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1.
Gastrointest Endosc ; 100(4): 703-709.e4, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38462057

RESUMO

BACKGROUND AND AIMS: The modified Rutgeerts score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn's disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, 2 new scores have been proposed. This study assessed the interobserver agreement of the current score (mRS) and the new endoscopic score for ePOR in CD. METHODS: Sixteen Dutch academic and nonacademic inflammatory bowel disease specialists assessed endoscopic videos (n = 71) of postoperative CD patients (n = 66) retrieved from 9 Dutch centers. Each video was assessed for degree of inflammation by 4 gastroenterologists using the mRS and the new proposed endoscopic score: the REMIND score (separate score of anastomosis and neoterminal ileum) and the updated Rutgeerts score (assessment of lesions at the anastomotic line, ileal inlet, ileal body, and neoterminal ileum). In addition, lesions at the ileal body, ileal inlet, neoterminal ileum, and colonic and/or ileal blind loop were separately assessed. Interobserver agreement was assessed by using Fleiss' weighted kappa. RESULTS: Fleiss' weighted kappa for the mRS was .67 (95% confidence interval [CI], .59-.74). The weighted kappa for the REMIND score was .73 (95% CI, .65-.80) for lesions in the neoterminal ileum and .46 (95% CI, .35-.58) for anastomotic lesions. The weighted kappa for the updated Rutgeerts score was .69 (95% CI, .62-.77). The weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, and colonic and ileal blind loop was .61 (95% CI, .49-.73), .63 (95% CI, .54-.72), .61 (95% CI, .49-.74), .83 (95% CI, .62-1.00) and .68 (95% CI, .46-.89), respectively. CONCLUSIONS: The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for the updated Rutgeerts score. According to the REMIND score, the interobserver agreement was substantial for lesions in the neoterminal ileum, although only moderate for anastomotic lesions. Because therapeutic decisions in clinical practice are based on these assessments, and these scores are used as outcome measure in clinical studies, further improvement of the interobserver agreement is essential.


Assuntos
Anastomose Cirúrgica , Doença de Crohn , Íleo , Variações Dependentes do Observador , Recidiva , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/patologia , Feminino , Íleo/cirurgia , Íleo/patologia , Masculino , Adulto , Colo/patologia , Colo/cirurgia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Colonoscopia/métodos , Adulto Jovem
2.
CA Cancer J Clin ; 67(5): 411-431, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28683174

RESUMO

Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.


Assuntos
Hepatite C Crônica , Neoplasias Hepáticas/virologia , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/terapia
3.
Scand J Gastroenterol ; 59(5): 553-560, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353236

RESUMO

BACKGROUND: Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. METHODS: We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. RESULTS: From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. CONCLUSION: IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation.What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity.How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade a Drogas , Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Infliximab , Humanos , Infliximab/uso terapêutico , Infliximab/administração & dosagem , Infliximab/imunologia , Infliximab/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/etiologia , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/imunologia , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Resultado do Tratamento , Adulto Jovem
4.
Gut ; 72(4): 699-709, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35803702

RESUMO

OBJECTIVE: T cells are major effectors of the antitumoural immune response. Their activation by tumour-associated antigens can unleash their proliferation and cytotoxic functions, leading to tumour cell elimination. However, tumour-related immunosuppressive mechanisms including the overexpression of immune checkpoints like programmed cell death protein-1 (PD-1), are also engaged, promoting immune escape. Current immunotherapies targeting these pathways have demonstrated weak efficacy in colorectal cancer (CRC). It is thus crucial to find new targets for immunotherapy in this cancer type. DESIGN: In a prospective cohort of patients with CRC, we investigated the phenotype of tumour-related and non-tumour related intestinal T cells (n=44), particularly the adenosinergic pathway, correlating with clinical phenotype. An autologous coculture model was developed between patient-derived primary tumour spheroids and their autologous tumour-associated lymphocytes. We used this relevant model to assess the effects of CD39 blockade on the antitumour T cell response. RESULTS: We show the increased expression of CD39, and its co-expression with PD-1, on tumour infiltrating T cells compared with mucosal lymphocytes. CD39 expression was higher in the right colon and early-stage tumours, thus defining a subset of patients potentially responsive to CD39 blockade. Finally, we demonstrate in autologous conditions that CD39 blockade triggers T cell infiltration and tumour spheroid destruction in cocultures. CONCLUSION: In CRC, CD39 is strongly expressed on tumour infiltrating lymphocytes and its inhibition represents a promising therapeutic strategy for treating patients.


Assuntos
Neoplasias Colorretais , Linfócitos T , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , Intestinos/patologia , Neoplasias Colorretais/patologia
5.
Gut ; 72(1): 39-48, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35361684

RESUMO

OBJECTIVE: We used the postoperative recurrence model to better understand the role of adherent and invasive Escherichia coli (AIEC) bacteria in Crohn's disease (CD), taking advantage of a well-characterised postoperative cohort. DESIGN: From a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts' index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders. RESULTS: AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus. CONCLUSION: Based on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD. TRIAL REGISTRATION NUMBER: NCT03458195.


Assuntos
Doença de Crohn , Infecções por Escherichia coli , Humanos , Aderência Bacteriana , Colonoscopia , Doença de Crohn/patologia , Escherichia coli , Infecções por Escherichia coli/epidemiologia , Íleo/microbiologia , Estudos Prospectivos , Recidiva
6.
Surg Endosc ; 36(8): 5660-5668, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35790591

RESUMO

BACKGROUND: Predictors of the efficacy of endoscopic dilation for caustic esophageal stricture have been poorly studied. METHODS: All patients undergoing an endoscopic dilation for an esophageal caustic stricture between 1990 and 2015 in a French national reference center were included. Success of dilation was defined by self-food autonomy without the need for reconstructive esophageal surgery. RESULTS: During the study period, 894 patients were admitted after caustic ingestion. Among them, 101 patients developed esophageal stricture and 92 patients were eligible for analysis (missing data in 8 cases, 1 patient died before endoscopic dilation). In this cohort (median age 42 years, women 53%, strong alkali 74%, suicide attempt 77%, hydrostatic balloon use 93%), the overall success rate of dilation was 57% with a median number of 3 dilation sessions (274 sessions, range 1-17). Factors predicting the success of the procedure were: non-inflammatory stricture or non-inflammatory intercalated mucosa between stricture (88% vs 47%, p = 0.001), a single stricture versus 2 or more strictures (69% vs 47% vs 33%, respectively, p = 0.04), a stricture of less than 5 cm (70% vs 27%, p < 0.001) and the existence of mild/ moderately tight or very tight stricture (70% vs 21% of success, p < 0.001). Perforation rate was 6.5% (18/274) requiring emergency surgery in 2 cases. CONCLUSION: Several characteristics of caustic esophageal strictures are significantly associated with the success rate of endoscopic dilation. Our data may be useful for customizing treatment strategies in patients with a caustic stricture.


Assuntos
Cáusticos , Estenose Esofágica , Adulto , Cáusticos/toxicidade , Constrição Patológica , Dilatação/métodos , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/cirurgia , Feminino , Humanos , Estudos Retrospectivos , Resultado do Tratamento
7.
Gut ; 69(11): 1939-1951, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32111634

RESUMO

OBJECTIVE: Reduced Paneth cell (PC) numbers are observed in inflammatory bowel diseases and impaired PC function contributes to the ileal pathogenesis of Crohn's disease (CD). PCs reside in proximity to Lgr5+ intestinal stem cells (ISC) and mitochondria are critical for ISC-renewal and differentiation. Here, we characterise ISC and PC appearance under inflammatory conditions and describe the role of mitochondrial function for ISC niche-maintenance. DESIGN: Ileal tissue samples from patients with CD, mouse models for mitochondrial dysfunction (Hsp60Δ/ΔISC) and CD-like ileitis (TNFΔARE), and intestinal organoids were used to characterise PCs and ISCs in relation to mitochondrial function. RESULTS: In patients with CD and TNFΔARE mice, inflammation correlated with reduced numbers of Lysozyme-positive granules in PCs and decreased Lgr5 expression in crypt regions. Disease-associated changes in PC and ISC appearance persisted in non-inflamed tissue regions of patients with CD and predicted the risk of disease recurrence after surgical resection. ISC-specific deletion of Hsp60 and inhibition of mitochondrial respiration linked mitochondrial function to the aberrant PC phenotype. Consistent with reduced stemness in vivo, crypts from inflamed TNFΔARE mice fail to grow into organoids ex vivo. Dichloroacetate-mediated inhibition of glycolysis, forcing cells to shift to mitochondrial respiration, improved ISC niche function and rescued the ability of TNFΔARE mice-derived crypts to form organoids. CONCLUSION: We provide evidence that inflammation-associated mitochondrial dysfunction in the intestinal epithelium triggers a metabolic imbalance, causing reduced stemness and acquisition of a dysfunctional PC phenotype. Blocking glycolysis might be a novel drug target to antagonise PC dysfunction in the pathogenesis of CD.


Assuntos
Doença de Crohn/etiologia , Doença de Crohn/patologia , Mitocôndrias/fisiologia , Celulas de Paneth/patologia , Células-Tronco/citologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Humanos , Camundongos , Recidiva , Nicho de Células-Tronco
8.
Clin Gastroenterol Hepatol ; 18(1): 141-149.e2, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042575

RESUMO

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


Assuntos
Doença de Crohn/patologia , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Íleo , Margens de Excisão , Adulto , Anastomose Cirúrgica/efeitos adversos , Colectomia/efeitos adversos , Colectomia/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Humanos , Íleo/patologia , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva
9.
Am J Gastroenterol ; 115(7): 1084-1093, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618659

RESUMO

INTRODUCTION: Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. METHODS: The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. RESULTS: Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). DISCUSSION: A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.


Assuntos
Doença de Crohn/cirurgia , Doenças do Íleo/cirurgia , Complicações Pós-Operatórias/diagnóstico , Adulto , Anastomose Cirúrgica , Colonoscopia , Progressão da Doença , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva
11.
Am J Gastroenterol ; 116(1): 218, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33009056
12.
N Engl J Med ; 377(6): 596, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28792870

Assuntos
Asma , Pulmão , Humanos
14.
Ther Adv Med Oncol ; 16: 17588359241280541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314916

RESUMO

Malignant PEComas are an extremely rare subtype of soft tissue sarcomas. Here, we report the case of a man presenting with a perirectal PEComa and liver metastasis. Since the tumor harbored a tumor mutational burden of 23/Mb and a programmed death-ligand 1 tumor positivity score of 50%, the patient was treated with pembrolizumab as a second line of systemic therapy, in combination with everolimus. This combined therapy led to a near-complete response of the primary tumor and a partial response of the metastasis. Radioembolization of the liver metastasis was performed due to isolated liver progression, and the pelvic tumor was treated by radiotherapy because of pelvic symptoms. The disease is still stable after 13 months of pembrolizumab plus everolimus and multimodal treatment. This case shows that malignant PEComas can display molecular features associated with sensitivity to checkpoint inhibitors. The use of checkpoint inhibitors may be a relevant therapeutic strategy in these patients. It is also the first report on selective internal radiation therapy in PEComas.


A case of a patient with metastatic PEComa of the rectum, a very rare tumor type, treated by immunotherapy in combination with local treatments This article reports the case of a patient presenting with a very rare tumor type called "PEComa". The tumor originated from the rectum and had disseminated to the liver. Since this tumor is very rare, there is a lack of knowledge on which treatments to use, and every case reporting the use of new treatments in PEComas is helpful. Here, the tumor displayed molecular alterations that suggested that it would respond to immunotherapy, such as a high number of mutations. Therefore, the patient was treated with an immunotherapy called pembrolizumab, in combination with another medication (everolimus). The rectal tumor nearly disappeared under treatment, and the liver metastasis decreased in size. The patient had radiotherapy of the rectum because of rectal bleeding. For the liver metastasis we used another technique called radioembolization, that consists in delivering radioactive compounds directly in the metastasis through the bloodstream. Now, he has received immunotherapy for 13 months and the disease is still under control. This case shows that immunotherapy can be a good treatment option in PEComas. It is also the first time that a medical team reports the using radioembolization to treat a PEComa.

15.
Aliment Pharmacol Ther ; 60(3): 310-326, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38887827

RESUMO

BACKGROUND: Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. AIMS: To assess the current evidence on patient-related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re-)resection. METHODS: Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient-related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle-Ottawa Scale for observational cohort studies and case-control studies. RESULTS: In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case-control studies, one cross-sectional study and one individual participant data meta-analysis) including 6006 patients (median sample size 87 patients [interquartile range 46-170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post-surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient-related, microbial, surgical and histopathological factors. CONCLUSION: Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence-based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required.


Assuntos
Doença de Crohn , Recidiva , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/patologia , Fatores de Risco
16.
J Crohns Colitis ; 18(6): 943-957, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38112601

RESUMO

BACKGROUND: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries. METHODS: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded. RESULTS: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications. CONCLUSIONS: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.


Assuntos
Doença de Crohn , Recidiva , Doença de Crohn/cirurgia , Humanos , Íleo/cirurgia , Íleo/patologia
17.
J Crohns Colitis ; 17(10): 1557-1568, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37070326

RESUMO

Postoperative recurrence [POR] after an ileocolonic resection with ileocolonic anastomosis is frequently encountered in patients with Crohn's disease. The 8th Scientific Workshop of ECCO reviewed the available evidence on the pathophysiology and risk factors for POR. In this paper, we discuss published data on the role of the microbiome, the mesentery, the immune system and the genetic background. In addition to investigating the causative mechanisms of POR, identification of risk factors is essential to tailor preventive strategies. Potential clinical, surgical and histological risk factors are presented along with their limitations. Emphasis is placed on unanswered research questions, guiding prevention of POR based on individual patient profiles.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/patologia , Colo/cirurgia , Colo/patologia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Íleo/cirurgia , Íleo/patologia , Estudos Retrospectivos , Fatores de Risco , Recidiva
18.
J Crohns Colitis ; 17(9): 1373-1386, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37070339

RESUMO

Despite the introduction of potent biologic therapies, many patients with Crohn's disease [CD] still require an ileocolonic resection [ICR] during the course of their disease. Furthermore, the need of redo ICR has not decreased over the past few decades, highlighting the need for better strategies to prevent and treat postoperative recurrence [POR]. The first step to develop such a strategy would be to define and standardise the description of POR with adequate diagnostic instruments. In this article, we will describe the different methodologies used to report POR [endoscopic, histological, radiological, biochemical, clinical, and surgical], and review their potential benefits and limitations, as well as the optimal timing of evaluation.

19.
PLoS Negl Trop Dis ; 17(12): e0011413, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38060465

RESUMO

BACKGROUND: Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment. METHODOLOGY/PRINCIPAL FINDING: We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay. CONCLUSIONS/SIGNIFICANCE: In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa.


Assuntos
Úlcera de Buruli , Doenças Transmissíveis , Mycobacterium ulcerans , Úlcera Cutânea , Humanos , Mycobacterium ulcerans/genética , Úlcera de Buruli/tratamento farmacológico , Úlcera de Buruli/microbiologia , Úlcera , Côte d'Ivoire , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/microbiologia
20.
Microbiome ; 11(1): 66, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004103

RESUMO

BACKGROUND: Crohn's disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf ΔARE mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation. RESULTS: We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including Tnf ΔARE and SAMP/Yit mice. SFB mono-colonization of germ-free Tnf ΔARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17A, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated Tnf ΔARE mice confirmed that SFB presence is indispensable for disease development. Screening of 468 ileal and colonic mucosal biopsies from adult and pediatric IBD patients, using previously published and newly designed human SFB-specific primer sets, showed no presence of SFB in human tissue samples, suggesting a species-specific functionality of the pathobiont. Simulating the human relevant therapeutic effect of exclusive enteral nutrition (EEN), EEN-like purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice, providing functional evidence for the protective mechanism of diet in modulating microbiota-dependent inflammation in IBD. CONCLUSIONS: We identified a novel pathogenic role of SFB in driving severe CD-like ileo-colonic inflammation characterized by loss of Paneth and goblet cell functions in Tnf ΔARE mice. A purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice in contrast to a fiber-containing chow diet, clearly demonstrating the important role of diet in modulating a novel IBD-relevant pathobiont and supporting a direct link between diet and microbial communities in mediating protective functions. Video Abstract.


Assuntos
Doença de Crohn , Ileíte , Adulto , Humanos , Camundongos , Animais , Criança , Doença de Crohn/microbiologia , Inflamação , Ileíte/microbiologia , Ileíte/patologia , Dieta , Bactérias/genética , Modelos Animais de Doenças
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