RESUMO
BACKGROUND: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS: A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). CONCLUSIONS: There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.
Assuntos
Adenocarcinoma , Neoplasias Intestinais , Mutação , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Neoplasias Intestinais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intestino Delgado/patologia , Adulto , Prognóstico , Idoso de 80 Anos ou mais , Perfilação da Expressão Gênica , Reparo de Erro de Pareamento de DNA/genéticaRESUMO
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 JovemRESUMO
BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. METHODS: We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. RESULTS: Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. CONCLUSION: Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.
Assuntos
Colite Ulcerativa , Doença de Crohn , Infecções por HIV , Doenças Inflamatórias Intestinais , Adulto , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos RetrospectivosRESUMO
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 TratamentoRESUMO
BACKGROUND AND AIMS: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). METHODS: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. RESULTS: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. CONCLUSION: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.
Assuntos
Doenças Cardiovasculares , Colite Ulcerativa , Tromboembolia Venosa , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Estudos Transversais , Feminino , Humanos , Prevalência , Fatores de Risco , Autorrelato , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologiaRESUMO
Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next-generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. Overall, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localised tumours (72.7% vs 38.2%, P = .003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localised tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Doenças Raras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Doenças Raras/metabolismo , Doenças Raras/patologia , Receptor ErbB-2/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Proteína Smad4/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
AIM: The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. METHODS: This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. RESULTS: In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. CONCLUSION: An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.
Assuntos
Doença de Crohn , Fístula Retal , Adesivos Teciduais , Adulto , Doença de Crohn/complicações , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Fístula Retal/etiologia , Fístula Retal/terapia , Estudos Retrospectivos , Adesivos Teciduais/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: Diagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools. DESIGN: We have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes. RESULTS: Within the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated 'DGMuneS', outperformed Immunoscore when used in estimating patients' prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk. CONCLUSION: These findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients' prognosis.
Assuntos
Adenocarcinoma/patologia , Inteligência Artificial , Neoplasias do Colo/patologia , Interpretação de Imagem Assistida por Computador , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Humanos , Linfócitos do Interstício Tumoral , Invasividade Neoplásica , Estadiamento de Neoplasias , PrognósticoRESUMO
Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23-90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz-Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin-based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54-months median follow-up, the 5-year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA-resected tumours, the prognostic factors for OS were grade and T stage.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Intestinais/diagnóstico , Intestino Delgado/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , França/epidemiologia , Humanos , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/terapia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/cirurgia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. METHODS: A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. RESULTS: In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02-3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68-7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92-3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96-3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058). CONCLUSION: High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. CLINICAL TRIAL NUMBER: NCT00952029.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Indução/métodos , Idoso , Progressão da Doença , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting. MATERIALS AND METHODS: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR). RESULTS: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007). CONCLUSION: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF. IMPLICATIONS FOR PRACTICE: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
Assuntos
Anticorpos Monoclonais , Neoplasias Colorretais , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/uso terapêutico , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. METHODS: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. RESULTS: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. CONCLUSION: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia/métodos , Linite Plástica/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Linite Plástica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/terapiaRESUMO
The most commonly reported pattern of anti-PD-1 induced colitis is an active colitis characterized by neutrophilic inflammation and prominent apoptosis. On the other hand, reports of collagenous colitis (which is a microscopic colitis) are exceptional. In this report, we describe an unusual case of anti-PD1-associated collagenous colitis in a 76-year-old man, treated with pembrolizumab for a stage IV cutaneous melanoma. Fourteen months after the start of pembrolizumab, the patient developed a grade 3 diarrhea (up to 9 stools per day) associated with profound hypokalemia. No bacterial, viral or parasitological infectious agents were found from stool analysis. The rectosigmoidoscopy showed colonic diffuse congestion with no ulceration. Systematic biopsies were performed during endoscopy. Histologically, the fragments analyzed revealed a moderately thickened subepithelial collagen layer (20-30µm thick) associated with a mild mixed inflammatory infiltrate within the lamina propria. There were no granuloma lesions, ulcerations or viral inclusion bodies. The patient was initially successfully treated with corticosteroids (prednisone) and temporary interruption of pembrolizumab. However, during corticosteroids tapering, a relapse was observed. The treatment was switched to budesonide, leading to a complete and definitive resolution of diarrhea. To date, budesonide has been stopped and pembrolizumab has not been restarted. Currently, there is a bone progression treated by radiotherapy alone. In case of a more important progression, a systemic treatment will be secondarily discussed.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Colagenosa/induzido quimicamente , Melanoma/complicações , Neoplasias Cutâneas/complicações , Idoso , Budesonida/uso terapêutico , Colite Colagenosa/tratamento farmacológico , Colite Colagenosa/patologia , Diarreia/tratamento farmacológico , Diarreia/patologia , Humanos , Hipopotassemia/tratamento farmacológico , Hipopotassemia/patologia , Masculino , Melanoma/tratamento farmacológico , Prednisona/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. METHODS: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10â cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. RESULTS: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31â 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). CONCLUSIONS: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. TRIAL REGISTRATION NUMBER: IRB 001508, Paris 7 University.
Assuntos
Biópsia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Gastroenterologia , Aumento da Imagem/métodos , Doenças Inflamatórias Intestinais/complicações , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia/métodos , Colite Ulcerativa/complicações , Neoplasias Colorretais/cirurgia , Doença de Crohn/complicações , Feminino , Seguimentos , França , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Imagem de Banda Estreita , Vigilância da População/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND & AIMS: Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS: We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS: We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS: In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.
Assuntos
Doenças Autoimunes/patologia , Doenças Inflamatórias Intestinais/complicações , Pancreatite/patologia , Adulto , Bélgica , Biópsia , Estudos de Casos e Controles , Endossonografia , Feminino , França , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To determine the cumulative incidence and the prognostic factors of ileorectal anastomosis (IRA) failure after colectomy for ulcerative colitis (UC). BACKGROUND: Although ileal pouch-anal anastomosis is recommended after colectomy for UC, IRA is still performed. METHODS: This was a multicenter retrospective cohort study, which included patients with IRA for UC performed between 1960 and 2014. IRA failure was defined as secondary proctectomy and/or rectal cancer occurrence. Uni- and multivariate survival analyses were performed using Cox-proportional hazards models. RESULTS: A total of 343 patients from 13 French centers were included. Median follow up after IRA was 10.6 years. IRA failure rates were estimated at 27.0% (95% confidence interval, CI, 22-32) and 40.0% (95% CI 33-47) at 10 and 20 years, respectively. Median survival time without IRA failure was estimated at 26.8 years. Two thirds of secondary proctectomies were performed for refractory proctitis, and 20% for rectal neoplasia. Univariate analysis identified factors associated with IRA failure: IRA performed after 2005, a longer duration of disease at the time of IRA, indication for colectomy and having received immunomodulative agents before IRA. In multivariate analysis, treatment with both immunosuppressant (IS) and anti-TNF before colectomy was independently associated with IRA failure (HR=2.9, 95% CI 1.2-7.1). Conversely, colectomy for severe acute colitis was associated with decreased risk of IRA failure (HR=0.6, 95% CI 0.4-0.97). DISCUSSION: Patients with UC have a high risk of IRA failure, particularly when colectomy is performed for refractory disease. However, IRA could be discussed after colectomy for severe acute colitis, or in patients naive to IS and anti-TNF.
Assuntos
Colite Ulcerativa/cirurgia , Proctocolectomia Restauradora , Canal Anal/cirurgia , Anastomose Cirúrgica , Colite Ulcerativa/mortalidade , Doença de Crohn/diagnóstico , Seguimentos , França/epidemiologia , Humanos , Íleo/cirurgia , Complicações Pós-Operatórias , Proctite/etiologia , Modelos de Riscos Proporcionais , Reto/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVES: We sought to determine the frequency of and risk factors for early (30-day) postoperative complications after ileocecal resection in a well-characterized, prospective cohort of Crohn's disease patients. METHODS: The REMIND group performed a nationwide study in 9 French university medical centers. Clinical-, biological-, surgical-, and treatment-related data on the 3 months before surgery were collected prospectively. Patients operated on between 1 September 2010 and 30 August 2014 were included. RESULTS: A total of 209 patients were included. The indication for ileocecal resection was stricturing disease in 109 (52%) cases, penetrating complications in 88 (42%), and medication-refractory inflammatory disease in 12 (6%). A two-stage procedure was performed in 33 (16%) patients. There were no postoperative deaths. Forty-three (21%) patients (23% of the patients with a one-stage procedure vs. 9% of those with a two-stage procedure, P=0.28) experienced a total of 54 early postoperative complications after a median time interval of 5 days (interquartile range, 4-12): intra-abdominal septic complications (n=38), extra-intestinal infections (n=10), and hemorrhage (n=6). Eighteen complications (33%) were severe (Dindo-Clavien III-IV). Reoperation was necessary in 14 (7%) patients, and secondary stomy was performed in 8 (4.5%). In a multivariate analysis, corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate (odds ratio (95% confidence interval)=2.69 (1.15-6.29); P=0.022). Neither preoperative exposure to anti-tumor necrosis factor (TNF) agents (n=93, 44%) nor trough serum anti-TNF levels were significant risk factors for postoperative complications. CONCLUSIONS: In this large, nationwide, prospective cohort, postoperative complications were observed after 21% of the ileocecal resections. Corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate. In contrast, preoperative anti-TNF therapy (regardless of the serum level or the time interval between last administration and surgery) was not associated with an elevated risk of postoperative complications.
Assuntos
Ceco/cirurgia , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Íleo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Sepse/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Doenças do Ceco/etiologia , Doenças do Ceco/cirurgia , Estudos de Coortes , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Feminino , França/epidemiologia , Humanos , Doenças do Íleo/etiologia , Doenças do Íleo/cirurgia , Ileostomia , Imunossupressores/uso terapêutico , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Hemorragia Pós-Operatória/epidemiologia , Estudos Prospectivos , Reoperação , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. METHODS: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. DISCUSSION: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. TRIAL REGISTRATION: NCT02402842 , EudraCT: 2014-001789-81.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Fluoruracila/uso terapêutico , Recidiva Local de Neoplasia , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Docetaxel , França , Humanos , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Adulto JovemAssuntos
Bronquiolite Obliterante/imunologia , Colite Ulcerativa/diagnóstico , Tosse/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Biópsia , Brônquios/diagnóstico por imagem , Brônquios/imunologia , Brônquios/patologia , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/tratamento farmacológico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Tosse/diagnóstico , Tosse/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND & AIMS: Little is known about the efficacy and safety of thalidomide therapy for patients with refractory Crohn's disease (CD), particularly in respect to long-term outcomes of patients. METHODS: We conducted a retrospective multicenter observational study to evaluate thalidomide efficacy and the probability of its withdrawal because of either toxicity or lack/loss of efficacy. We analyzed data from 77 patients with active intestinal and/or perineal CD, refractory to conventional immunosuppressive therapies, treated with thalidomide at 5 tertiary referral inflammatory bowel disease centers in France. We also analyzed the long-term efficacy of thalidomide. RESULTS: Fifty-four percent of the patients were in clinical remission after thalidomide treatment within the first year. The proportions of patients from whom thalidomide was withdrawn because of lack/loss of efficacy and/or toxicity were 35% at 3 months of treatment, 69% at 12 months, and 88% at 24 months. The proportions of patients from whom thalidomide was withdrawn because of toxicity alone were 22% at 3 months, 34% at 12 months, and 46% at 24 months. Overall, neuropathy occurred in 30 patients and was the main reason for thalidomide withdrawal. CONCLUSIONS: On the basis of a retrospective multicenter observational study, thalidomide therapy is effective in most patients with refractory active intestinal and/or perineal CD. However, its toxicity limits its use as a maintenance therapy.