Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Management and Long-term Outcomes of Crohn's Disease Complicated with Enterocutaneous Fistula: ECUFIT Study from GETECCU.

BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

Gastroenterologists' attitudes on the detection and management of gastric premalignant conditions: results of a nationwide survey in Spain.

INTRODUCTION: Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists' attitudes on the detection and management of GPC. METHODS: A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología. RESULTS: The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery. CONCLUSION: There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized.

Frecuencia y aspectos clínicos del cáncer gástrico precoz en relación con el avanzado en un área sanitaria de España / Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain

INTRODUCCIÓN: En la actualidad, la incidencia del cáncer gástrico (CG) está disminuyendo, sin embargo, la supervivencia continúa siendo baja. El cáncer gástrico precoz (CGP) ofrece un mejor pronóstico y la posibilidad de tratamientos endoscópicos curativos. PACIENTES Y MÉTODOS: Estudio observacional de una cohorte retrospectiva de todos los pacientes con CG en un periodo de 5años en un área sanitaria de España. El CGP incluyó los pacientes con afectación mucosa o submucosa (T1) independientemente de la afectación ganglionar, mientras que el avanzado fueron los T2-T4. RESULTADOS: Se incluyeron 209 pacientes de los cuales 26 (12%) fueron CGP. El CGP no tuvo diferencias en comparación con el avanzado en la edad, sexo, infección por HP, lesiones premalignas ni tipo histológico; sin embargo, tuvo diferencias significativas en la localización (antro e incisura en un 76% vs. 38%, p = 0,01), síntomas de alarma (69% vs. 90%, p < 0,01), tratamiento con intención curativa (100% vs. 30%, p < 0,01), performance status (PS 0-1: 92% vs. 75%, p = 0,03) y supervivencia (85% vs. 20%, p < 0,001). Entre los pacientes tratados con intención curativa, el 98% (79/81) fueron operados y el 2% (2/81) fueron tratados con mucosectomía. Siete (27%) pacientes con CGP se hubiesen podido beneficiar de disección submucosa. DISCUSIÓN: La frecuencia del CGP fue baja en nuestra área sanitaria (12% de los CG). El CGP tuvo síntomas de alarma en un alto porcentaje, se localizó en el tercio distal del estómago (antro e incisura) y tuvo mejor pronóstico en relación con el CG avanzado. Se deben implementar medidas para incrementar la detección y tratamiento endoscópico del CGP

INTRODUCTION: Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. PATIENTS AND METHODS: Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. RESULTS: 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p = 0.01), alarm symptoms (69% vs 90%, p < 0.01), curative treatment (100% vs 30%, p < 0.01), performance status (PS 0-1: 92% vs 75%, p = 0.03) and survival (85% vs 20%, p < 0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. DISCUSSION: EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented

Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain. / Frecuencia y aspectos clínicos del cáncer gástrico precoz en relación con el avanzado en un área sanitaria de España.

INTRODUCTION: Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. PATIENTS AND METHODS: Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. RESULTS: 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p=0.01), alarm symptoms (69% vs 90%, p<0.01), curative treatment (100% vs 30%, p<0.01), performance status (PS 0-1: 92% vs 75%, p=0.03) and survival (85% vs 20%, p<0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. DISCUSSION: EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Gastric cancer missed at esophagogastroduodenoscopy in a well-defined Spanish population.

BACKGROUND: Although esophagogastroduodenoscopy (EGD) is the standard procedure for the diagnosis of gastric cancer (GC), some GCs are missed. There are no published data on the missed rate of GC in Spain. AIMS: To determine the frequency and characteristics of missed GCs and assess the quality of the EGD in a specific population with GC. METHODS: Records of all patients diagnosed with gastric adenocarcinoma between 2012 and 2016 in a defined geographic area were reviewed. Missed GC was defined as a case with a prior negative EGD for cancer. Quality indicators from the prior EGDs were measured. RESULTS: From 212 cases of GC, 25 cases were excluded. Seventeen out of 187 patients had a prior EGD (9.1%). Twelve of those 17 missed GC had a prior EGD with some abnormal findings. In 6 of them, biopsies were taken. Survival was no different between patients with missed and non-missed GC. Quality indicators that failed to meet standards were recording time, image documentation, and a protocol of biopsies. CONCLUSIONS: Missed GC in an EGD in a defined population in Spain is not uncommon (9.1%). The endoscopist is an important factor in missed GC due to lack of adequate detection and sampling error. Compliance with performance of quality indicators could reduce missed GC.