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BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.
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Absceso Abdominal , Productos Biológicos , Enfermedad de Crohn , Humanos , Masculino , Adulto , Femenino , Adalimumab/uso terapéutico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Estudios Prospectivos , Absceso/tratamiento farmacológico , Resultado del Tratamiento , Absceso Abdominal/tratamiento farmacológico , Recurrencia , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND AND STUDY AIM: Zenker's diverticulum is a rare disease that affects quality of life due to dysphagia and regurgitation. This condition can be treated by various surgical or endoscopic methods. PATIENTS AND METHOD: Patients treated for Zenker's diverticulum in three centers in the south of France between 2014 and 2019 were included. The primary objective was clinical efficacy. Secondary objectives were technical success, morbidities, recurrences, and need for a new procedure. RESULTS: One hundred forty-four patients with a total of one hundred sixty-five procedures performed were included. A significant difference was found between the different groups in terms of clinical success (97% for open surgery versus 79% for rigid endoscopy versus 90% for flexible endoscopy, p = 0.009). Technical failure occurred more frequently in the rigid endoscopy group than in the flexible endoscopy and surgical groups (p = 0.014). Median procedure duration, median time to resumption of feeding, and hospital discharge were statistically shorter for endoscopies than for open surgery. On the other hand, more recurrences occurred in patients treated by endoscopy than those treated by surgery, and more reinterventions were required. CONCLUSION: Flexible endoscopy appears to be as effective and safe as open surgery in the treatment of Zenker's diverticulum. Endoscopy allows a shorter hospital stay at the expense of a higher risk of recurrence of symptoms. It could be used as an alternative to open surgery for the treatment of Zenker's diverticulum, especially in frail patients.
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Divertículo de Zenker , Humanos , Divertículo de Zenker/complicaciones , Divertículo de Zenker/cirugía , Estudios Retrospectivos , Calidad de Vida , Endoscopía , Endoscopía Gastrointestinal , Resultado del Tratamiento , Recurrencia , Esofagoscopía/métodosRESUMEN
BACKGROUND & AIMS: It is a challenge to manage patients with ulcerative proctitis (UP) refractory to standard therapy. We investigated the effectiveness of tumor necrosis factor (TNF) antagonists in a large cohort of patients with refractory UP. METHODS: We conducted a nationwide retrospective cohort study of 104 consecutive patients with active UP refractory to conventional therapies, treated at 1 of 15 centers in France or 1 center in Belgium (the GETAID cohort). Patients received at least 1 injection of anti-TNF (infliximab, adalimumab, golimumab) from October 2006 through February 2017. Clinical response was defined as significant improvement in UC-related symptoms, and remission as complete disappearance of UC-related symptoms, each determined by treating physicians. We collected demographic, clinical, and treatment data. The median duration of follow-up was 24 months (interquartile range, 13-51 months). The primary outcome was clinical response of UP to anti-TNF treatment. RESULTS: Overall, 80 patients (77%) had a clinical response to anti-TNF therapy and 52 patients (50%) achieved clinical remission. Extra-intestinal manifestations (odds ratio OR, 0.24; 95% CI, 0.08-0.7), ongoing treatment with topical steroids (OR, 0.14; 95% CI, 0.03-0.73), and ongoing treatment with topical 5-aminosalycilates (OR, 0.21; 95% CI, 0.07-0.62) were significantly associated with the absence of clinical remission. Sixty percent (38/63) of the patients who had endoscopic assessment during follow up had mucosal healing. Among the overall population (n = 104), the cumulative probabilities of sustained clinical remission were 87.6% ± 3.4% at 1 year and 74.7% ± 4.8% at 2 years. CONCLUSIONS: In a retrospective study of 104 patients with refractory UP, anti-TNF therapy induced clinical remission in 50% and mucosal healing in 60%. About two thirds of the patients were still receiving anti-TNF therapy at 2 years.
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Colitis Ulcerosa , Proctitis , Adalimumab/uso terapéutico , Humanos , Infliximab , Proctitis/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfaRESUMEN
INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.
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Antiinflamatorios/uso terapéutico , Enfermedades del Ano/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fístula Rectal/tratamiento farmacológico , Ustekinumab/uso terapéutico , Absceso , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades del Ano/fisiopatología , Estudios de Cohortes , Enfermedad de Crohn/fisiopatología , Supervivencia sin Enfermedad , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fístula Rectal/fisiopatología , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Nearly 20% of patients who undergo hiatal hernia (HH) repair and anti-reflux surgery (ARS) report recurrent HH at long-term follow-up and may be candidates for redo surgery. Current literature on redo-ARS has limitations due to small sample sizes or single center experiences. This type of redo surgery is challenging due to rare but severe complications. Furthermore, the optimal technique for redo-ARS remains debatable. The purpose of the current multicenter study was to review the outcomes of redo-fundoplication and to identify the best ARS repair technique for recurrent HH and gastroesophageal reflux disease (GERD). METHODS: Data on 975 consecutive patients undergoing hiatal hernia and GERD repair were retrospectively collected in five European high-volume centers. Patient data included demographics, BMI, techniques of the first and redo surgeries (mesh/type of ARS), perioperative morbidity, perioperative complications, duration of hospitalization, time to recurrence, and follow-up. We analyzed the independent risk factors associated with recurrent symptoms and complications during the last ARS. Statistical analysis was performed using GraphPad Prism® and R software®. RESULTS: Seventy-three (7.49%) patients underwent redo-ARS during the last decade; 71 (98%) of the surgeries were performed using a minimally invasive approach. Forty-two (57.5%) had conversion from Nissen to Toupet. In 17 (23.3%) patients, the initial Nissen fundoplication was conserved. The initial Toupet fundoplication was conserved in 9 (12.3%) patients, and 5 (6.9%) had conversion of Toupet to Nissen. Out of the 73 patients, 10 (13%) underwent more than one redo-ARS. At 8.5 (1-107) months of follow-up, patients who underwent reoperation with Toupet ARS were less symptomatic during the postoperative period compared to those who underwent Nissen fundoplication (p = 0.005, OR 0.038). Patients undergoing mesh repair during the redo-fundoplication (21%) were less symptomatic during the postoperative period (p = 0.020, OR 0.010). The overall rate of complications (Clavien-Dindo classification) after redo surgery was 11%. Multivariate analysis showed that the open approach (p = 0.036, OR 1.721), drain placement (p = 0.0388, OR 9.308), recurrence of dysphagia (p = 0.049, OR 8.411), and patient age (p = 0.0619, OR 1.111) were independent risk factors for complications during the last ARS. CONCLUSIONS: Failure of ARS rarely occurs in the hands of experienced surgeons. Redo-ARS is feasible using a minimally invasive approach. According to our study, in terms of recurrence of symptoms, Toupet fundoplication is a superior ARS technique compared to Nissen for redo-fundoplication. Therefore, Toupet fundoplication should be considered in redo interventions for patients who initially underwent ARS with Nissen fundoplication. Furthermore, mesh repair in reoperations has a positive impact on reducing the recurrence of symptoms postoperatively.
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Fundoplicación/métodos , Reflujo Gastroesofágico/cirugía , Laparoscopía/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Recurrencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
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.
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Enfermedades Autoinmunes/patología , Enfermedades Inflamatorias del Intestino/complicaciones , Pancreatitis/patología , Adulto , Bélgica , Biopsia , Estudios de Casos y Controles , Endosonografía , Femenino , Francia , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE OF REVIEW: To review recent findings regarding eosinophilic enteritis, including epidemiology, pathogenesis, natural history, and treatment. RECENT FINDINGS: A 2017 population-based study using a US healthcare system database identified 1820 patients with a diagnosis of eosinophilic enteritis among 35,826,830 individuals. The majority of patients with eosinophilic enteritis in this study were women (57.7%), Caucasian (77.5%), and adults (> 18 years of age) (83.5%). The overall prevalence of eosinophilic enteritis was estimated at 5.1/100,000 persons. Eosinophilic enteritis, also known as eosinophilic gastroenteritis, is a rare primary eosinophilic gastrointestinal disorder (EGID) of unknown etiology characterized by the presence of an intense eosinophilic infiltrate on histopathological examination of the intestinal mucosa. The etiology of eosinophilic enteritis remains unknown. However, there is evidence to support the role of allergens in the pathogenesis of this disorder, as children and adults with EGIDs often have positive skin testing to food allergens and a family history of allergic diseases. Recent studies unraveling the role of IgE-mediated but also delayed Th2-type responses have provided insight into the pathogenesis of this disease. Eosinophilic enteritis causes a wide array of gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, bloating, or ascites, and its diagnosis requires a high degree of clinical likelihood, given the nonspecific clinical presentation and physical examination findings. Oral corticosteroids are considered to be the mainstay of treatment and are generally used for a short period with good response rates. Antihistamine drugs and sodium cromoglycate have also been used to treat patients with eosinophilic enteritis. Preliminary studies have demonstrated the potential benefit of biological therapies targeting the eosinophilic pathway such as mepolizumab, an anti-IL5 antibody, or omalizumab, an anti-IgE monoclonal antibody. Eosinophilic enteritis is generally considered to be a benign disease without relapse, but up to 50% of patients may present a more complex natural history characterized by unpredictable relapses and a chronic course.
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Enteritis/diagnóstico , Enteritis/tratamiento farmacológico , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Azatioprina/uso terapéutico , Productos Biológicos/uso terapéutico , Enteritis/epidemiología , Enteritis/etiología , Eosinofilia/epidemiología , Eosinofilia/etiología , Gastritis/epidemiología , Gastritis/etiología , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Environmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis of case-control and cohort studies on the association between vaccination and the risk for IBD. METHODS: Studies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria. RESULTS: Eleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32). CONCLUSIONS: Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.
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Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/epidemiología , Vacunación/efectos adversos , Humanos , Medición de RiesgoRESUMEN
BACKGROUND & AIMS: Colonic strictures complicate inflammatory bowel disease (IBD) and often lead to surgical resection to prevent dysplasia or cancer. We assessed the frequency of dysplasia and cancer among IBD patients undergoing resection of a colorectal stricture. METHODS: We analyzed data from the Groupe d'études et thérapeutiques des affections inflammatoires du tube digestif study. This was a nationwide retrospective study of 12,013 patients with IBD in France who underwent surgery for strictures at 16 centers from August 1992 through January 2014 (293 patients for a colonic stricture, 248 patients with Crohn's disease, 51% male, median age at stricture diagnosis of 38 years). Participants had no preoperative evidence of dysplasia or cancer. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. RESULTS: When patients were diagnosed with strictures, they had IBD for a median time of 8 years (3-14). The strictures were a median length of 6 cm (4-10) and caused symptoms in 70% of patients. Of patients with Crohn's disease, 3 (1%) were found to have low-grade dysplasia, 1 (0.4%) was found to have high-grade dysplasia, and 2 (0.8%) were found to have cancer. Of patients with ulcerative colitis, 1 (2%) had low-grade dysplasia, 1 (2%) had high-grade dysplasia, and 2 (5%) had cancer. All patients with dysplasia or cancer received curative surgery, except 1 who died of colorectal cancer during the follow-up period. No active disease at time of surgery was the only factor associated with dysplasia or cancer at the stricture site (odds ratio, 4.86; 95% confidence interval, 1.11-21.27; P = .036). CONCLUSIONS: In a retrospective study of patients with IBD undergoing surgery for colonic strictures, 3.5% were found to have dysplasia or cancer. These findings can be used to guide management of patients with IBD and colonic strictures.
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Neoplasias del Colon/epidemiología , Constricción Patológica/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Lesiones Precancerosas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND STUDY AIMS: Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment. PATIENTS AND METHODS: This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis. RESULTS: A total of 110 patients were included, of whom 6 (5.5â%) healed spontaneously, 81 (73.6â%) healed following endoscopic treatment, and 19 (17.3â%) healed following surgery. Healing rates following endoscopic treatment were 84.4â% in the first 6 months of treatment (65/77), 52.4â% for treatment lasting 6â-â12 months (11/21), and 41.7â% after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6â%). A total of 177 esogastric stents were placed in 88 patients (80.0â%). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval <â21 days between fistula diagnosis and first endoscopy (Pâ=â0.003), small fistula (Pâ=â0.01), interval between LSG and fistula ≤â3 days (Pâ=â0.01), no history of gastric banding (Pâ=â0.04). CONCLUSION: Endoscopic treatment facilitated healing of post-LSG fistula in 74â% of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered.
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Fístula del Sistema Digestivo/terapia , Endoscopía del Sistema Digestivo/métodos , Gastrectomía , Laparoscopía , Complicaciones Posoperatorias/terapia , Adolescente , Adulto , Anciano , Fístula del Sistema Digestivo/etiología , Femenino , Estudios de Seguimiento , Gastrectomía/métodos , Humanos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Eosinophilic enteritis, also known as eosinophilic gastroenteritis, is a rare primary eosinophilic gastrointestinal disorder (EGID) of unknown etiology characterized by the presence of an intense eosinophilic infiltrate on histopathology of the intestinal mucosa. KEY MESSAGES: The etiology of eosinophilic enteritis remains obscure. There is growing evidence to support the role of aeroallergens and food allergens in the pathogenesis of this disorder as children and adults with EGIDs often have positive skin testing for food allergens and a familial history of allergic diseases. Moreover, significant progress has been made in elucidating that EGIDs involve mechanisms that fall between pure IgE-mediated and delayed Th2 type responses. Preclinical studies have identified a contributory role for the cytokine IL-5 and eotaxin chemokines, providing a rationale for specific disease therapy. Eosinophilic enteritis causes a wide array of gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, bloating or ascites, and its diagnosis requires a high degree of clinical likelihood given the nonspecific presentation and physical examination findings. The Klein classification arbitrarily divided patients with eosinophilic enteritis into those with predominantly mucosal, muscle layer or subserosal disease relying on the concept that clinical presentation is dependent on the predominant involved layer of the gastrointestinal tract. Main therapeutic options are represented by oral corticosteroids for a short period with good efficacy. Antihistaminic drugs and sodium cromoglycate have also been used to treat patients with eosinophilic enteritis. CONCLUSION: Eosinophilic enteritis is generally considered as a benign disease with no relapse, but half of the patients may present a more complex natural history characterized by unpredictable relapses and a chronic course.
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Enteritis/patología , Eosinofilia/patología , Gastritis/patología , Gastroenteritis/patología , Progresión de la Enfermedad , Enteritis/diagnóstico , Enteritis/epidemiología , Enteritis/etiología , Eosinofilia/diagnóstico , Eosinofilia/epidemiología , Eosinofilia/etiología , Gastritis/diagnóstico , Gastritis/epidemiología , Gastritis/etiología , Gastroenteritis/diagnóstico , Gastroenteritis/epidemiología , Gastroenteritis/etiología , HumanosRESUMEN
TLR3 signaling is activated by dsRNA, a virus-associated molecular pattern. Injection of dsRNA into mice induced a rapid, dramatic, and reversible remodeling of the small intestinal mucosa with significant villus shortening. Villus shortening was preceded by increased caspase 3 and 8 activation and apoptosis of intestinal epithelial cells (IECs) located in the mid to upper villus with ensuing luminal fluid accumulation and diarrhea because of an increased secretory state. Mice lacking TLR3 or the adaptor molelcule TRIF mice were completely protected from dsRNA-induced IEC apoptosis, villus shortening, and diarrhea. dsRNA-induced apoptosis was independent of TNF signaling. Notably, NF-κB signaling through IκB kinase ß protected crypt IECs but did not protect villus IECs from dsRNA-induced or TNF-induced apoptosis. dsRNA did not induce early caspase 3 activation with subsequent villus shortening in mice lacking caspase 8 in IECs but instead caused villus destruction with a loss of small intestinal surface epithelium and death. Consistent with direct activation of the TLR3-TRIF-caspase 8 signaling pathway by dsRNA in IECs, dsRNA-induced signaling of apoptosis was independent of non-TLR3 dsRNA signaling pathways, IL-15, TNF, IL-1, IL-6, IFN regulatory factor 3, type I IFN receptor, adaptive immunity, as well as dendritic cells, NK cells, and other hematopoietic cells. We conclude that dsRNA activation of the TLR3-TRIF-caspase 8 signaling pathway in IECs has a significant impact on the structure and function of the small intestinal mucosa and suggest signaling through this pathway has a host protective role during infection with viral pathogens.
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Proteínas Adaptadoras del Transporte Vesicular/fisiología , Caspasa 8/fisiología , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Poli I-C/toxicidad , Receptor Toll-Like 3/fisiología , Proteínas Adaptadoras del Transporte Vesicular/deficiencia , Animales , Muerte Celular/efectos de los fármacos , Muerte Celular/inmunología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Mucosa Intestinal/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , ARN Viral/toxicidad , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Receptor Toll-Like 3/deficienciaRESUMEN
BACKGROUND: Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). METHODS: From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. RESULTS: Among 1850 included patients (65.9% with Crohn's disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size <0.5). From patients' acceptability perspective, superiority and noninferiority cutoff values should be 15% and 5%, respectively. CONCLUSIONS: Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.
Considering both the route of medication delivery and the interval between 2 administrations, we observed a strong impact of patients' experience regarding previous treatments. The most accepted maintenance regimens were subcutaneous injections with interval ≥8 weeks and oral intake.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Médicos , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Administración Intravenosa , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológicoRESUMEN
BACKGROUND/AIMS: The etiology of IBD is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC). The aim of this review was to compel the evidence for the use of antibiotics in the treatment of IBD. METHODS: We performed a systematic review of the literature regarding the use of antibiotics for inducing or maintaining remission in IBD. RESULTS: Current data are conflicting, but a recent systematic review of randomized controlled trials has shown a statistically significant effect of antibiotics being superior to placebo for active, perianal and quiescent CD and for active UC. These data have been poorly translated in clinical practice and the place of antibiotics is restricted to certain specific situations in the international guidelines. This is first linked to the difficulties in interpreting clinical trials because of their heterogeneity in study design, endpoints, type of antibiotic and concomitant therapies. The exception to this is the use of either ciprofloxacin or metronidazole for treating CD perianal fistulas. CONCLUSION: The pathology of CD, the likely primary and known secondary pathogens in this disease and the successful responses in animal models all plead for new trials of antibiotics in IBD. This is a call to select patients more carefully, and to continue antibiotics for longer than is customary. Beside antibiotics, new therapeutic approaches that can balance gut dysbiosis should be tested.
Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/microbiología , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/microbiología , Directrices para la Planificación en Salud , Humanos , Enfermedades Inflamatorias del Intestino/cirugía , Reservoritis/tratamiento farmacológicoRESUMEN
BACKGROUND: Postoperative pancreatic fistula (POPF) is a common and serious complication after distal pancreatectomy (DP). An effective and accepted score to predict the occurrence of clinically relevant (CR-) postoperative pancreatic fistula (POPF) does not exist. METHODS: Data regarding 103 consecutive patients undergoing DP from 2015 to 2019 were collected. A multivariate logistic regression was performed, in order to build a simplified score. The accuracy in predicting a categorical outcome was evaluated using the receiver operating characteristic (ROC) curves. Youden's J test was performed to evaluate the performance of a positive score on the POPF occurrence. RESULTS: Thirty-three patients developed a CR-POPF. Based on multivariate analysis results, a 4 points score was created by assigning 1 point if operation time was >4 hours, amylase levels on drains' fluid >500 UI on POD 3, pancreatic thickness >10 mm and if the BMI was >30. The discriminating ability was tested on the ROC curve, showing an area under the curve of 0.83 (95% CI: 0.75-0.92). The score threshold was determined at 2 points/4, the highest value according to the Youden Index (0.53). The sensitivity is calculated at 82% (95% CI: 69-95) and the specificity at 71 (95% CI: 61-82). A threshold of 3 points/4 allows to reach a specificity of 99% (95% CI: 99-100). CONCLUSIONS: An easy-to-use postoperative score based on operation time, obesity, amylase level on drains on POD3 and pancreatic thickness on preoperative CT seems to predict the risk of developing CR-POPF.
Asunto(s)
Pancreatectomía , Fístula Pancreática , Amilasas , Humanos , Páncreas/cirugía , Pancreatectomía/efectos adversos , Fístula Pancreática/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disorder; little is known about its natural history. We determined the clinical features and long-term outcomes of patients with EGE. METHODS: We reviewed files from 43 patients diagnosed with EGE who were followed from January 1988 to April 2009. The diagnosis was made according to standard criteria after other eosinophilic gastrointestinal disorders were excluded. We analyzed data on initial clinical presentation and long-term outcomes. RESULTS: EGE was classified as mucosal, subserosal, or muscular in 44%, 39%, and 12% of cases, respectively. Disease location was mostly duodenal (62%), ileal (72%), or colonic (88%); it was less frequently esophageal (30%) or gastric (38%). Blood eosinophilia (numbers >500/mm(3)) was observed in 74% of cases. Spontaneous remission occurred in 40% of patients; the majority of treated patients (74%) received oral corticosteroids, which were effective in most cases. After a median follow-up period of 13 years (0.8-29 years), we identified 3 different courses of disease progression: 18 patients (42%; 9 with subserosal disease) had an initial flare of the disease without relapse, 16 (37%) had multiple flares that were separated by periods of full remission (recurring disease), and 9 (21%) had chronic disease. CONCLUSIONS: The clinical presentation of EGE is heterogeneous and varies in histologic pattern; about 40% of patients resolve the disease spontaneously, without relapse. Approximately 50% have a more complex disease, which is characterized by unpredictable relapses and a chronic course.
Asunto(s)
Enteritis/patología , Eosinofilia/patología , Gastritis/patología , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Enfermedad Crónica , Enteritis/terapia , Eosinofilia/terapia , Femenino , Gastritis/terapia , Humanos , Masculino , Persona de Mediana Edad , Remisión Espontánea , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. AIMS: To assess the real-world effectiveness and safety of ustekinumab in patients with UC. METHODS: From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. RESULTS: We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti-TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid-free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3-10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. CONCLUSION: After 52 weeks, over one-half of patients with refractory UC were still treated by ustekinumab and one-third were in steroid-free clinical remission.
Asunto(s)
Colitis Ulcerosa , Ustekinumab , Adulto , Estudios de Cohortes , Colitis Ulcerosa/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Resultado del Tratamiento , Ustekinumab/efectos adversosRESUMEN
BACKGROUND: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. AIMS: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. METHODS: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti-TNF treatment during pregnancy. RESULTS: Seventy-three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti-TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti-TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. CONCLUSION: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs.
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Enfermedades Inflamatorias del Intestino , Ustekinumab , Anticuerpos Monoclonales Humanizados , Estudios de Cohortes , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa , Ustekinumab/efectos adversosRESUMEN
BACKGROUND AND AIM: It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued. METHODS: This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019. Consecutive patients with IBD, who were in steroid-free clinical remission for at least 3 months and were treated with vedolizumab for at least 6 months, were included at the time of vedolizumab discontinuation. RESULTS: A total of 95 patients [58 with Crohn's disease] discontinued vedolizumab after a median duration of therapy of 17.5 [10.6-25.4] months. After a median follow-up period of 11.2 [5.8-17.7] months, 61 [64%] patients experienced disease relapse. The probabilities of relapse-free survival were 83%, 59%, and 36% at 6, 12, and 18 months, respectively. According to the multivariate analysis, a C-reactive protein level less than 5 mg/L at vedolizumab discontinuation (hazard ratio [HR] = 0.56, 95% confidence interval [CI] [0.33-0.95], p = 0.03) and discontinuation due to patients' elective choice (HR = 0.41, 95% CI [0.21-0.80], p = 0.009) were significantly associated with a lower risk of relapse. Re-treatment with vedolizumab was noted in 24 patients and provided steroid-free clinical remission in 71% and 62.5% at Week 14 and after a median follow-up of 11.0 [5.4-13.3] months, respectively, without any infusion reactions. CONCLUSIONS: In this retrospective study, two-thirds of patients with IBD treated with vedolizumab experienced relapse within the first year after vedolizumab discontinuation. Re-treatment with vedolizumab was effective in two-thirds of patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Adulto , Proteína C-Reactiva/metabolismo , Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Deprescripciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Prioridad del Paciente , Recurrencia , Inducción de Remisión , Retratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but few real-world data are currently available. AIM: To assess short-term effectiveness and safety of ustekinumab in patients with UC. METHODS: From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (partial Mayo Clinic score ≤2) at weeks 12-16 without a rectal bleeding subscore >1. RESULTS: Among the 103 patients included, 70% had been previously exposed to ≥2 anti-TNF agents and 85% to vedolizumab. At weeks 12-16, steroid-free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12-16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti-TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid-free clinical remission at weeks 12-16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. CONCLUSION: In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid-free clinical remission in one-third of cases at weeks 12-16. Clinical severity and previous use of anti-TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12-16.