuser, Marco Vitellaro, Hannah West, A. Backman, Yann Parc, Susan K. Clark, M. R. Aznárez, Frederik J. Hes, Sunil Dolwani, O. Vinet, H. Leon Brito, Maureen E. Mork, Chrystelle Colas, M. Navarro Garcia, S. Gonzalez Romero, Sarah-Jane Walton, Hala Jundi, Gabriel Capellá, S. Kelland, Zeinab Ghorbanoghli, K van der Tuin, Hans F. A. Vasen, Julian R. Sampson, Jan Björk, Evelien Dekker, Jean-Christophe Saurin, Eduardo Vilar, Laura E. Thomas, M. Gonn, Maartje Nielsen, Clinical sciences, Medical Genetics, Gastroenterology and Hepatology, APH - Quality of Care, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Adult, Male, medicine.medical_specialty, Duodenum, Gastroenterology, DNA Glycosylases, Familial adenomatous polyposis, Adenomatous Polyps, Young Adult, Duodenal Neoplasms, Internal medicine, Prevalence, medicine, Humans, Genetics(clinical), Prospective Studies, Intestinal Mucosa, Endoscòpia, Polyposis, Càncer, Duodenoscopy, Aged, Cancer, Aged, 80 and over, Hepatology, Spigelman Stage, business.industry, MUTYH-Associated Polyposis, Endoscopy, Middle Aged, medicine.disease, digestive system diseases, Estudi de casos, Female, Case studies, business, Cohort study
Abstract

Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions.

Published
2021

15. Postoperative diagnostic revision for Crohn disease after subtotal colectomy for inflammatory bowel disease

Author

Magali Svrcek, Hélène Hermand, Jérémie H. Lefevre, Najim Chafai, Clotilde Debove, Yann Parc, Conor Shields, and Laurent Beaugerie

Subjects
medicine.medical_specialty, medicine.medical_treatment, Disease, Inflammatory bowel disease, Gastroenterology, Stoma, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, medicine, Humans, Colitis, Colectomy, Retrospective Studies, business.industry, Retrospective cohort study, Hepatology, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, 3. Good health, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Colitis, Ulcerative, business
Abstract

Subtotal colectomy (STC) is performed for severe acute and refractory colitis. The diagnosis can be difficult even after the surgery when colectomy specimen has overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD). The aim of this study was to evaluate the rate of postoperative diagnostic revision to CD after surgery and determine predictor factors. Retrospective study of 110 patients who underwent STC (2005–2018). Preoperative diagnosis comprised UC = 80 (73%), CD = 11 (10%), and unclassified colitis (IBDU = 19, 17%). Initial diagnosis of IBDU and UC was modified to CD in 6 patients (6%) after STC. The final diagnosis after the follow-up of 10 ± 6 years switched from CD for 8 patients (9%). The multivariate analysis showed that patients with a colitis evolving for less than 10 years and initial diagnosis of IBDU were the two independent factors associated with an increased risk of diagnosis change to CD (p = 0.03; p = 0.016). At the end of the follow-up, 15 patients (14%) had a definitive stoma. In patients with IBD, attention must be paid to determine the right restorative strategy to patients with an evolution of the disease less than 10 years or with IBDU who are more at risk to have a diagnosis change to CD after STC.

Published
2020

16. Social deprivation aggravates post-operative morbidity in carcinologic colorectal surgery: Results of the COINCIDE multicenter study

Author

C. Penna, Yann Parc, M. Hirsch, Marc Pocard, Groupe Coincide, Alexis Laurent, A. Civet, Arnaud Alves, and S. Msika

Subjects
education.field_of_study, medicine.medical_specialty, Colorectal cancer, business.industry, Population, General Medicine, medicine.disease, Colorectal surgery, Social deprivation, Postoperative Complications, Internal medicine, Relative risk, medicine, Humans, Social determinants of health, Prospective Studies, Risk factor, Morbidity, education, Prospective cohort study, business, Colorectal Neoplasms, Colorectal Surgery, Digestive System Surgical Procedures, Aged
Abstract

Summary Aim of the study Evaluate the impact of social deprivation on morbidity and mortality in surgery for colorectal cancer. Methods The COINCIDE prospective cohort included nearly 2,000 consecutive patients operated on for colorectal cancer at the Assistance Publique-Hospitals of Paris (AP-HP) from 2008 to 2010. The data on these patients were crossed with the PMSI administrative database. The European Social Deprivation Index (EDI) was calculated for each patient and classified into five quintiles (quintiles 4 and 5 being the most disadvantaged patients). Thirty-day post-operative morbidity was determined according to the Dindo-Clavien classification, with a Had®Hoc re-analysis of each file. Statistical analysis was performed using the proprietary Q-finder® algorithm. Results One thousand two hundred and fifty nine curative colorectal resections were analyzed. Mortality was 2.7% and severe morbidity (Dindo-Clavien ≥ 3) occurred in 16.4%. Mortality was not statistically significantly increased among the most disadvantaged who made up almost two thirds of the population (64.2%). Patients in quintiles 4 and 5 had a statistically significant increase in severe morbidity. The relative risk remained 1.5 even after adjustment for the known risk factors found in the analysis: age > 70 years, ASA score, urgency, and laparotomy. Conclusions The EDI represents an independent risk factor for severe morbidity after carcinologic colorectal resection. This study suggests that the determinants of health are multidimensional and do not depend solely on the quality and performance of the care system. The inclusion of this index in our surgical databases is therefore necessary, as is its use in health policy for the distribution of resources.

Published
2020

17. Patients’ refusal as major limitation of early discharge after colorectal resection in an enhanced recovery program

Author

Anais Laforest, Thomas Lescot, Jérémie H. Lefevre, Conor Shields, M. Collard, Yann Parc, Christophe Gutton, Morgan Anyla, Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, Young Adult, 0302 clinical medicine, Colorectal surgery, medicine, Humans, Early discharge, Colectomy, Enhanced recovery, Aged, Aged, 80 and over, Proctectomy, business.industry, Vascular surgery, Length of Stay, Middle Aged, Patient Discharge, 3. Good health, Surgery, Cardiac surgery, Cardiothoracic surgery, 030220 oncology & carcinogenesis, Defecation, Feasibility Studies, 030211 gastroenterology & hepatology, Female, Discharge, Morbidity, business, Colorectal Neoplasms, Enhanced Recovery After Surgery, Readmission, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Abdominal surgery
Abstract

International audience; Purpose : The reduction of length of hospitalization without compromising the patient's safety constitutes the challenge of the enhanced recovery after surgery (ERAS) programs. Our aim was to evaluate the feasibility and safety of a 3-day hospitalization after colectomy and 5-day hospitalization after proctectomy in the setting of an ERAS program. Methods : An ERAS program was prospectively proposed to all patients who required a colorectal resection (January 2014-December 2018) with a 3- or 5-day discharge objective. The success of the program was defined by a 3-/5-day hospitalization without complications and without readmissions.Results : Among 283 patients included, 232 patients had a colectomy (82%) and 51 (18%) patients a proctectomy. Eighty-six patients experienced complications (30%) including fifteen severe complications (5%). Mean hospital stay was 5.1 ± 3.7 (2-33) days. A total of 136 patients (48%) were discharged at 3-/5-day, within 9 were readmitted (3%). Discharge was delayed after 3-/5-day for complications (n = 65, 23%), CRP > 120 (n = 45, 16%) or refusal without medical reason (n = 37, 13%). The success rate of the program was 45% (n = 127). This success rate was similar between colectomy and proctectomy (p = 0.277) and between right and left colectomy (p = 0.450). In multivariate analysis, predictive factors associated with the program success were intraoperative use of lidocaine (OR 2.1 [1.1-4.1], p = 0.022), time to remove perfusion ≤ 2 days (OR 10.3 [5.4-19.6], p = 0.001), time to recover bowel movement ≤ 2 days (OR 4.0 [1.7-9.6], p = 0.002) and time to walk out of the room ≤ 2 days (OR 2.6 [1.1-6.0], p = 0.022).Conclusion : Integrating a realistic hospitalization duration objective into an ERAS program guarantees its safety, feasibility and effectiveness in reducing hospitalization duration.

Published
2020

18. The management of perineal hernia following abdomino-perineal excision for cancer

Author

M Luong, Najim Chafai, Thibault Voron, Ben Creavin, K Bertrand, Emmanuel Tiret, Yann Parc, Jérémie H. Lefevre, Clotilde Debove, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
Male, MESH: Carcinoma, Hernia, Colorectal cancer, [SDV]Life Sciences [q-bio], 030230 surgery, MESH: Surgical Mesh, Perineum, Surgical Flaps, 0302 clinical medicine, MESH: Aged, 80 and over, Recurrence, Abdomen, Rectal cancer, Perineal hernia, Aged, 80 and over, MESH: Aged, Proctectomy, MESH: Middle Aged, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Female, MESH: Neoplasm Recurrence, Local, Abdomino-perineal resection, Adult, medicine.medical_specialty, MESH: Abdomen, Resection, 03 medical and health sciences, medicine, MESH: Herniorrhaphy, Humans, MESH: Perineum, Herniorrhaphy, Aged, Retrospective Studies, MESH: Humans, Rectal Neoplasms, business.industry, MESH: Proctectomy, Carcinoma, Cancer, MESH: Rectal Neoplasms, MESH: Adult, MESH: Retrospective Studies, Surgical Mesh, MESH: Surgical Flaps, medicine.disease, MESH: Hernia, Combined approach, MESH: Male, Surgery, MESH: Recurrence, Neoplasm Recurrence, Local, business, Complication, MESH: Female, Abdominal surgery
Abstract

International audience; Purpose: Perineal hernia (PH) is a tardive complication following abdomino-perineal resection (APR). Many repair methods are described and evidences are lacking. The aim of this study was to report PH management, analyze surgery outcomes and review the available literature.Methods: We retrospectively included all consecutive PH repair after APR performed between 2001 and 2017. We recorded data on APR surgery, PH symptoms and repair, and follow-up (recurrence and morbidity). Literature review included published articles on PubMed between 1960 and 2017.Results: 24 PH repairs were included. The approach was perineal N = 16, abdominal N = 5 and combined N = 3. A biological mesh was used for 17, a synthetic for 5 and a flap for 2 patients. The median follow-up was 25 months. Overall morbidity was 37.5% (N = 9): 37.5% for the perineal, 20% for the abdominal, and 66.7% for the combined approach. Complications occurred in 35.3% of biological and 20% of synthetic mesh repairs. Recurrence rate was 41.7%, similar for biological (n = 8, 47.1%) and synthetic meshs (n = 2; 40%). No recurrence occurred in the flap group. Depending of the approach, we found 50% for perineal (n = 8) and 40% of the abdominal cohort (N = 2). Among twelve studies, recurrence rates ranged from 0 to 66.7%. Abdominal or laparoscopic approach with synthetic mesh was associated with less recurrences (0 and 12.5% respectively) and complications (37.5% and 9.5%).Conclusions: Recurrences following PH repair are high irrespective of the repair technique. More studies are necessary to identify PH risk factors and decide the appropriate perineal reconstruction.

Published
2020

19. High IGF1R protein expression correlates with disease-free survival of patients with stage III colon cancer

Author

Christèle Desbois-Mouthon, Aziz Zaanan, Claire Calmel, Christophe Louvet, Françoise Praz, Hélène Blons, Julien Taieb, Brice Gayet, Pierre Validire, Yann Parc, Yves Le Bouc, Julie Henriques, Claire Goumard, Magali Svrcek, Fatiha Merabtene, Jean-François Fléjou, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de chirurgie digestive, générale et cancérologique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Institut Mutualiste de Montsouris (IMM), Service de gastroenterologie [CHU HEGP], and Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Cancer Research, Multivariate analysis, Colorectal cancer, Kaplan-Meier Estimate, Gastroenterology, Receptor, IGF Type 1, 0302 clinical medicine, IGF1R, Stage (cooking), Receptor, Aged, 80 and over, Reverse Transcriptase Polymerase Chain Reaction, General Medicine, Middle Aged, Immunohistochemistry, 3. Good health, Colon cancer, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Colonic Neoplasms, Molecular Medicine, Female, Adult, medicine.medical_specialty, IGF-II/IGF2, Disease-free survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, RNA, Messenger, MSI, Insulin-like growth factor 1 receptor, Aged, Neoplasm Staging, Retrospective Studies, Proportional hazards model, business.industry, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, KRAS/BRAF, body regions, 030104 developmental biology, business
Abstract

International audience; Purpose: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC).Methods: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Associations of markers with DFS were analysed using Cox proportional hazards models.Results: Hundred and fifty-one CC patients were included (median age, 66.6 years; female, 54.3%). Low levels of IGF1R and IGF-II protein expression were observed in 16.1% and 10.7% of the cases, respectively. No significant differences in clinicopathological characteristics between patients with tumours expressing low IGF1R or IGF-II protein levels and those with high levels were observed. A low IGF1R protein expression was found to be significantly associated with a shorter DFS (HR 3.32; 95% CI, 1.7-6.31; p = 0.0003), while no association was observed between IGF-II protein expression and DFS (HR 0.91; 95% CI, 0.28-2.96; p = 0.87). In a multivariate analysis, IGF1R protein status remained an independent prognostic factor for DFS (HR 2.73; 95% CI, 1.40-5.31; p = 0.003). Furthermore, we found that neither IGF1R nor IGF2 mRNA expression levels as measured by qRT-PCR correlated with the respective protein expression levels as assessed by immunohistochemistry. Neither of the mRNA expression levels was significantly associated with DFS.Conclusions: From our data we conclude that low IGF1R protein expression represents a poor prognostic biomarker in stage III colon cancer.

Published
2020

20. Prognostic value of tumor deposits in rectal cancer: A monocentric series of 505 patients

Author

Alexandre Challine, Magali Svrcek, Morgane Bouquot, Jérémie H. Lefevre, Yann Parc, Olivier Benoit, Najim Chafai, Ben Creavin, Clotilde Debove, Thibault Voron, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), and Service de Pathologie [CHU Saint-Antoine]

Subjects
Male, medicine.medical_specialty, Colorectal cancer, nodal staging, Perineural invasion, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, tumor deposits, 0302 clinical medicine, N1c, Internal medicine, Rectal Adenocarcinoma, Medicine, Humans, Stage (cooking), rectal cancer, Lymph node, Aged, Neoplasm Staging, business.industry, Rectal Neoplasms, PN category, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Chemoradiotherapy, Middle Aged, medicine.disease, Prognosis, 3. Good health, medicine.anatomical_structure, Colonic cancer, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Synchronous metastasis, 030211 gastroenterology & hepatology, Surgery, Female, business
Abstract

International audience; Background and objectives: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer.Methods: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis.Results: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001).Conclusion: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

Published
2020

21. Is ileostomy mandatory for ileal pouch-anal anastomosis? A propensity matched analysis of 388 procedures

Author

Thevy Hor, Najim Chafai, M. Collard, Clotilde Debove, Jérémie H. Lefevre, Ben Creavin, Omar Ahmed, Yann Parc, Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, Anastomotic Leak, ileostomy, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Anastomosis, Familial adenomatous polyposis, Young Adult, 03 medical and health sciences, Ileostomy, 0302 clinical medicine, medicine, Humans, Child, Propensity Score, education, Aged, Aged, 80 and over, 2. Zero hunger, education.field_of_study, business.industry, Proctocolectomy, Standard treatment, Proctocolectomy, Restorative, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Surgery, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Propensity score matching, Ileal pouch-anal anastomosis, Colitis, Ulcerative, Female, business
Abstract

International audience; Background: Restorative proctocolectomy with ileal-pouch-anal anastomosis is the standard treatment for patients with ulcerative colitis or familial adenomatous polyposis. This procedure has undergone many changes and varies in 1, 2, or 3 stages. A diverting ileostomy can be created with the aim of reducing the consequence of an anastomotic leakage; however, its use is still unknown.Method: The value of defunctioning ileostomy was studied in a population of 388 patients undergoing restorative proctocolectomy with ileal-pouch-anal anastomosis between 2005 and 2017. Leakage rate and postoperative morbidity were assessed. Patients were matched on a propensity score using the following criteria: American Society of Anesthesiologists score, body mass index, diagnosis, surgical approach, and year.Results: Two hundred and three ileal-pouch-anal anastomosis for ulcerative colitis and 185 for familial adenomatous polyposis were performed representing 165 1-stage (61.6%), 79 classic 2-stage, 74 modified 2-stage, and 70 3-stage procedures. Regardless of the surgical strategy adopted, there were no significant differences in postoperative morbidity (P = .416), leakage rate (P = .369), and reoperation (P = .237), whether a diverting ileostomy was performed or not. After propensity score matching, there was no significant difference in postoperative morbidity (P = .363), leakage rate (P = .247), or reoperation (P = .243). The rate of persistent ileostomy at 1 year was higher in cases of classic 2-stage or 3-stage procedures (P = .036).Conclusion: After propensity score matching, defunctioning ileostomy for ileal-pouch-anal anastomosis does not reduce leakage rate or postoperative morbidity, independent of the surgical strategy. Systematic ileostomy for ileal-pouch-anal anastomosis is probably not justified, and its place should be redefined in a randomized trial.

Published
2020

22. Can a Local Drainage Salvage a Failed Colorectal or Coloanal Anastomosis? A Prospective Cohort of 54 Patients

Author

Olivier Benoit, Yann Parc, Clotilde Debove, Alexandre Challine, Jérémie H. Lefevre, Ben Creavin, Najim Chafai, Thibault Voron, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Male, medicine.medical_specialty, coloanal anastomosis, Colon, Anastomotic Leak, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Anastomosis, anastomotic leakage, 03 medical and health sciences, 0302 clinical medicine, Colon surgery, Medicine, Humans, Prospective Studies, Drainage, Prospective cohort study, Coloanal anastomosis, Colectomy, Salvage Therapy, business.industry, Rectal Neoplasms, Anastomosis, Surgical, Gastroenterology, Follow up studies, Rectum, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Middle Aged, 3. Good health, Surgery, anastomotic drainage, 030220 oncology & carcinogenesis, outcome, Observational study, Female, business, Follow-Up Studies
Abstract

Local drainages can be used to manage leakage in select patients without peritonitis.The aim of this study was to evaluate the efficacy of drainage procedures in maintaining a primary low anastomosis after anastomotic leakage.A retrospective observational study was performed on a prospectively maintained database.The study was performed between 2014 and 2017 in a tertiary referral center.Patients undergoing rectal resections with either a colorectal or coloanal anastomosis with diverting stoma were identified. Anastomotic leakages requiring a radiological or transanal drainage without peritonitis were included.The primary outcome was the maintenance of the primary anastomosis after local drainage of an anastomotic leakage and stoma reversal.A low anastomosis for rectal cancer with diverting stoma was performed in 326 patients. A total of 77 anastomotic leakages (24%) occurred, of which, 6 (8%) required abdominal surgery, 17 (22%) were treated conservatively (medical management), and 54 (70%) were managed by drainage. Surgical transanal drainage was performed in 21 patients (39%), with radiologic drainage procedures performed in 33 patients (61%). The median interval between surgery and drainage was 13 days (range, 9-21 d). Five patients (9%) required emergency abdominal surgery. Twenty-seven patients (50%) did not require any additional intervention after drainage procedure, whereas 21 patients (39%) underwent redo anastomotic surgery. Forty-three patients (80%) had no stoma at the end of follow-up. Failure to maintain the primary anastomosis after local drainage was associated with increased age (p = 0.04), a pelvic per-operative drainage (p = 0.05), a drainage duration10 days (p = 0.002), the time between surgery and drainage15 days (p = 0.03), a side-to-end or J-pouch anastomosis (p = 0.04), and surgical transanal drainage (p = 0.03).The small sample size of the study was the main limitation.Local drainage procedures maintained primary anastomosis in 50% of cases after an anastomotic leakage. See Video Abstract at http://links.lww.com/DCR/B57. ¿PUEDE UN DRENAJE LOCAL SALVAR UNA ANASTOMOSIS COLORRECTAL O COLOANAL FALLIDA? UNA COHORTE PROSPECTIVO DE 54 PACIENTES: Los drenajes locales se pueden utilizar para controlar las fugas en pacientes seleccionados sin peritonitis.El objetivo de este estudio fue evaluar la eficacia de los procedimientos de drenaje, para mantener una anastomosis primaria baja, después de una fuga anastomótica.Se realizó un estudio observacional retrospectivo en una base de datos mantenida prospectivamente.El estudio se realizó entre 2014-2017, en un centro de referencia terciaria.Se identificaron pacientes sometidos a resecciones rectales con anastomosis colorrectal o coloanal y estoma de derivación. Se incluyeron fugas anastomóticas sin peritonitis, que requirieron drenaje radiológico o transanal.El resultado primario fue el mantenimiento de la anastomosis primaria, después del drenaje local de una fuga anastomótica y la reversión del estoma.Se realizó una anastomosis baja para cáncer rectal con estoma derivativo en 326 pacientes. Se produjeron 77 (24%) fugas anastomóticas, de las cuales 6 (8%) requirieron cirugía abdominal, 17 (22%) fueron tratadas de forma conservadora (tratamiento médico) y 54 (70%) fueron manejadas por drenaje. Se realizó drenaje transanal en 21 pacientes (39%) y procedimientos de drenaje radiológico en 33 pacientes (61%). La mediana del intervalo entre la cirugía y el drenaje fue de 13 días [9-21]. 5 (9%) pacientes requirieron cirugía abdominal de emergencia. Veintisiete (50%) pacientes no requirieron ninguna intervención adicional después del procedimiento de drenaje, mientras que 21 pacientes (39%) se sometieron a una reparación quirúrgica anastomótica. 43 pacientes (80%) no tuvieron estoma al final del seguimiento. El fracaso para mantener la anastomosis primaria después del drenaje local, se asoció con un aumento de la edad (p = 0.04), un drenaje pélvico preoperatorio (p = 0.05), una duración del drenaje10 días (p = 0.002), el tiempo entre la cirugía y el drenaje15 días (p = 0.03), anastomosis termino lateral o bolsa en J (p = 0.04) y drenaje quirúrgico transanal (p = 0.03).El pequeño tamaño de la muestra del estudio fue la principal limitación.Después de la fuga anastomótica, los procedimientos del drenaje local conservaron la anastomosis primaria en el 50% de los casos. Vea el Resumen del Video en http://links.lww.com/DCR/B57.

Published
2020

23. Long‐term functional results and quality of life after redo rectal surgery: delayed versus immediate colo‐anal anastomosis

Author

Thibaut Voron, Ben Creavin, Clotilde Debove, Hortense Boullenois, Jérémie H. Lefevre, Yann Parc, Najim Chafai, Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Vaginal fistula, Colon, medicine.medical_treatment, Anal Canal, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Anastomosis, colo-anal anastomosis, Group B, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Quality of life, Interquartile range, Urinary Fistula, medicine, Humans, 10. No inequality, redo rectal surgery, Retrospective Studies, business.industry, Rectal Neoplasms, Anastomosis, Surgical, Gastroenterology, Rectum, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Syndrome, medicine.disease, 3. Good health, Surgery, GIQLI score, Radiation therapy, Treatment Outcome, Quality of Life, Delayed colo-anal anastomosis, 030211 gastroenterology & hepatology, Female, business, LARS score
Abstract

International audience; AIM: To compare the functional results and quality of life after delayed colo-anal anastomosis (DCAA) or immediate colo-anal anastomosis (ICAA) following redo rectal surgery.METHOD:Twenty-six patients with DCAA between 2014 and 2018 were studied retrospectively (group A). Two control groups were used: 26 ICAA after redo surgery (group B) and 52 colo-anal anastomosis (CAA) after anterior resection (group C). Control groups were matched for age, sex, pelvic radiotherapy and time to surgery. Low Anterior Resection Syndrome (LARS) and Gastrointestinal Quality of Life Index (GIQLI) scores were used to assess function and quality of life.RESULTS: The indications for surgery were comparable for groups A and B: anastomotic failure with chronic sepsis (38% vs 50%, P = 0.40), vaginal fistula (42% vs 42%, P = 1) and urinary fistula (20% vs 8%, P = 0.22) as well as the number of previous abdominal operations (1.3 ± 0.9 vs 1.1 ± 0.6, P = 0.19). The median LARS score in the first 2 years was 30 [interquartile range (IQR) 14-41] for group A, 23 (IQR 0-41) for group B and 22 (IQR 11-37) for group C. After 2 years, the median LARS score improved in each group [A, 21 (IQR 11-35); B, 18 (IQR 5-26); C, 13 (IQR 9-20)], but was still high in group A. There was a tendency toward more major LARS in group A than in group B (46% vs 27%; P = 0.149). There was no difference in the mean GIQLI score between groups A and B (120 ± 16 vs 117 ± 19; P = 0.53) at the end of the follow-up period. Time after stoma closure (< 2 years) and previous radiotherapy were risk factors for major LARS in all populations.CONCLUSION: ICAA should be the procedure of choice where possible in redo surgery as it has better functional outcomes

Published
2020

24. Postoperative Peritonitis After Digestive Tract Surgery: Surgical Management and Risk Factors for Morbidity and Mortality, a Cohort of 191 Patients

Author

Thevy Hor, Clotilde Debove, Thomas Lescot, Najim Chafai, Ben Creavin, François Paye, Yann Parc, Thierry Bensignor, Jérémie H. Lefevre, Emmanuel Tiret, Pierre Balladur, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Service des Soins Intensifs [CHU Saint-Antoine]

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Perforation (oil well), Peritonitis, Anastomosis, Cohort Studies, Stoma, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, Humans, Medicine, Digestive System Surgical Procedures, Aged, Aged, 80 and over, Laparotomy, business.industry, Mortality rate, Surgical Stomas, 030208 emergency & critical care medicine, Perioperative, Middle Aged, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Cohort, Female, Morbidity, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study, Abdominal surgery
Abstract

International audience; BackgroundPostoperative peritonitis (POP) following gastrointestinal surgery is associated with significant morbidity and mortality, with no clear management option proposed. The aim of this study was to report our surgical management of POP and identify pre- and perioperative risk factors for morbidity and mortality.MethodsAll patients with POP undergoing relaparotomy in our department between January 2004 and December 2013 were included. Pre- and perioperative data were analyzed to identify predictors of morbidity and mortality.ResultsA total of 191 patients required relaparotomy for POP, of which 16.8% required >1 reinterventions. The commonest cause of POP was anastomotic leakage (66.5%) followed by perforation (20.9%). POP was mostly treated by anastomotic takedown (51.8%), suture with derivative stoma (11.5%), enteral resection and stoma (12%), drainage of the leak (8.9%), stoma on perforation (8.4%), duodenal intubation (7.3%) or intubation of the leak (3.1%). The overall mortality rate was 14%, of which 40% died within the first 48 h. Major complications (Dindo–Clavien > 2) were seen in 47% of the cohort. Stoma formation occurred in 81.6% of patients following relaparotomy. Independent risk factors for mortality were: ASA > 2 (OR = 2.75, 95% CI = 1.07–7.62, p = 0.037), multiorgan failure (MOF) (OR = 5.22, 95% CI = 2.11–13.5, p = 0.0037), perioperative transfusion (OR = 2.7, 95% CI = 1.05–7.47, p = 0.04) and upper GI origin (OR = 3.55, 95% CI = 1.32–9.56, p = 0.013). Independent risk factors for morbidity were: MOF (OR = 2.74, 95% CI = 1.26–6.19, p = 0.013), upper GI origin (OR = 3.74, 95% CI = 1.59–9.44, p = 0.0034) and delayed extubation (OR = 0.27, 95% CI = 0.14–0.55, p = 0.0027).ConclusionMortality following POP remains a significant issue; however, it is decreasing due to effective and aggressive surgical intervention. Predictors of poor outcomes will help tailor management options.

Published
2018

25. Identification of Positively and Negatively Selected Driver Gene Mutations Associated With Colorectal Cancer With Microsatellite Instability

Author

Agathe Guilloux, Sylvie Job, Nabila Elarouci, Olivier Buhard, Alex Duval, Thierry André, Lucile Armenoult, Mira Ayadi, Florence Coulet, Malorie Greene, Erell Guillerm, Anastasia R. Goloudina, Pascale Cervera, Toky Ratovomanana, Alain Virouleau, Samuel Landman, Yann Parc, Romane Bertrand, Vincent Jonchère, Aurélien de Reyniès, Magali Svrcek, Jérémie H. Lefevre, Sylvie Dumont, Fatiha Merabtene, Jean-François Fléjou, Laetitia Marisa, and Ada Collura

Subjects
bp, base pair, 0301 basic medicine, Genome instability, RTCA, Real-Time Cell Analyzer, Gene mutation, medicine.disease_cause, WES, whole-exome sequencing, Positive and Negative Selection, Negative selection, PCR, polymerase chain reaction, WGA, whole-genome amplification, Exome sequencing, Original Research, Mutation, Gastroenterology, MSI, microsatellite instability, indel, insertion/deletion, mRNA, messenger RNA, 3. Good health, UTR, untranslated region, Driver Gene Mutations, CRC, colorectal cancer, Colonic Neoplasms, shRNA, short hairpin RNA, MSH, MutS Homolog, Microsatellite, Microsatellite Instability, Tumorigenic Process, NR, nonrepetitive, PBS, phosphate-buffered saline, MMR, mismatch repair, Biology, R, repetitive, 03 medical and health sciences, RFS, relapse-free survival, medicine, Humans, lcsh:RC799-869, neoplasms, Colorectal Cancer, Hepatology, Microsatellite instability, medicine.disease, HR, hazard ratio, digestive system diseases, 030104 developmental biology, Attitude, siRNA, small interfering RNA, Cancer research, lcsh:Diseases of the digestive system. Gastroenterology, MLH1, MutL Homolog 1, Carcinogenesis
Abstract

Background & Aims Recent studies have shown that cancers arise as a result of the positive selection of driver somatic events in tumor DNA, with negative selection playing only a minor role, if any. However, these investigations were concerned with alterations at nonrepetitive sequences and did not take into account mutations in repetitive sequences that have very high pathophysiological relevance in the tumors showing microsatellite instability (MSI) resulting from mismatch repair deficiency investigated in the present study. Methods We performed whole-exome sequencing of 47 MSI colorectal cancers (CRCs) and confirmed results in an independent cohort of 53 MSI CRCs. We used a probabilistic model of mutational events within microsatellites, while adapting pre-existing models to analyze nonrepetitive DNA sequences. Negatively selected coding alterations in MSI CRCs were investigated for their functional and clinical impact in CRC cell lines and in a third cohort of 164 MSI CRC patients. Results Both positive and negative selection of somatic mutations in DNA repeats was observed, leading us to identify the expected true driver genes associated with the MSI-driven tumorigenic process. Several coding negatively selected MSI-related mutational events (n = 5) were shown to have deleterious effects on tumor cells. In the tumors in which deleterious MSI mutations were observed despite the negative selection, they were associated with worse survival in MSI CRC patients (hazard ratio, 3; 95% CI, 1.1–7.9; P = .03), suggesting their anticancer impact should be offset by other as yet unknown oncogenic processes that contribute to a poor prognosis. Conclusions The present results identify the positive and negative driver somatic mutations acting in MSI-driven tumorigenesis, suggesting that genomic instability in MSI CRC plays a dual role in achieving tumor cell transformation. Exome sequencing data have been deposited in the European genome–phenome archive (accession: EGAS00001002477)., Graphical abstract

Published
2018

27. Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency

Author

Rachid Kaci, Magali Svrcek, Dewi Vernerey, Pascale Cervera, Alex Duval, Philippe Bertheau, Yann Parc, Sylvie Dumont, Thierry André, Frédéric Bibeau, Romain Cohen, Daniel Lopez-Trabada, Jean-Marc Gornet, J-B. Bachet, Armelle Bardier, Elisabeth Hain, Olivier Buhard, Florence Renaud, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastroentérologie, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Service de chirurgie générale et digestive [CHU Saint-Antoine], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Oncologie Médicale [CHU Saint -Antoine], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'Oncologie Médicale [CHU Saint-Antoine]

Subjects
Male, 0301 basic medicine, Cancer Research, Heredity, Time Factors, Colorectal cancer, Kaplan-Meier Estimate, DNA Mismatch Repair, 0302 clinical medicine, Risk Factors, PMS2, Neoplasm Metastasis, Middle Aged, Lynch syndrome, Pedigree, 3. Good health, Phenotype, Treatment Outcome, Molecular Diagnostic Techniques, Oncology, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, DNA mismatch repair, France, Colorectal Neoplasms, MutL Protein Homolog 1, Adult, Proto-Oncogene Proteins B-raf, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, Disease-Free Survival, Diagnosis, Differential, 03 medical and health sciences, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Predictive Value of Tests, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, neoplasms, Aged, Proportional Hazards Models, Retrospective Studies, nutritional and metabolic diseases, Cancer, Microsatellite instability, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, DNA Methylation, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 030104 developmental biology, Multivariate Analysis, Mutation, Cancer research
Abstract

International audience; Background: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs.Patients and methods: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation.Results: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (31%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44).Conclusions: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

Published
2017

28. Total midgut volvulus in adults with intestinal malrotation. Report of eleven patients

Author

H. Kotobi, Yann Parc, Jérémie H. Lefevre, F Duramé, G Audry, and V Tan

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Operative Time, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Laparoscopy, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, General surgery, Retrospective cohort study, Pediatric Surgeon, General Medicine, Length of Stay, Middle Aged, Short bowel syndrome, medicine.disease, Surgery, Volvulus, Intestines, Treatment Outcome, Elective Surgical Procedures, Intestinal malrotation, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, Elective Surgical Procedure, business, Digestive System Abnormalities, Follow-Up Studies, Intestinal Volvulus, Abdominal surgery
Abstract

Summary Objective Total small-intestinal volvulus with malrotation (TSIVM) classically presents in the neonatal period; it occurs much less frequently in the adult and is often misdiagnosed. Prognosis is directly related to the degree and duration of intestinal ischemia. Our goal is to describe our experience with TSIVM in the adult, to identify any specific findings and to discuss its management. Method Eleven patients who had undergone surgery for TSIVM at three centers between 1992 and 2012 were included. Surgery was performed as an emergency for five patients and surgery was elective for six. Results Mean follow-up was 63 months (range: 12–270). Six patients had had previous abdominal surgery. In nine cases, the diagnosis of TSIVM was made preoperatively, mainly by CT scan in eight cases. Seven patients had associated congenital failure of retroperitoneal fixation of the right colon and all of these underwent a Ladd procedure. The mortality rate was zero. Of the five patients who underwent emergency surgery, three required intestinal resections, one of whom developed a short bowel syndrome. The six patients who underwent surgery electively had no surgical complications. Conclusion TSIVM is a very unusual finding in adult patients. The diagnosis can be made by CT scan with IV and oral contrast, but it often comes to light only at the time of surgery, even though the patients have often had recurrent episodes of abdominal symptomatology that dated back to childhood. The Ladd procedure, consisting of division of Ladd's bands, widening of the mesentery, and incidental appendectomy, remains the standard surgical repair. Digestive surgeons who care for adults should be familiar with this procedure, and it should be performed, as often as possible, with the assistance of a pediatric surgeon.

Published
2017

29. Immunotherapy and patients treated for cancer with microsatellite instability

Author

Daniel Lopez-Trabada, Isabelle Trouilloud, Yann Parc, Olivier Lascols, Thierry André, Jean-François Fléjou, Magali Svrcek, Alex Duval, Romain Cohen, Delphine Cochereau, Jérémie H. Lefevre, Raphael Colle, and Pauline Afchain

Subjects
Male, 0301 basic medicine, Oncology, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Biology, Polymerase Chain Reaction, 03 medical and health sciences, 0302 clinical medicine, Neoplastic Syndromes, Hereditary, Stomach Neoplasms, Neoplasms, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, neoplasms, Brain Neoplasms, Endometrial cancer, nutritional and metabolic diseases, Cancer, Microsatellite instability, Cell Cycle Checkpoints, Sequence Analysis, DNA, Hematology, General Medicine, Immunotherapy, medicine.disease, Immunohistochemistry, digestive system diseases, Lynch syndrome, Immune checkpoint, Endometrial Neoplasms, 3. Good health, Phenotype, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, DNA mismatch repair, Colorectal Neoplasms
Abstract

Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors.

Published
2017

30. A Scoring System to Determine Patients' Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis

Author

Guillaume Le Baut, Julien Kirchgesner, Aurélien Amiot, Jérémie H. Lefevre, Najim Chafai, Cécilia Landman, Isabelle Nion, Anne Bourrier, Charlotte Delattre, Chloé Martineau, Harry Sokol, Phillipe Seksik, Yann Nguyen, Yoann Marion, Gil Lebreton, Franck Carbonnel, Stéphanie Viennot, Laurent Beaugerie, Lionel Arrive, Marine Camus, Ulriikka Chaput, Laurence Cholley Monnier, Clotilde Debove, Xavier Dray, Jean-François Fléjou, Guillaume Le Gall, Nadia Hoyeau, Cecilia Landman, Philippe Marteau, Isabelle Nion-Larmurier, Violaine Ozenne, Yann Parc, Philippe Seksik, Magali Svrcek, and Emmanuel Tiret

Subjects
medicine.medical_specialty, medicine.medical_treatment, Inflammatory bowel disease, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Colectomy, Retrospective Studies, Hepatology, biology, business.industry, Hazard ratio, C-reactive protein, Gastroenterology, medicine.disease, Ulcerative colitis, Confidence interval, Hospitals, 3. Good health, Hospitalization, 030220 oncology & carcinogenesis, Cohort, biology.protein, 030211 gastroenterology & hepatology, Colitis, Ulcerative, business
Abstract

Background & Aims There is consensus on the criteria used to define acute severe ulcerative colitis (ASUC) and on patient management, but it has been a challenge to identify patients at risk for colectomy based on data collected at hospital admission. We aimed to develop a system to determine patients’ risk of colectomy within 1 y of hospital admission for ASUC based on clinical, biomarker, and endoscopy data. Methods We performed a retrospective analysis of consecutive patients with ASUC treated with corticosteroids, ciclosporin, or tumor necrosis factor (TNF) antagonists and admitted to 2 hospitals in France from 2002 through 2017. Patients were followed until colectomy or loss of follow up. A total of 270 patients with ASUC were included in the final analysis, with a median follow-up time of 30 months (derivation cohort). Independent risk factors identified by Cox multivariate analysis were used to develop a system to identify patients at risk for colectomy 1 y after ASUC. We developed a scoring system based on these 4 factors (1 point for each item) to identify high-risk (score 3 or 4) vs low-risk (score 0) patients. We validated this system using data from an independent cohort of 185 patients with ASUC treated from 2006 through 2017 at 2 centers in France. Results In the derivation cohort, the cumulative risk of colectomy was 12.3% (95% CI, 8.6–16.8). Based on multivariate analysis, previous treatment with TNF antagonists or thiopurines (hazard ratio [HR], 3.86; 95% CI, 1.82–8.18), Clostridioides difficile infection (HR, 3.73; 95% CI, 1.11–12.55), serum level of C-reactive protein above 30 mg/L (HR, 3.06; 95% CI, 1.11–8.43), and serum level of albumin below 30 g/L (HR, 2.67; 95% CI, 1.20–5.92) were associated with increased risk of colectomy. In the derivation cohort, the cumulative risks of colectomy within 1 y in patients with scores of 0, 1, 2, 3, or 4 were 0.0%, 9.4% (95% CI, 4.3%–16.7%), 10.6% (95% CI, 5.6%–17.4%), 51.2% (95% CI, 26.6%–71.3%), and 100%. Negative predictive values ranged from 87% (95% CI, 82%–91%) to 92% (95% CI, 88%–95.0%). Findings from the validation cohort were consistent with findings from the derivation cohort. Conclusions We developed a scoring system to identify patients at low-risk vs high-risk for colectomy within 1 y of hospitalization for ASUC, based on previous treatment with TNF antagonists or thiopurines, C difficile infection, and serum levels of CRP and albumin. The system was validated in an external cohort.

Published
2019

31. Ten-year impact of pancreaticoduodenectomy on bowel function and quality of life of patients with ileal pouch-anal anastomosis for familial adenomatous polyposis

Author

Pierre Balladur, François Paye, Thibault Voron, Omar Ahmed, Yann Parc, Jérémie H. Lefevre, M. Collard, and Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030230 surgery, Anastomosis, Gastroenterology, Familial adenomatous polyposis, Pancreaticoduodenectomy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Diabetes mellitus, Internal medicine, medicine, Humans, Bowel function, Hepatology, business.industry, Anastomosis, Surgical, Proctocolectomy, Restorative, medicine.disease, 3. Good health, Ileal Pouch Anal Anastomosis, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Quality of Life, business
Abstract

Background Patients with familial adenomatous polyposis (FAP) carry a risk of duodenal adenocarcinoma. These patients, who already have an ileal pouch-anal anastomosis (IPAA), sometimes require pancreaticoduodenectomy (PD). This work aims to evaluate the long-term consequences of the combination of PD + IPAA. Methods All patients with IPAA due to FAP who underwent PD from 1991 to 2017 were included (PD + IPAA group). Patients were matched 1:1 according to age, sex, ASA score and presence of colorectal cancer. Fecal continence and quality of life (QoL) were assessed using the Wexner score and the EORTC-QLQ-C30 questionnaire. Results Thirty-two PD + IPAA patients were matched with thirty-two IPAA-only patients. In each group, the response rate to the questionnaire was 78% (25/32). No differences were noted between PD + IPAA and IPAA-only groups in terms of daytime fecal frequency (6.0 vs 6.0; p = 0.362), Wexner score (3/20 vs 4/20; p = 0.984) and global QoL score (83.3/100 vs 83.3/100; p = 0.401). In the PD + IPAA group, 26% of patients developed diabetes a median period of 10.0 years after PD. The global QoL for these patients was significantly altered (p = 0.011), while daytime fecal frequency was unaffected (p = 0.092) as fecal continence (p = 0.475). Conclusion In FAP patients with IPAA, PD does not affect bowel function or QoL.

Published
2019

32. Martius advancement flap for low rectovaginal fistula (with video)

Author

J. Nguyen, Yann Parc, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Adult, medicine.medical_specialty, business.industry, Fistula, [SDV]Life Sciences [q-bio], Rectovaginal Fistula, General Medicine, medicine.disease, Delivery, Obstetric, Surgical Flaps, Surgery, 03 medical and health sciences, 0302 clinical medicine, Rectovaginal fistula, 030220 oncology & carcinogenesis, medicine, Humans, 030211 gastroenterology & hepatology, Female, business
Published
2019

33. Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

Author

Yann Parc, Isabelle Coupier, Erell Guillerm, Jerôme Bellanger, Aurélie Maran Gonzalez, Magali Svrcek, Jeanne Netter, Jérôme Alexandre Denis, Chrystelle Colas, Mathilde Warcoin, A. Mourregot, Mohamed Zizi, Florent Soubrier, Florence Coulet, Axelle Canard, Mélanie Eyries, Hélène Delhomelle, Véronica Cusin, Patrick R. Benusiglio, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Curie [Paris], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Sorbonne Université (SU), Institut du Cancer de Montpellier (ICM), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, Cancer Research, medicine.medical_treatment, medicine.disease_cause, Gastroenterology, Germline, 0302 clinical medicine, Surgical oncology, Mutation, General Medicine, Middle Aged, Prognosis, 3. Good health, Pedigree, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Hereditary diffuse gastric cancer, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Germline mutation, Gastrectomy, Stomach Neoplasms, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Germ-Line Mutation, Retrospective Studies, Diffuse gastric cancer, CDH1, business.industry, Signet-ring cell, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Hereditary cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Asymptomatic Diseases, CTNNA1, business, Asymptomatic carrier, Carcinoma, Signet Ring Cell, alpha Catenin, Follow-Up Studies
Abstract

International audience; In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

Published
2019

34. What is the functional result of a delayed coloanal anastomosis in redo rectal surgery?

Author

Clotilde Debove, Hortense Boullenois, Mélanie Calmels, Thibault Voron, Yann Parc, Jérémie H. Lefevre, Ben Creavin, Najim Chafai, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Sorbonne Université (SU)

Subjects
Male, Babcock procedure, Fistula, Anal Canal, 030230 surgery, Cohort Studies, Postoperative Complications, 0302 clinical medicine, Quality of life, Interquartile range, Rectal surgery, Coloanal anastomosis, Proctectomy, Anastomosis, Surgical, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Pelvic Inflammatory Disease, Adult, Reoperation, medicine.medical_specialty, coloanal anastomosis, Colon, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Anastomosis, Risk Assessment, Time-to-Treatment, Stoma, 03 medical and health sciences, Sepsis, medicine, Humans, In patient, Aged, Retrospective Studies, Rectal Neoplasms, business.industry, Rectovaginal Fistula, Surgical Stomas, redo surgery, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Surgery, Quality of Life, delayed anastomosis, business, Follow-Up Studies
Abstract

International audience; BACKGROUND: Delayed coloanal anastomosis (DCAA) may be used in patients with complex rectal conditions, such as chronic pelvic sepsis, low recto-vaginal and recto-vesical fistula; however, limited data are available. The aim is to report the morbidity and functional results of DCAA in redo rectal surgery.METHODS: All patients undergoing DCAA between January 2014 and August 2017 were retrospectively included. Success was defined as a functional anastomosis without stoma, evaluated using the Low Anterior Resection Syndrome (LARS) score and the Gastrointestinal Quality of Life Index (GIQLI) functional assessment tools.RESULTS: Of the 72 redo pelvic surgeries, 29 (40.3%) DCAA were performed over a 4-year period. Indications for redo resection were chronic pelvic sepsis (n = 13, 44.8%), recto-vaginal fistula (n = 11, 37.9%) and recto-vesical fistula (n = 5, 17.2%). Mean interval period between the two procedures was 14 ± 3 days (8-21). Global major morbidity (Clavien-Dindo III or IV) was seen in six patients (20.7%). Stoma closure was feasible for 22 (75.9%) patients after a median period of 78 days (interquartile range 61-98). The 6-month success rate was 79.3%. Mean LARS was 28.8 ± 10.2 (3-41) (minor LARS) for 18 patients with no stoma at the end of follow-up. LARS score was significantly better with a follow-up >2 years (23.3 ± 12.2 versus 32.3 ± 7.9), P = 0.074. Mean GIQLI score was 79.2 ± 14.3 (48-98).CONCLUSIONS: Transanal colonic pull through with delayed anastomosis for redo-surgery in complex pelvic situations had low morbidity and avoided a permanent stoma in three out of four patients with an acceptable quality of life.

Published
2019

35. Lynch syndrome: What is new?

Author

Florence Coulet, Jeanne Netter, Anna Pellat, Magali Svrcek, Romain Cohen, Thierry André, Alex Duval, Yann Parc, Géraldine Perkins, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Instabilité des microsatellites et cancers [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de chirurgie générale et digestive [CHU Saint-Antoine], and Service d'Anatomopathologie [CHU Saint-Antoine]

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Colorectal cancer, Immunothérapie, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer colorectal, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Epigenetics, neoplasms, Syndrome de Lynch, business.industry, Endometrial cancer, Cancer, Microsatellite instability, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hematology, General Medicine, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, 16. Peace & justice, medicine.disease, Lynch syndrome, digestive system diseases, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, DNA mismatch repair, Immunotherapy, business
Abstract

International audience; Lynch syndrome is a genetic condition defined by a germline mutation of an MMR (MisMatch Repair) gene leading to a defective DNA MMR system. Therefore, it is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer (CRC) and endometrial cancer (EC). Lynch syndrome-related CRC accounts for 3% of all CRC. Lynch syndrome also accounts for 2% of all EC. In case of Lynch syndrome, there is usually a familial history of cancer defined by the Amsterdam and Bethesda criteria. Diagnosis is made by tumor testing with (i) MMR immunohistochemistry and (ii) PCR for MSI (microsatellite instability), a genetic phenotype that characterizes these tumors. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system. Progress in diagnosis and molecular biology has allowed for better identification of Lynch patients but also other rare genetic syndromes. MSI tumors can now benefit from new treatments such as immunotherapy which underlines the importance of their diagnosis. Finally, patients with Lynch syndrome as well as their relatives, undergo specific surveillance in order to prevent development of other cancers. This review will summarize the different aspects of Lynch syndrome and also focus on recent progress on the topic.

Published
2019

36. 46P [18F]2-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18FDG-PET/CT) in patients treated with immune checkpoint inhibitors (ICI) for microsatellite instability-high metastatic colorectal cancer (MSI mCRC)

Author

Thibault Mazard, David Tougeron, F. Montravers, Magali Svrcek, M-L. Garcia-Larnicol, Yves Menu, Yann Parc, T. Pudlarz, T. Andre, E. Kempf, Benoist Chibaudel, Régis Cohen, J. Bennouna, C. de la Fouchardiere, and Christophe Borg

Subjects
Colorectal cancer, business.industry, Immune checkpoint inhibitors, 18f 2 fluoro 2 deoxy d glucose, Microsatellite instability, Hematology, medicine.disease, 18fdg pet ct, Oncology, Cancer research, medicine, In patient, business, Positron Emission Tomography-Computed Tomography
Published
2020

37. Management of postoperative bladder emptying after proctectomy in men for rectal cancer. A retrospective study of 190 consecutive patients

Author

N. Chafai, Jérémie H. Lefevre, Yann Parc, Malika Bennis, Cécile Bouchet-Doumenq, Emmanuel Tiret, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Adult, Male, urinary dysfunction, medicine.medical_specialty, Urinary system, media_common.quotation_subject, Urinary Bladder, Urination, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Catheterization, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, transurethral catheterization, medicine, Humans, rectal cancer, Coloanal anastomosis, Device Removal, Digestive System Surgical Procedures, Aged, Retrospective Studies, colorectal anastomosis, media_common, Aged, 80 and over, Urinary bladder, Rectal Neoplasms, Urinary retention, business.industry, Gastroenterology, Retrospective cohort study, Middle Aged, Total mesorectal excision, 3. Good health, Surgery, Catheter, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Multivariate Analysis, Drainage, 030211 gastroenterology & hepatology, medicine.symptom, suprapubic catheterization, business
Abstract

International audience; PurposeEvaluation of urinary drainage after rectal resection and identification of criteria associated with postoperative urinary dysfunction (UD). UD remains a clinical problem for up to two thirds of patients after rectal resection. Currently, there are no guidelines concerning duration or type of drainage.MethodsOne hundred ninety consecutive rectal resections (abdomino-perineal resection (APR = 47), mechanical coloanal anastomosis (MechCAA = 48), manual coloanal anastomosis (ManCAA = 47), colorectal anastomosis (CRA = 48)) in male patients were included. In patients with a transurethral catheterization (TUC), the drainage was removed at day 5. Patients with a suprapubic catheterization (SPC) underwent drainage removal according to the results of a clamping test at day 5. UD was defined as drainage removal after day 6 and/or acute urinary retention (AUR).ResultsDrainage types were SPC (n = 136, 72 %) and TUC (n = 54, 28 %). SPC was used more frequently after total mesorectal excision (TME) (APR, ManCAA, MechCAA) (83–92 %). Complications rates of SPC and TUC were 20 and 9 %. The clamping test was positive for 61 patients (48 %), and SPC was removed before/on POD6 without any episode of AUR. After TUC removal, two patients (4 %) had AUR. Seventy-two (38 %) patients had UD: 11 (6 %) were discharged with an indwelling catheter, and in 61 (32 %), the catheter was removed after day6. Three independent factors were associated with UD: diabetes (OR = 2.9 (1.2–7.7)), urological history (OR = 2.9 (1.2–7.6)), and TME (OR = 5.2 (2.3–13.5)).ConclusionThe UD rate after surgery for rectal cancer was 38 %. The clamping test is accurate to prevent AUR after SPC removal. The three risk factors may serve to select good candidates for early catheter removal.

Published
2015

38. Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients

Author

Chrystelle Colas, Carolina Bonilla, Yann Parc, Jérémie H. Lefevre, Katarzyna Hutnik, Elaine C. Johnstone, Abdelhamid Boumertit, Rachel Midgley, Susan Tonks, Tammy Day, David J. Kerr, Walter F. Bodmer, and Bruce Winney

Subjects
Oncology, Adenoma, Adult, Male, medicine.medical_specialty, Candidate gene, Colorectal cancer, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Neoplasms, Multiple Primary, Gene Frequency, Internal medicine, Genetics, medicine, Humans, Cyclin D1, Age of Onset, Allele frequency, Genetics (clinical), Case-control study, Cancer, Odds ratio, Middle Aged, medicine.disease, United Kingdom, Case-Control Studies, Female, France, Age of onset, Colorectal Neoplasms
Abstract

We examined the influence that rare variants and low-frequency polymorphisms in the cancer candidate gene CCND1 have on the development of multiple intestinal adenomas and the early onset of colorectal cancer. Individuals with

Published
2018

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

Author

Thomas Aparicio, Emmanuelle Samalin, Pierre Michel, Olivier Bouché, Blaise Batumona, Laurent Bedenne, Christophe Cellier, Benoit Chibaudel, Yves Becouarn, Marc Pocard, Yann Parc, Pauline Afchain, Nicolas Carrere, Christophe Locher, Centre Hospitalier de Meaux, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Purpan (CHU Purpan), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Rouen, Normandie Université (NU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-APHP, Institut hospitalier Franco-Britannique [Levallois-Perret], and Centre Hospitalier Universitaire de Reims (CHU Reims)

Subjects
medicine.medical_specialty, Colorectal cancer, Small bowel adenocarcinoma, Colonoscopy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Adenocarcinoma, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Intestinal Neoplasms, Intestine, Small, National recommendations, medicine, Humans, Stage (cooking), Intersectoral Collaboration, Neoplasm Staging, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Cancer, Platinum salts, medicine.disease, 3. Good health, Surgery, Clinical Practice, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, 030211 gastroenterology & hepatology, France, business
Abstract

IF 3.061; International audience; BackgroundThis document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016.MethodThis 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).ResultsSmall 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).ConclusionFew 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.

Published
2018

40. Does transanal local resection increase morbidity for subsequent total mesorectal excision for early rectal cancer?

Author

Yann Parc, Clotilde Debove, Ben Creavin, Jérémie H. Lefevre, C. Coton, Najim Chafai, Emmanuel Tiret, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université de Rennes (UR), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)

Subjects
Male, Reoperation, transanal endoscopic microsurgery, medicine.medical_specialty, Abdominal Abscess, Colorectal cancer, medicine.medical_treatment, Anastomotic Leak, morbidity, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Anastomosis, Adenocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, medicine, Rectal Adenocarcinoma, Humans, Surgical Wound Infection, Mesentery, early rectal cancer, Mesorectal, Aged, Retrospective Studies, Transanal Endoscopic Surgery, 2. Zero hunger, Transanal Excision, Proctectomy, business.industry, Rectal Neoplasms, total mesorectal excision, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, local excision, Microsurgery, Length of Stay, Middle Aged, medicine.disease, Total mesorectal excision, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Case-Control Studies, 030211 gastroenterology & hepatology, Female, business, Body mass index
Abstract

International audience; AIM: Local excision is recommended for early rectal cancer (pT1). Complementary total mesorectal excision (cTME) is warranted when bad pathological features are present. The impact of a prior local resection on the outcome remains unclear. The aim of this study was to assess if prior local excision increases the morbidity of a subsequent cTME compared with primary TME.METHODS: From 2001 to 2016 all patients who underwent TME after local excision for rectal adenocarcinoma were studied. All were matched (1:1) with patients who underwent primary TME, without neoadjuvant radiochemotherapy. The matching factors included age, sex, body mass index, American Society of Anesthesiologists score and type of surgery. Short-term morbidity and pathological examination of the resected specimen were compared.RESULTS: Forty-one patients were included (14 women, 34%, mean age 65 ± 11 years), comprising classic transanal excision (66%) and transanal endoscopic microsurgery (34%), and were matched to 41 patients who had primary TME. cTME was significantly longer (315 min ± 87 vs 275 min ± 58, P = 0.03). The overall morbidity was 48.8% in the local excision group vs 31.7% in the control group (P = 0.18). Surgical morbidity was 31.7% vs 26.8% (P = 0.8). Anastomotic related morbidity was similar (local excision 17% vs TME 14.6%, P = 0.84) and the mean length of stay was similar (14 days) in both groups. There was a tendency to a worse quality of mesorectal excision in the cTME group (17% vs 5%, P = 0.15).CONCLUSION: Local excision prior to TME for early rectal cancer tends to increase overall morbidity and may worsen the quality of the mesorectal plane but should be considered as a surgical approach in select cases.

Published
2018

41. Postoperative Morbidity Risks Following Ileocolic Resection for Crohn's Disease Treated With Anti-TNF Alpha Therapy: A Retrospective Study of 360 Patients

Author

Yann Parc, Najim Chafai, Laurent Beaugerie, Ingrid Jouvin, Sophie Pitel, Jérémie H. Lefevre, Emmanuel Tiret, and Ben Creavin

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Subgroup analysis, Preoperative care, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Postoperative Complications, Crohn Disease, Recurrence, Risk Factors, medicine, Immunology and Allergy, Humans, Risk factor, Laparoscopy, Colectomy, Retrospective Studies, Crohn's disease, medicine.diagnostic_test, business.industry, Ileostomy, Tumor Necrosis Factor-alpha, Mortality rate, Anastomosis, Surgical, Gastroenterology, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Surgery, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, business
Abstract

Background Despite the effectiveness of anti-TNF alpha (ATA) treatment to induce and maintain remission in Crohn's disease, surgical intervention is frequently required. Results of previous studies on the impact of anti-TNF on postoperative course are discordant. The aim of this study was to evaluate the impact of ATA on postoperative morbidity following ileocolic resection for Crohn's disease. Methods A retrospective review of Crohn's disease patients undergoing ileocolic resection was performed. Patients receiving medical treatment ≤8 weeks prior to surgery were included and followed up for postoperative morbidity. The Clavien-Dindo classification was used for grading complications. Risk factors for postoperative morbidity were assessed on multivariable analysis. Results A total of 360 patients underwent ileocolic resection for Crohn's disease between 2002 and 2013; 15.3% of patients had ATA ≤8 weeks prior to surgery. Laparoscopic resections were performed in 110 cases (31%), of which 6% were converted to an open operation. Primary anastomosis without the formation of a diverting ileostomy was performed in 301 cases. Overall morbidity was 24.2%, with a mortality rate of 0.8%. ATA use prior to surgery was identified as an independent risk factor for overall morbidity (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.08-3.82; P = 0.027) and septic complications (OR, 2.14; 95% CI, 1.03-4.29; P = 0.04). In subgroup analysis of patients with a primary anastomosis, ATA use had no significant impact on septic or overall morbidity. Conclusions Preoperative ATA use is a risk factor for overall postoperative morbidity and septic complications. However, the formation of a primary anastomosis should not be influenced by preoperative ATA use.

Published
2017

42. Ladd procedure for malrotation with total intestinal volvulus

Author

V Tan, Yann Parc, and H Kotobi

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Treatment outcome, Abdominal cavity, Risk Assessment, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Intestinal Volvulus, Laparotomy, Severity of illness, medicine, Intubation, Humans, Mesentery, Laparoscopy, Intubation, Gastrointestinal, Postoperative Care, medicine.diagnostic_test, business.industry, Abdominal Cavity, General Medicine, Recovery of Function, Surgery, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, business
Published
2017

43. The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors

Author

Côme Lepage, Thierry André, Dominique Guenot, Alex Duval, Kristell Wanherdrick, Etienne Becht, Janick Selves, Yann Parc, Valentin Derangère, François Ghiringhelli, Jean-François Fléjou, Vincent Jonchère, Anastasia R. Goloudina, Romain Cohen, Pierre Laurent-Puig, Sylviane Olschwang, Pascale Cervera, Chrystelle Colas, Valérie Boige, Laetitia Marisa, Ada Collura, Magali Svrcek, Gérard Milano, Olivier Buhard, Jérémie H. Lefevre, Aurélien de Reyniès, Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Pathologies biliaires, fibrose et cancer du foie ( Inserm UMR_S 938 ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Service d'Anatomie Pathologique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Développement et physiopathologie de l'intestin et du pancréas, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Oncologie Médicale [CHU Saint -Antoine], Service d'Oncogénétique et Angiogénétique Moléculaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie générale et digestive [CHU Saint-Antoine], UMR S775, Université Paris Descartes - Paris 5 ( UPD5 ), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ), Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie [Hôpital Clairval - Marseille], Hôpital Privé Clairval [Marseille], Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Paris Descartes - Paris 5 (UPD5), Institut Gustave Roussy (IGR), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Unité fonctionnelle d'Oncogénétique et Angiogénétique Moléculaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Lymphocyte, Programmed Cell Death 1 Receptor, neoplasms, Gene Expression, B7-H1 Antigen, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, t-lymphocyte, CTLA-4 Antigen, programmed cell death 1 ligand 1, genes, Hepatitis A Virus Cellular Receptor 2, colonic neoplasms, Middle Aged, Prognosis, Lymphocyte Activation Gene 3 Protein, 3. Good health, Survival Rate, medicine.anatomical_structure, 030220 oncology & carcinogenesis, cytotoxicity, Female, Microsatellite Instability, cell cycle checkpoint, Colorectal Neoplasms, medicine.medical_specialty, Colon, T cell, CD8 Antigens, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, lymphocyte, patient prognosis, Inducible T-Cell Co-Stimulator Protein, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Antigens, CD, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival rate, Neoplasm Staging, Retrospective Studies, business.industry, Proportional hazards model, Microsatellite instability, Th1 Cells, medicine.disease, Programmed Cell Death 1 Ligand 2 Protein, Immune checkpoint, digestive system diseases, 030104 developmental biology, consensus, business, CD8, T-Lymphocytes, Cytotoxic
Abstract

IF 12.589; International audience; BackgroundImmune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore.MethodsThe expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided.ResultsThe expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004).ConclusionsICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.

Published
2016

44. HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer

Author

Coralie Dorard, Richard Hamelin, Kristell Wanherdrick, Magali Svrcek, Anne-Marie Bouvier, Pascale Cervera, Mouna Chouchène, Yann Parc, Anaïs Lagrange, Chrystelle Colas, Florence Coulet, Richie Soong, Carmen Garrido, Jérémie H. Lefevre, Janick Selves, Alex Duval, Erell Guillerm, Olivier Lascols, Sahra Bodo, Thierry André, Laetitia Marisa, Jean-François Fléjou, Ada Collura, Côme Lepage, Olivier Buhard, Kerryn Garrett, Caroline Chapusot, Marie-Pierre Gaub, A’dem Bokhari, Barry Iacopetta, Malorie Greene, Isabelle Sourouille, Agathe Guilloux, Martine Muleris, Hélène Blanché, Nizar El-Murr, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École polytechnique (X), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fondation Jean Dausset CEPH, Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), National University of Singapore (NUS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Développement et physiopathologie de l'intestin et du pancréas, Institut National de la Santé et de la Recherche Médicale (INSERM), St John God HealthCare, The University of Western Australia (UWA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service de chirurgie générale et digestive [CHU Saint-Antoine], National University of Singapore - Cancer Science Institute of Singapore, Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Service d'Oncologie Médicale [CHU Saint -Antoine], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), École polytechnique ( X ), (le programme) Cartes d'identité des tumeurs ( CIT ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), National University of Singapore ( NUS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), The University of Western Australia ( UWA ), and Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL )

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Genotype, Colorectal cancer, Population, Mismatch Repair, Biology, Guidelines, Bioinformatics, DNA Mismatch Repair, Colon-Cancer, 03 medical and health sciences, 0302 clinical medicine, Molecular genetics, Internal medicine, Diagnostic-Tests, Genetics, medicine, Biomarkers, Tumor, Humans, Chemotherapy, HSP110 Heat-Shock Proteins, education, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genotyping, neoplasms, Genetics (clinical), Tumors, education.field_of_study, Pentaplex Pcr, Microsatellite instability, DNA, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, digestive system diseases, 3. Good health, Mononucleotide Repeats, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, DNA mismatch repair, Microsatellite Instability, Lynch-Syndrome, Colorectal Neoplasms, Mutations
Abstract

IF 5.65; International audience; Background Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI, a marker for defective DNA mismatch repair) as a first screen for Lynch syndrome (LS). In this study, we investigated whether it may be possible to improve the detection of MSI in CRC. We examined whether the HT17 DNA repeat (critical for correct splicing of the chaperone HSP110) might constitute a superior marker for diagnosis of the MSI phenotype in patients with CRC compared with the standard panel of markers (pentaplex).Methods The HT17 polymorphism was analysed in germline DNA from 1037 multi-ethnic individuals. We assessed its sensitivity and specificity for detecting MSI in a multicentre, population-based cohort of 685 patients with CRC and an additional series of 70 patients with CRC considered to be at-risk of LS. All cases were screened earlier for MSI using pentaplex markers. Cases showing discordant HT17/pentaplex results were further examined for the expression of mismatch repair proteins.Results HT17 status was analysed independently and blinded to previous results from pentaplex genotyping. HT17 showed no germline allelic variation outside a very narrow range. Compared with the pentaplex panel, HT17 showed better sensitivity (0.984 (95% CI 0.968 to 0.995) vs 0.951 (95% CI 0.925 to 0.972)) and similar specificity (0.997 (95% CI 0.989 to 1.000) for both) for the detection of MSI. Furthermore, HT17 alone correctly classified samples judged to be uncertain with the pentaplex panel and showed excellent ability to detect MSI in patients with LS.Conclusions HT17 simplifies and improves the current standard molecular methods for detecting MSI in CRC.

Published
2016

45. Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study

Author

Sheraz R. Markar, Caroline Gronnier, Arnaud Pasquer, Alain Duhamel, Hélène Beal, Jérémie Théreaux, Johan Gagnière, Gil Lebreton, Cécile Brigand, Bernard Meunier, Denis Collet, Christophe Mariette, Abdennahceur Dhahri, Delphine Lignier, Cyril Cossé, Jean-Marc Regimbeau, Magalie Cabau, Jacques Jougon, Bogdan Badic, Patrick Lozach, Jean Pierre Bail, Serge Cappeliez, Issam El Nakadi, Arnaud Alves, Renaud Flamein, Denis Pezet, Federica Pipitone, Bogdan Stan-Iuga, Nicolas Contival, Eric Pappalardo, Simon Msika, Styliani Mantziari, Nicolas Demartines, Flora Hec, Marguerite Vanderbeken, Williams Tessier, Nicolas Briez, Fabien Fredon, Alain Gainant, Muriel Mathonnet, Jean Marc Bigourdan, Salim Mezoughi, Christian Ducerf, Jacques Baulieux, Jean-Yves Mabrut, Oussama Baraket, Gilles Poncet, Mustapha Adham, Delphine Vaudoyer, Peggy Jourdan Enfer, Laurent Villeneuve, Olivier Glehen, Thibault Coste, Jean-Michel Fabre, Frédéric Marchal, Romain Frisoni, Ahmet Ayav, Laurent Brunaud, Laurent Bresler, Charlotte Cohen, Olivier Aze, Nicolas Venissac, Daniel Pop, Jérôme Mouroux, Ion Donici, Michel Prudhomme, Emanuele Felli, Stéphanie Lisunfui, Marie Seman, Gaelle Godiris Petit, Mehdi Karoui, Christophe Tresallet, Fabrice Ménégaux, Jean-Christophe Vaillant, Laurent Hannoun, Brice Malgras, Denis Lantuas, Karine Pautrat, Marc Pocard, Patrice Valleur, Najim Chafai, Pierre Balladur, Magalie Lefrançois, Yann Parc, François Paye, Emmanuel Tiret, Marius Nedelcu, Letizia Laface, Thierry Perniceni, Brice Gayet, Alexandre Filipello, Jack Porcheron, Olivier Tiffet, Noémie Kamlet, Rodrigue Chemaly, Amandine Klipfel, Patrick Pessaux, Cecile Brigand, Serge Rohr, Nicolas Carrère, Chiara Da Re, Frédéric Dumont, Diane Goéré, Dominique Elias, Claude Bertrand, Imperial College London, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de Hautepierre [Strasbourg], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service de chirurgie digestive, CHU Bordeaux [Bordeaux], Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Département de chirurgie digestive, CHU Clermont-Ferrand, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Unité de Chirurgie Colorectale, CHU Grenoble, Environnement Ville Société (EVS), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Unité de Méthodologie en Recherche Clinique, Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Chelsea and Westminster Hospital, Service de Chirurgie Thoracique (NICE - Chirurgie Thoracique), Centre Hospitalier Universitaire de Nice (CHU Nice), West University of Timișoara [Roumanie] (WUT), Service de Chirurgie thoracique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Lab-STICC_UBS_CID_DECIDE, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Mathématiques Informatique et Applications (LAMIA), Université des Antilles et de la Guyane (UAG), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Department of Gastroenterological Surgery, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mutualiste de Montsouris (IMM), Departement medico-chirurgical de pathologie digestive, Chirurgie digestive, Centre Hospitalier Universitaire de Saint-Etienne, Départment de Statistiques Bio-médicales, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de chirurgie digestive [Strasbourg-Hautepierre], Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), R&D, centre de Fresnes, Pfizer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de biostatistiques [CHU Lille], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Hôpital Claude Huriez, Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire Estaing, UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical (UMR PVBMT - INRA), Institut National de la Recherche Agronomique (INRA), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hopital Louis Mourier - AP-HP [Colombes], École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), West University of Timisoara [Roumanie] (UVT), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), ONERA, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ), Site de Recherche Intégrée en Cancérologie ( SIRIC-ONCOLille ), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Chirurgie Générale et Viscérale ( CGV - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Université de Brest ( UBO ), UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical ( UMR PVBMT - INRA ), Institut National de la Recherche Agronomique ( INRA ), Hôpital de la Côte de Nacre, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Ingénierie des Matériaux Polymères - Site Université Claude Bernard Lyon 1 ( IMP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ), Université de Brest ( UBO ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Environnement Ville Société ( EVS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -Université Jean Moulin - Lyon III-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -École Nationale des Travaux Publics de l'État ( ENTPE ) -Ecole Nationale Supérieure des Mines de Saint-Etienne-École nationale supérieure d'architecture de Lyon ( ENSAL ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Centre de recherche en éducation de Nantes ( CREN ), Université de Nantes ( UN ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Chelsea and Westminster Hospital NHS Foundation Trust, Service de Chirurgie Thoracique ( NICE - Chirurgie Thoracique ), CHU Nice, West University of Timisoara [Roumanie], West University of Timisoara, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) ( Lab-STICC ), Université européenne de Bretagne ( UEB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -Université européenne de Bretagne ( UEB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance ( Lab-STICC ), École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -École Nationale d'Ingénieurs de Brest ( ENIB ) -ENSTA Bretagne-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Mathématiques Informatique et Applications ( LAMIA ), Université des Antilles et de la Guyane ( UAG ), Angiogenese et recherche translationnelle ( CART U965 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Institut Mutualiste de Montsouris ( IMM ), CHU Angers, ONERA - The French Aerospace Lab ( Chatillon ), Procédés Alimentaires et Microbiologiques [Dijon] ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté ( UBFC ), and Institut Gustave Roussy ( IGR )

Subjects
Oncology, Subset Analysis, Cancer Research, medicine.medical_specialty, Neoadjuvant treatment, Survival, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Neoadjuvant therapy, [ SDV ] Life Sciences [q-bio], business.industry, Oesophageal cancer, Carcinoma, Phase-III Trial, Cancer, Retrospective cohort study, Chemoradiotherapy, cT2N0M0, medicine.disease, Resection, 3. Good health, Postoperative Mortality, Esophagectomy, 030220 oncology & carcinogenesis, Propensity score matching, Adenocarcinoma, 030211 gastroenterology & hepatology, Surgery, Therapy, business
Abstract

International audience; Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.

Published
2016

46. Is the assessment of submucosal invasion still useful in the management of early rectal cancer? A study of 91 consecutive patients

Author

Najim Chafai, Emmanuel Tiret, Yann Parc, Clotilde Debove, Sylvie Dumont, Magali Svrcek, Jérémie H. Lefevre, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Pathologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Oncology, Male, Local excision, medicine.medical_specialty, Endoscopic Mucosal Resection, Lymphovascular invasion, Colorectal cancer, Gastroenterology, Disease-Free Survival, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Submucosa, medicine, Humans, Neoplasm Invasiveness, Intestinal Mucosa, Pathological, Early Detection of Cancer, Aged, Neoplasm Staging, Transanal Endoscopic Surgery, business.industry, Rectal Neoplasms, Middle Aged, medicine.disease, Total mesorectal excision, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Multivariate Analysis, Tumour budding, 030211 gastroenterology & hepatology, Female, Lymph Nodes, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; AimThe only studies on the prognosis of T1 tumours are old and investigate colic and rectal cancers. Very few studies use Kikuchi's classification (of dividing submucosa into three strata) to evaluate the depth of the submucosal invasion. This study aimed to assess the pathological risk factors for lymph node metastasis (LNM), and the pathological and oncological results of patients with early rectal cancer (ERC, pT1 tumour).MethodBetween 2000 and 2014, 91 consecutive patients undergoing surgery [primary total mesorectal excision (TME) or local excision (LE) alone, or LE followed by TME] for ERC were included.ResultsEighteen patients underwent LE, 22 underwent LE followed by TME and 51 underwent primary total TME. After TME (n = 73), 16 (23%) patients had LNM. The LNM rate was 15% for Sm1 tumours, 14% for Sm2 tumours and 30% for Sm3 tumours. In multivariate analysis, lymphovascular invasion (P = 0.027) and high tumour budding (P = 0.037) were the only independent factors predictive of LNM. The depth of submucosal invasion was not associated with an increased risk of LNM. After a mean follow up of 56 ± 46 months, 5-year overall survival, specific survival and disease-free survival were, respectively, 82%, 93% and 75%. No significant difference of survival was found according to the depth of submucosal invasion or to the surgical management.ConclusionHistological features seem to be stronger risk factors for LNM than depth of submucosal invasion. Considering the LNM rate, TME should be discussed after LE in terms of one of these pathological criteria.

Published
2016

47. Incidence and Risk Factors Related to Symptomatic Venous Thromboembolic Events After Esophagectomy for Cancer

Author

Jean-Michel Fabre, Delphine Lignier, Claude Bertrand, Xaviéra Coueffé, Brice Gayet, Marie Seman, Peggy Jourdan Enfer, Gainant A, Christophe Trésallet, Magalie Cabau, Jacques Jougon, Magalie Lefrançois, Gil Lebreton, Emmanuel Tiret, Nicolas Contival, Styliani Mantziari, Bernard Meunier, Nicolas Demartines, Flora Hec, Alexandre Filipello, Denis Lantuas, Federica Pipitone, Chiara Da Re, Renaud Flamein, François Paye, Denis Collet, Patrick Pessaux, Karine Pautrat, Jean-Marc Bigourdan, Simon Msika, Michel Prudhomme, Johan Gagnière, Jérémie Thereaux, Mehdi Karoui, Patrice Valleur, Diane Goéré, Yann Parc, Mael Chalret du Rieu, Jean-Pierre Bail, Jacques Baulieux, Denis Pezet, Stéphanie Lisunfui, Williams Tessier, Laurent Brunaud, Ion Donici, Marguerite Vanderbeken, Fabien Fredon, N. Chafai, Gilles Poncet, Charlotte Cohen, Jérémie H. Lefevre, Guillaume Luc, Letizia Laface, Serge Rohr, Frédéric Dumont, Jean-Marc Regimbeau, Oussama Baraket, R Frisoni, Serge Cappeliez, Issam El Nakadi, Eric Pappalardo, Marius Nedelcu, Thibault Coste, Marc Pocard, Cécile Brigand, N. Briez, Patrick Lozach, Amandine Klipfel, Gaelle Godiris Petit, Olivier Tiffet, Daniel Pop, Arnaud Alves, Jack Porcheron, Christophe Mariette, Delphine Vaudoyer, Arnaud Pasquer, Frédéric Marchal, Bogdan Stan-Iuga, Thierry Perniceni, Nicolas Carrere, Laurent Villeneuve, Jean-Christophe Vaillant, Caroline Gronnier, Olivier Glehen, B. Malgras, Muriel Mathonnet, Nicolas Venissac, Pierre Balladur, Markus Schäfer, Noémie Kamlet, Olivier Aze, Laurent Bresler, C. Ducerf, Jérôme Mouroux, Dominique Elias, Cyril Cosse, Bogdan Badic, Salim Mezoughi, Jean-Yves Mabrut, Emanuele Felli, Abdennahceur Dhahri, Fabrice Menegaux, Laurent Hannoun, Kathleen Turner, Ahmet Ayav, Mustapha Adam, Rodrigue Chemaly, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne, PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Département de chirurgie digestive, CHU Clermont-Ferrand, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Montreal Heart Institute, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Thoracique (NICE - Chirurgie Thoracique), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU), Babes-Bolyai University [Cluj-Napoca] (UBB), Service de Chirurgie thoracique, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Lab-STICC_UBS_CID_DECIDE, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Mathématiques Informatique et Applications (LAMIA), Université des Antilles et de la Guyane (UAG), Université des Antilles (Pôle Guadeloupe), Université des Antilles (UA), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Association Pro Pictura Antiqua (APPA-CEPMR), Ville de Soissons, CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Hubert Curien (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mutualiste de Montsouris (IMM), Departement medico-chirurgical de pathologie digestive, Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Strasbourg, Laboratoire brestois de mécanique et des systèmes (LBMS), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne), Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Chercheur indépendant, Hospices Civils de Lyon (HCL), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire Estaing, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical (UMR PVBMT - INRA), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hopital Louis Mourier - AP-HP [Colombes], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), equipe 4, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie générale viscérale et endocrinienne [CHU Pitié-Sapêtrière], Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Chirurgie Générale, Viscérale et Endocrinienne [CHU Pitié-Sapêtrière], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN)-Le Mans Université (UM), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service de Chirurgie Hépatobiliaire et Digestive [Rennes], FREGAT Working Group-FRENCH-AFC, Dhahri, A., Lignier, D., Cossé, C., Regimbeau, J.M., Luc, G., Collet, D., Cabau, M., Jougon, J., Badic, B., Lozach, P., Bail, J.P., Cappeliez, S., El Nakadi, I., Lebreton, G., Alves, A., Flamein, R., Pezet, D., Pipitone, F., Stan-Iuga, B., Coueffé, X., Contival, N., Pappalardo, E., Msika, S., Hec, F., Vanderbeken, M., Tessier, W., Briez, N., Fredon, F., Gainant, A., Mathonnet, M., Bigourdan, J.M., Mezoughi, S., Ducerf, C., Baulieux, J., Mabrut, J.Y., Pasquer, A., Baraket, O., Poncet, G., Adam, M., Vaudoyer, D., Enfer, P.J., Villeneuve, L., Glehen, O., Coste, T., Fabre, J.M., Marchal, F., Frisoni, R., Ayav, A., Brunaud, L., Bresler, L., Cohen, C., Aze, O., Venissac, N., Pop, D., Mouroux, J., Donici, I., Prudhomme, M., Felli, E., Lisunfui, S., Seman, M., Petit, G.G., Karoui, M., Tresallet, C., Ménégaux, F., Vaillant, J.C., Hannoun, L., Malgras, B., Lantuas, D., Pautrat, K., Pocard, M., Valleur, P., Lefevre, J., Chafai, N., Balladur, P., Lefranéois, M., Parc, Y., Paye, F., Tiret, E., Nedelcu, M., Laface, L., Perniceni, T., Gayet, B., Turner, K., Meunier, B., Filipello, A., Porcheron, J., Tiffet, O., Kamlet, N., Chemaly, R., Klipfel, A., Pessaux, P., Brigand, C., Rohr, S., Chalret du Rieu, M., Carrére, N., Da Re, C., Dumont, F., Goéré, D., Elias, D., and Bertrand, C.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, ARDS, medicine.medical_specialty, Esophageal Neoplasms, medicine.drug_class, medicine.medical_treatment, Low molecular weight heparin, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030204 cardiovascular system & hematology, Aged, Aged, 80 and over, Esophageal Neoplasms/surgery, Esophagectomy/adverse effects, Female, Hospital Mortality, Humans, Incidence, Length of Stay, Middle Aged, Postoperative Complications/etiology, Risk Factors, Venous Thromboembolism/epidemiology, Venous Thromboembolism/etiology, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Internal medicine, Medicine, cardiovascular diseases, ComputingMilieux_MISCELLANEOUS, business.industry, Incidence (epidemiology), Cancer, Venous Thromboembolism, Esophageal cancer, equipment and supplies, medicine.disease, 3. Good health, Pulmonary embolism, Surgery, Esophagectomy, Venous thrombosis, 030220 oncology & carcinogenesis, Cardiology and Cardiovascular Medicine, business
Abstract

Background Major oncologic surgery is associated with a high incidence of venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). However, the incidence and risk factors for symptomatic VTE during curative treatment for patients with esophageal cancer are poorly documented. Methods Data were collected from 30 European centers from 2000 to 2010. The incidence of in-hospital VTE was assessed in 2,944 patients with esophageal cancer having surgery with curative intent, and 50 clinically relevant parameters were assessed as potential risk factors for VTE. Patients received low molecular weight heparin prophylaxis during hospital stay and for 4 weeks after surgery. Results Eighty-four patients (2.9%) developed a symptomatic VTE; all of them had a DVT and 44 were also diagnosed with a PE. In the VTE group there were 19 postoperative deaths recorded, 5 of which (26.3%) were directly caused by PE at postoperative days 7, 10, 21, 45, and 48 despite VTE prophylaxis. In-hospital postoperative mortality was significantly higher in VTE patients (23% versus 7%, p 0.001) and mean hospital stay was also longer in this group (33 ± 24 versus 25 ± 21 days, p 0.001). Multivariable analysis showed that high American Society of Anesthesiologists (ASA) class ( p = 0.008), pneumopathy ( p = 0.002), or an acute respiratory distress syndrome (ARDS) ( p = 0.015) were significantly associated with VTE. Conclusions Patients with ASA class III or IV and those who present a postoperative pneumopathy or ARDS seem to be at higher risk for VTE. Thus, current VTE screening and thromboprophylaxis for these patients might be inadequate and needs further investigation.

Published
2016

48. Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

Author

Rachel Midgley, Florent Soubrier, Abdelhamid Boumertit, Bruce Winney, Jérémie H. Lefevre, Walter F. Bodmer, Yann Parc, Susan Tonks, Chrystelle Colas, David J. Kerr, Elaine C. Johnstone, Carolina Bonilla, Tammy Day, and Katarzyna Hutnik

Subjects
Adenoma, Adult, medicine.medical_specialty, Colorectal cancer, Adenomatous polyposis coli, Gastroenterology, Article, Gene Frequency, Internal medicine, Genetic variation, Odds Ratio, Genetics, Humans, Medicine, Computer Simulation, Genetic Predisposition to Disease, Age of Onset, Allele frequency, beta Catenin, Genetics (clinical), Adaptor Proteins, Signal Transducing, BRCA2 Protein, biology, business.industry, Case-control study, Genetic Variation, Nuclear Proteins, Odds ratio, Middle Aged, medicine.disease, United Kingdom, Minor allele frequency, DNA Repair Enzymes, Exodeoxyribonucleases, Adenomatous Polyposis Coli, Case-Control Studies, biology.protein, France, Age of onset, Colorectal Neoplasms, MutL Protein Homolog 1, business
Abstract

Some 15–20% of multiple adenomatous polyposis have no genetic explanation and 20–30% of colorectal cancer (CRC) cases are thought to be due to inherited multifactorial causes. Accumulation of deleterious effects of low-frequency dominant and independently acting variants may be a partial explanation for such patients. The aim of this study was to type a selection of rare and low-frequency variants (

Published
2012

49. Unexplained polyposis: a challenge for geneticists, pathologists and gastroenterologists

Author

Lahely Y, Mélanie Eyries, Magali Svrcek, Jean-François Fléjou, Florent Soubrier, Jérémie H. Lefevre, Yann Parc, Florence Coulet, Chrystelle Colas, and C Mongin

Subjects
Adult, Male, Gastrointestinal Diseases, Colorectal cancer, Adenomatous Polyposis Coli Protein, DNA Mutational Analysis, Colorectal polyposis, Nucleic Acid Denaturation, DNA Glycosylases, Familial adenomatous polyposis, Frameshift mutation, Cohort Studies, Germline mutation, MUTYH, Genetics, medicine, Humans, Point Mutation, Genetic Testing, Frameshift Mutation, Wnt Signaling Pathway, Bone Morphogenetic Protein Receptors, Type I, Germ-Line Mutation, Genetics (clinical), Aged, Smad4 Protein, Genetic testing, medicine.diagnostic_test, Mosaicism, business.industry, Membrane Proteins, Middle Aged, medicine.disease, BMPR1A, Adenomatous Polyposis Coli, Cancer research, Intercellular Signaling Peptides and Proteins, business
Abstract

Two main colorectal polyposis syndromes have been described, familial adenomatous polyposis and MUTYH-associated polyposis syndromes. Some polyposis remains unexplained: 20% of adenomatous polyposis and serrated polyposis. The aim of this study was to evaluate in a cohort of patients with unexplained polyposis whether a genetic defect could be detected. Individuals presenting polyposis with more than 40 adenomas or more than 20 serrated polyps (hyperplastic, sessile serrated and mixed), without causative mutation identified, were included. Complementary explorations on APC or MUTYH were performed: search for APC mosaicism, splicing-affecting mutations, large genomic rearrangement of MUTYH. Four genes of Wnt pathway (AXIN2, PPP2R1B, WIF1, SFRP1) and two genes of transforming growth factor-β (TGF-β) pathway (SMAD4, BMPR1A) were screened for germline mutation. Twenty-five patients had an unexplained adenomatous polyposis (familial or sporadic). Five pathogenic mutations were found: four in APC gene (with one case of mosaicism) and one in BMPR1A gene. The exploration of APC mosaicism was better performed from adenoma DNA with high-resolution melting. The screening of the candidate genes did not find any causative mutation. Thirteen individuals had an unexplained serrated polyposis and a frameshift on SMAD4 gene was identified. All mutations were identified in familial cases of polyposis. After new pathological examination, both BMPR1A and SMAD4 cases were found to be associated with a juvenile polyposis while the polyposis was initially described as adenomatous or undetermined. In 17% (6/38) of the patients the causative mutation of the polyposis was identified. Genetic causes were heterogeneous. Sporadic polyposis patients must be considered as potential APC mosaicism. The histological classification of polyposis is strongly important in direct genetic exploration.

Published
2011

50. Clinical Challenges and Images in GI

Author

Najat Mourra, Yann Parc, and Maïté Lewin

Subjects
medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Gastroenterology, MEDLINE, Esophagus surgery, Text mining, X ray computed, Esophagectomy, Gene duplication, Medicine, Radiology, business
Published
2008

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