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1.
Ann Surg Open ; 5(1): e397, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38883962

RÉSUMÉ

Objective: Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications. Methods: A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208. Results: Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56-44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2-59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0-59.5) and 19.8% to 62.9% (IQR, 37.3-46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively. Conclusions: This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.

2.
Surg Endosc ; 38(2): 488-498, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38148401

RÉSUMÉ

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.


Sujet(s)
Tumeurs de l'estomac , Humains , Méthode Delphi , Consensus , Tumeurs de l'estomac/chirurgie , Reproductibilité des résultats , Lymphadénectomie , Anastomose chirurgicale , Gastrectomie
3.
Inflamm Bowel Dis ; 2023 Oct 20.
Article de Anglais | MEDLINE | ID: mdl-37862577

RÉSUMÉ

Muscular health, encompassing sarcopenia and myosteatosis, has a pivotal role in optimizing surgical outcomes in patients with Crohn's disease. A comprehensive approach is advocated for improving patient well-being after surgery.

4.
Updates Surg ; 75(8): 2279-2290, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37805973

RÉSUMÉ

The best nonoperative or operative anal fissure (AF) treatment is not yet established, and several options have been proposed. Aim is to report the surgeons' practice for the AF treatment. Thirty-four multiple-choice questions were developed. Seven questions were about to participants' demographics and, 27 questions about their clinical practice. Based on the specialty (general surgeon and colorectal surgeon), obtained data were divided and compared between two groups. Five-hundred surgeons were included (321 general and 179 colorectal surgeons). For both groups, duration of symptoms for at least 6 weeks is the most important factor for AF diagnosis (30.6%). Type of AF (acute vs chronic) is the most important factor which guide the therapeutic plan (44.4%). The first treatment of choice for acute AF is ointment application for both groups (59.6%). For the treatment of chronic AF, this data is confirmed by colorectal surgeons (57%), but not by the general surgeons who prefer the lateral internal sphincterotomy (LIS) (31.8%) (p = 0.0001). Botulin toxin injection is most performed by colorectal surgeons (58.7%) in comparison to general surgeons (20.9%) (p = 0.0001). Anal flap is mostly performed by colorectal surgeons (37.4%) in comparison to general surgeons (28.3%) (p = 0.0001). Fissurectomy alone is statistically significantly most performed by general surgeons in comparison to colorectal surgeons (57.9% and 43.6%, respectively) (p = 0.0020). This analysis provides useful information about the clinical practice for the management of a debated topic such as AF treatment. Shared guidelines and consensus especially focused on operative management are required to standardize the treatment and to improve postoperative results.


Sujet(s)
Toxines botuliniques de type A , Tumeurs colorectales , Fissure anale , Agents neuromusculaires , Chirurgiens , Humains , Fissure anale/chirurgie , Fissure anale/traitement médicamenteux , Agents neuromusculaires/usage thérapeutique , Maladie chronique , Canal anal/chirurgie , Tumeurs colorectales/traitement médicamenteux , Résultat thérapeutique
5.
Updates Surg ; 75(6): 1617-1623, 2023 Sep.
Article de Anglais | MEDLINE | ID: mdl-37368229

RÉSUMÉ

Several objective severity measurement questionnaires of the fecal incontinence (FI), are available to describe type, frequency and degree of FI, and their impact on quality of life, aiming to establish baseline scores measure response to treatment over time and allow comparison among patients treated using different strategies. Presently, despite their widespread use in clinical practice, none of these questionnaire have been validated in the Italian language. The aim is to test the translated Italian version of the Vaizey and Wexner and Fecal Incontinence Severity Index (FISI) questionnaires assessing their reliability and validity among Italian-speaking patients. Two researchers proficient in spoken English and Italian translated both questionnaires in the Italian language. They independently translated the two questionnaires from English and then they met to produce a single version of the two questionnaires, to solve any possible discrepancy. A forward-backward translation was then obtained by a professional bilingual translator, so as to define the final version of the questionnaires. The questionnaires were independently administered twice to 100 Italian-speaking patients by two different and independent raters. Cronbach's α of the first and second Vaizey and Wexner questionnaire was 0.755 and 0.727, respectively. While Cronbach's α of the first and second FISI questionnaire was 0.810 and 0.806, respectively. Spearman correlation and inter-rater reliability were 0.937 and 0.913 for Vaizey and Wexner questionnaire, respectively, and 0.915 and 0.871 for FISI questionnaire, respectively. Italian version of the Vaizey and Wexner and FISI questionnaires proved good consistency, reliability, reproducibility, showing good psychometric properties.


Sujet(s)
Incontinence anale , Qualité de vie , Humains , Reproductibilité des résultats , Études prospectives , Incontinence anale/diagnostic , Indice de gravité de la maladie , Langage , Enquêtes et questionnaires , Italie
6.
Updates Surg ; 75(3): 627-634, 2023 Apr.
Article de Anglais | MEDLINE | ID: mdl-36899291

RÉSUMÉ

Perirectal hematoma (PH) is one of the most feared complications of stapling procedures. Literature reviews have reported only a few works on PH, most of them describing isolated treatment approaches and severe outcomes. The aim of this study was to analyze a homogenous case series of PH and to define a treatment algorithm for huge postoperative PHs. A retrospective analysis of a prospective database of three high-volume proctology units was performed between 2008 and 2018, and all PH cases were analyzed. In all, 3058 patients underwent stapling procedures for hemorrhoidal disease or obstructed defecation syndrome with internal prolapse. Among these, 14 (0.46%) large PH cases were reported, and 12 of these hematomas were stable and treated conservatively (antibiotics and CT/laboratory test monitoring); most of them were resolved with spontaneous drainage. Two patients with progressive PH (signs of active bleeding and peritonism) were submitted to CT and arteriography to evaluate the source of bleeding, which was subsequently closed by embolization. This approach helped ensure that no patients with PH were referred for major abdominal surgery. Most PH cases are stable and treatable with a conservative approach, evolving with self-drainage. Progressive hematomas are rare and should undergo angiography with embolization to minimize the possibility of major surgery and severe complications.


Sujet(s)
Hémorroïdes , Humains , Hémorroïdes/chirurgie , Défécation , Études rétrospectives , Agrafage chirurgical/effets indésirables , Agrafage chirurgical/méthodes , Prolapsus , Hématome/étiologie , Hématome/thérapie , Résultat thérapeutique , Complications postopératoires/thérapie , Complications postopératoires/chirurgie
7.
Inflamm Bowel Dis ; 29(4): 539-547, 2023 04 03.
Article de Anglais | MEDLINE | ID: mdl-35640113

RÉSUMÉ

BACKGROUND: Two-thirds of Crohn's disease (CD) patients require surgery during their disease course. However, surgery is not curative, and endoscopic recurrence is observed in up to 90% of cases. Our aim was to investigate the impact of postoperative biological therapy on the incidence of endoscopic recurrence and long-term outcomes in CD patients. METHODS: This retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Milan, Italy) between 2014 and 2021. All consecutive CD patients who underwent surgery and colonoscopy at 6-12 months postoperatively were eligible for inclusion. RESULTS: A total of 141 patients were included (42.6% female, mean age 44 years). Median follow-up was 28 months. About one-third of patients were treated with biologics at baseline colonoscopy. A higher rate of endoscopic recurrence was detected in patients without biologic therapy at the time of colonoscopy compared with those treated (80.8% vs 45.2%, P < .0001). Hospitalization and surgery occurred more in untreated patients than in subjects undergoing biological therapy (12.1% vs 0.0%, P = .01). The Kaplan-Meier curves showed that the no treatment group at baseline had a >23.3% 5-year rate of hospitalization and surgery (log-rank P = .0221) and a >49.7% 5-year rate of medical therapy escalation (log-rank P = .0013) compared with the treatment arm. In the logistic regression model, absence of biologic therapy was independently associated with the risk of endoscopic disease recurrence (odds ratio, 0.22; 95% CI, 0.1-0.51; P = .0004). CONCLUSION: Operated CD patients treated early with biologics experience decreased rates of endoscopic recurrence and improved long-term outcomes.


Sujet(s)
Produits biologiques , Maladie de Crohn , Humains , Femelle , Adulte , Mâle , Maladie de Crohn/traitement médicamenteux , Maladie de Crohn/chirurgie , Études rétrospectives , Coloscopie , Biothérapie , Produits biologiques/usage thérapeutique , Récidive , Résultat thérapeutique
8.
Colorectal Dis ; 25(4): 647-659, 2023 04.
Article de Anglais | MEDLINE | ID: mdl-36527323

RÉSUMÉ

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.


Sujet(s)
Tumeurs du rectum , Rectum , Humains , Rectum/chirurgie , Rectum/anatomopathologie , Iléostomie/effets indésirables , Tumeurs du rectum/anatomopathologie , Désunion anastomotique/étiologie , Anastomose chirurgicale/effets indésirables , Études rétrospectives
9.
Surgery ; 172(6S): S38-S45, 2022 12.
Article de Anglais | MEDLINE | ID: mdl-36427929

RÉSUMÉ

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.


Sujet(s)
Chirurgie colorectale , Procédures de chirurgie digestive , Humains , Vert indocyanine , Imagerie optique , Biopsie de noeud lymphatique sentinelle
12.
Updates Surg ; 74(3): 1017-1025, 2022 Jun.
Article de Anglais | MEDLINE | ID: mdl-35322388

RÉSUMÉ

During the corona virus disease 2019 (COVID-19) pandemic, most of the surgical procedures were performed for emergencies or oncologic reasons to the detriment of the remaining elective procedures for benign conditions. Ileostomy or colostomy creation are sequelae of oncologic or emergency colorectal surgery, but their closure does not fall within the definition of oncologic or emergency surgery. The aim of this retrospective multicentre observational study is to report the impact of COVID-19 pandemic on the ostomy closure rate in Italy. Data regarding ileostomy and colostomy creation and closure from 24 Italian centres, during the study period (March 2020-February 2021) and during the control period (March 2019-February 2020) were collected. Three hospitals (12.5%) were COVID free. The number of colostomies and ileostomies created and closed in the same period was lower ( -18.8% and -30%, respectively) in the study period in comparison to the control period (p = 0.1915 and p = 0.0001, respectively), such as the ostomies closed in the analysed periods but created before (colostomy -36.2% and ileostomy -7.4%, p = 0.2211 and p = 0.1319, respectively). Overall, a 19.5% reduction in ostomies closed occurred in the study period. Based on the present study, a reduction in ostomy closure rate occurred in Italy between March 2020 and February 2021. During the pandemic, the need to change the clinical practice probably prolonged deterioration of quality of life in patients with ostomies, increasing number of stomas that will never be closed, and related management costs, even if these issues have not been investigated in this study.


Sujet(s)
COVID-19 , Ostomie , Colostomie/méthodes , Humains , Ostomie/méthodes , Pandémies , Qualité de vie
14.
Inflamm Bowel Dis ; 28(6): 971-976, 2022 06 03.
Article de Anglais | MEDLINE | ID: mdl-35032171

RÉSUMÉ

The JAK/STAT inhibitor tofacitinib, recently approved for the treatment of ulcerative colitis, is found to modulate the intestinal endothelial barrier functions in directing the leukocyte adhesion and transmigration in ulcerative colitis patients displaying high levels of endothelial STAT3/STAT6 phosphorylation.


Sujet(s)
Rectocolite hémorragique , Rectocolite hémorragique/traitement médicamenteux , Humains , Leucocytes , Pipéridines/pharmacologie , Pyrimidines/pharmacologie , Pyrimidines/usage thérapeutique
15.
Langenbecks Arch Surg ; 407(1): 421-428, 2022 Feb.
Article de Anglais | MEDLINE | ID: mdl-34269879

RÉSUMÉ

INTRODUCTION: This How-I-Do-It article presents a modified Deloyers procedure by mean of the case of a 67-year-old female with adenocarcinoma extending for a long segment and involving the splenic flexure and proximal descending colon who underwent a laparoscopic left extended hemicolectomy (LELC) with derotation of the right colon and primary colorectal anastomosis. BACKGROUND: While laparoscopic extended right colectomy is a well-established procedure, LELC is rarely used (mainly for distal transverse or proximal descending colon carcinomas extending to the area of the splenic flexure). LELC presents several technical challenges which are demonstrated in this How-I-Do-It article. TECHNIQUE AND METHODS: Firstly, the steps needed to mobilize the left colon and procure a safe approach to the splenic flexure are described, especially when a tumor is closely related to it. This is achieved by mobilization and resection of the descending colon, while maintaining a complete mesocolic excision to the level of the duodenojejunal ligament for the inferior mesenteric vein and flush to the aorta for the inferior mesenteric artery. Subsequently, we depict the adjuvant steps required to enable a primary anastomosis by trying to mobilize the transverse colon and release as much of the mesocolic attachments at the splenic flexure area. Finally, we present the rare instance when a laparoscopic derotation of the ascending colon is required to provide a tension-free anastomosis. The resection is completed by delivery of the fully derotated ascending colon and hepatic flexure through a suprapubic mini-Pfannenstiel incision. The primary colorectal anastomosis is subsequently fashioned in a tension-free way and provides for a quick postoperative recovery of the patient. RESULTS: This modified Deloyers procedure preserves the middle colic since the fully mobilized mesocolon allows for a tension-free anastomosis while maintaining better blood supply to the mobilized stump. Also, by eliminating the need for a mesenteric window and the transposition of the caecum, we allow the small bowel to rest over the anastomosis and the mobilized transverse colon and reduce the possibility of an internal herniation of the small bowel into the mesentery. CONCLUSIONS: Laparoscopic derotation of the right colon and a partial, modified Deloyers procedure preserving the middle colic vessels are feasible techniques in experienced hands to provide primary anastomosis after LELC with improved functional outcome. Nevertheless, it is important to consider anatomical aspects of the left hemicolectomy along with oncological considerations, to provide both a safe oncological resection along with good postoperative bowel function.


Sujet(s)
Adénocarcinome , Colique , Côlon transverse , Tumeurs du côlon , Laparoscopie , Adénocarcinome/chirurgie , Sujet âgé , Anastomose chirurgicale , Colectomie , Côlon transverse/chirurgie , Tumeurs du côlon/chirurgie , Femelle , Humains
16.
Infect Agent Cancer ; 16(1): 62, 2021 Oct 30.
Article de Anglais | MEDLINE | ID: mdl-34717691

RÉSUMÉ

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.

18.
Mol Clin Oncol ; 15(1): 136, 2021 Jul.
Article de Anglais | MEDLINE | ID: mdl-34055351

RÉSUMÉ

The use of biliary stents has become a common and usually safe procedure. However, the migration of biliary stents is an uncommon but well-recognized event after endoscopic retrograde cholangiopancreatography. The migration of plastic stents usually does not result in complications and are spontaneously eliminated from the gastro-intestinal tract. Additionally, <1% of migrated stents result in intestinal perforation, which typically occurs at the duodenum. Chemotherapeutic agents may cause gastrointestinal toxicity and hematologic toxicity predisposing to neutropenic enterocolitis. The current study reports a patient with an unprecedented case of biliary stent migration resulting in appendiceal gangrene and perforation in a neutropenic patient under chemotherapy for metastatic small cell lung cancer.

19.
Updates Surg ; 73(2): 503-512, 2021 Apr.
Article de Anglais | MEDLINE | ID: mdl-33534125

RÉSUMÉ

Neuro-anatomy of the perineum has gained renewed attention due to its significance in the transanal procedures for rectal cancer (eg TaTME). Surgeons embarking on this technique must have sophisticated knowledge and a precise anatomical understanding of the perineum before proceeding with this reversed rectal approach. We report anatomical observations deriving from a relevant experience in the colorectal surgery field. The collective multicenter experience of the present study is clinically relevant and based on the rectal and transanal resections performed in colorectal centers of excellence from Greece, UK, and Italy over the last 10 years (2011-2020). From the original anatomical and intraoperative observations derived from collective cases operated by this multicenter group of colorectal surgical centers in three European countries, data were retrieved and analyzed in collaboration with specialist researchers of human anatomy and interpreted for their clinical significance and potential use for preoperative planning and intraoperative guidance during TaTME. This descriptive article demonstrates in detail the neurogenic pathways encountered in the perineum and pelvic cavity during transanal procedures. Specific anatomical and topographic implications are also included serving as a guide for colorectal surgeons to perform a nerve-sparing procedure. transanal approach for rectal excision offers new insights into the complex pelvic and perineal neuroanatomy while the procedure itself remains a challenge for surgeons. Preoperative anatomical planning and 3D reconstruction may help in anticipating technical difficulties, resulting in more precise surgical dissections and decreased postoperative complications.


Sujet(s)
Laparoscopie , Tumeurs du rectum , Chirurgie endoscopique transanale , Humains , Neuroanatomie , Pelvis/chirurgie , Complications postopératoires , Tumeurs du rectum/chirurgie , Rectum/chirurgie
20.
Cell Mol Gastroenterol Hepatol ; 11(2): 639-658, 2021.
Article de Anglais | MEDLINE | ID: mdl-33091622

RÉSUMÉ

BACKGROUND & AIMS: The fragile X mental retardation protein (FMRP) affects multiple steps of the mRNA metabolism during brain development and in different neoplastic processes. However, the contribution of FMRP in colon carcinogenesis has not been investigated. METHODS: FMR1 mRNA transcript and FMRP protein expression were analyzed in human colon samples derived from patients with sporadic colorectal cancer (CRC) and healthy subjects. We used a well-established mouse model of sporadic CRC induced by azoxymethane to determine the possible role of FMRP in CRC. To address whether FMRP controls cancer cell survival, we analyzed cell death pathway in CRC human epithelial cell lines and in patient-derived colon cancer organoids in presence or absence of a specific FMR1 antisense oligonucleotide or siRNA. RESULTS: We document a significant increase of FMRP in human CRC relative to non-tumor tissues. Next, using an inducible mouse model of CRC, we observed a reduction of colonic tumor incidence and size in the Fmr1 knockout mice. The abrogation of FMRP induced spontaneous cell death in human CRC cell lines activating the necroptotic pathway. Indeed, specific immunoprecipitation experiments on human cell lines and CRC samples indicated that FMRP binds receptor-interacting protein kinase 1 (RIPK1) mRNA, suggesting that FMRP acts as a regulator of necroptosis pathway through the surveillance of RIPK1 mRNA metabolism. Treatment of human CRC cell lines and patient-derived colon cancer organoids with the FMR1 antisense resulted in up-regulation of RIPK1. CONCLUSIONS: Altogether, these data support a role for FMRP  in controlling RIPK1 expression and necroptotic activation in CRC.


Sujet(s)
Tumeurs colorectales/génétique , Protéine du syndrome X fragile/métabolisme , Récidive tumorale locale/épidémiologie , Receptor-Interacting Protein Serine-Threonine Kinases/génétique , Animaux , Oxyde de diméthyl-diazène/administration et posologie , Oxyde de diméthyl-diazène/toxicité , Carcinogenèse/génétique , Études cas-témoins , Techniques de culture cellulaire , Lignée cellulaire tumorale , Côlon/anatomopathologie , Côlon/chirurgie , Tumeurs colorectales/induit chimiquement , Tumeurs colorectales/mortalité , Tumeurs colorectales/chirurgie , Jeux de données comme sujet , Survie sans rechute , Protéine du syndrome X fragile/antagonistes et inhibiteurs , Protéine du syndrome X fragile/génétique , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes tumoraux/génétique , Techniques de knock-down de gènes , Volontaires sains , Humains , Mâle , Souris , Souris knockout , Nécroptose/génétique , Récidive tumorale locale/génétique , Tumeurs expérimentales/induit chimiquement , Tumeurs expérimentales/génétique , Tumeurs expérimentales/anatomopathologie , Organoïdes , Pronostic
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