Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Selective granulocyte-monocyte apheresis during induction with vedolizumab in moderate-severe ulcerative colitis: Experience in a tertiary hospital.

AIM: Granulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate-severe UC and incomplete response to steroids. PATIENTS AND METHODS: Single-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded. RESULTS: The study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4-5; 3-10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39-74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378µg/g (IQR: 924-5778µg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3-113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed. CONCLUSIONS: GMA+VDZ during induction can be effective and safe in selected patients with moderate-severe UC and partial response to steroids.

Evaluation of the transition from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease. / Valoración de la transición de vedolizumab intravenoso a subcutáneo en pacientes con enfermedad inflamatoria intestinal.

AIMS: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc). METHODS: An observational, prospective, single-center cohort study was performed. Patients with inflammatory bowel disease and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. RESULTS: Forty-three patients were included, 12 of them (27.9%) chose to transition to sc formulation. All included patients remained in remission during follow-up. At week 16 no significant differences were found in terms of calprotectin levels in patients on iv treatment (mean 146.6±SD 45.9) vs. sc (159.26±53.9) (p=0.9). Vedolizumab serum levels at week 16 were higher in the sc group (22,364.3±5141.6) vs. iv (11,425.9±1514.2) (p=0.009). At week 16, 9 (75%) of the patients in the sc group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. Four patients (12.9%) in the iv group and 2 (16.6%) in the sc group presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. CONCLUSION: In our experience, vedolizumab sc is a convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.

Intensification with Intravenous Ustekinumab in Refractory Crohn's Disease.

BACKGROUND: The rates of clinical and biochemical responses in Crohn's disease (CD) patients treated with intravenous (IV) ustekinumab (UST) intensification are scarcely described. METHODS: Patients with diagnosis of CD who were under intensified IV ustekinumab treatment (130 mg every 4 weeks) were retrospectively included, evaluating the clinical and biochemical response 12 weeks after the change in treatment regimen (switch from SC to IV), as well as the serum levels of the drug. RESULTS: Twenty-seven patients, all of whom had transitioned to intensified intravenous ustekinumab treatment due to a secondary loss of response to the drug, were included in the retrospective analysis. At the baseline visit, prior to changing IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs. 2842 ng/mL, p = 0.00005). However, no significant differences were found between these two groups 12 weeks after IV intensification (7949 vs. 7937 ng/mL; p = 0.99). In patients with previous intensified UST SC, a decrease in fecal calprotectin was observed 12 weeks after starting IV intensification, going from a mean of 1463 ug/g to 751 ug/g, although the differences were not significant (p = 0.14). CONCLUSION: In our experience, intensifying treatment with IV UST leads to clinical and biochemical improvements in CD patients with a secondary loss of response to SC maintenance with this drug, and an increase in drug levels was observed 12 weeks after IV UST intensification.

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Hospitalización en enfermedad inflamatoria intestinal: perspectiva actual / Hospitalization in inflammatory bowel disease: Current perspective

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Serologic response to COVID-19 vaccines in patients with inflammatory bowel disease: a prospective study

Background and aims: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. Methods: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. Results: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. Conclusion: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious (AU)

Utilidad de la calprotectina sérica como biomarcador de actividad inflamatoria en la enfermedad inflamatoria intestinal / The use of serum calprotectin as a biomarker for inflammatory activity in inflammatory bowel disease

Introducción: para el correcto manejo de la enfermedad inflamatoria intestinal (EII) precisamos de marcadores no invasivos, fiables y sencillos que permitan detectar la actividad inflamatoria de forma precoz. Uno de estos marcadores biológicos podría ser la calprotectina sérica (CS). Material y métodos: inclusión prospectiva de pacientes con EII que iban a realizarse una colonoscopia por práctica clínica habitual. Se determinaron: CS, calprotectina fecal (CF) y parámetros analíticos convencionales. Se realizaron los índices clínicos (Harvey y Walmsley) así como los endoscópicos correspondientes en cada escenario (Simple Endoscopic Score Crohn Disease [SES-CD] y Mayo). Resultados: se incluyeron 53 pacientes; el 51% (27 pacientes) con colitis ulcerosa (CU) y el 49% (26 pacientes) con enfermedad de Crohn (EC). En CU los valores de CS fueron significativamente superiores con actividad endoscópica Mayo 2/3 (mediana 10,39 mg/ml [IQR: 7,4-12,2]) frente aquellos con Mayo 0/1 (mediana 4,07mg/ml [IQR: 2,9-7,2]) (p = 0,01). El área bajo la curva ROC (AUCROC) fue 0,85, obteniendo para un punto de corte de CS de 4,4 mg/dl una sensibilidad y especificidad del 83,3% y 81,25%, respectivamente. Además, al comparar con otros marcadores serológicos de actividad (proteína C reactiva [PCR], velocidad de sedimentación globular [VSG], hemoglobina [Hb] y plaquetas) se obtuvo un AUCROC superior. Cuando comparamos la CS con los hallazgos endoscópicos en EC, no hubo diferencias estadísticamente significativas (SES CD > 3: 20,1 [IQR: 16,8-23,4] vs. SESC ≤ 3:6,25 [IQR: 5,4-7,1]) (p = 0,8). Conclusiones: la CS es un buen marcador indirecto de la actividad inflamatoria y existe correlación con los hallazgos endoscópicos en CU, aunque sin diferencias estadísticamente significativas en EC

Introduction: simple, reliable and non-invasive biomarkers are needed to enable the early detection of inflammatory activity for the correct management of inflammatory bowel disease (IBD). One of these biomarkers may be serum calprotectin (SC). Material and methods: a prospective study was performed of patients with IBD due to undergo a colonoscopy as part of the common clinical practice. The study parameters included SC, fecal calprotectin (FC) and conventional blood test parameters. Clinical indices (Harvey and Walmsley) and relevant endoscopic scores were completed for each scenario (Simple Endoscopic Score Crohn Disease [SES-CD] and Mayo). Results: fifty-three patients were included in the study, 51% (27 patients) with ulcerative colitis (UC) and 49% (26 patients) with Crohn's disease (CD). The CS values in UC were significantly higher with an endoscopic Mayo score 2/3 (median score 10.39 mg/ml [IQR: 7.4-12.2]) compared to those with a Mayo score of 0/1 (median 4.07 mg/ml [IQR: 2.9-7.2]) (p = 0.01). The area under the ROC curve (AUCROC) was 0.85 and the sensitivity and specificity were 83.3% and 81.25%, respectively, for a SC cut-off point of 4.4 mg/dl. Furthermore, a higher AUCROC was obtained in comparison with other serological markers for activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], hemoglobin [Hb] and platelets). There were no statistically significant differences in the comparison between SC and endoscopic findings in CD (SES CD > 3: 20.1 [IQR: 16.8-23.4] vs SESC ≤ 3:6.25 [IQR: 5.4-7.1]) (p = 0.8). Conclusions: SC is a good indirect marker of inflammatory activity and there was a correlation with endoscopic findings in UC. However, there were no statistically significant differences in the case of CD

Dilatación con balón asociada a esfinterotomía, evaluación de eficacia y seguridad en un hospital terciario / Safety and efficacy of large balloon sphincteroplasty in a third care hospital

Introducción y objetivos: la dilatación con balón de gran tamaño asociada a esfinterotomía es un recurso cada vez más utilizado en la extracción de coledocolitiasis de gran tamaño. El objetivo de este estudio es evaluar la eficacia y seguridad de la dilatación con balones mayores de 10 mm en un entorno de práctica clínica habitual. Pacientes y métodos: estudio prospectivo en un hospital terciario. Todos los pacientes en los que se realizó dilatación con balón mayor de 10 mm asociado a esfinterotomía entre julio de 2007 y marzo de 2011 se incluyeron prospectivamente en una base de datos incluyendo aspectos clínicos, del procedimiento, resultados y complicaciones. El éxito del procedimiento se definió como la extracción de todos los cálculos presentes documentada como ausencia de defectos de repleción en la colangiografía final y la ausencia de signos clínicos y/o radiológicos tras la CPRE sugestivos de persistencia de litiasis. La presencia de pancreatitis, colangitis, perforación y hemorragia post-CPRE también se documentó. Resultados: se realizaron 120 procedimientos en 109 pacientes diferentes, con balones entre 10 y 20 mm de diámetro. La tasa de éxito fue del 91% en el primer intento y del 96,7% tras dos procedimientos. La litotricia mecánica solo se necesitó en un caso (0,8%). La tasa de complicaciones fue del 4,2% debido a cinco casos de hemorragia post-CPRE en pacientes de alto riesgo de sangrado. Conclusión: la dilatación con balón asociada a esfinterotomía en condiciones de práctica clínica habitual muestra una tasa de éxito excelente con un índice de complicaciones reducido(AU)

Background and aims: large balloon sphincteroplasty (LBS) associated with sphincterotomy (ES) has gained acceptance as a useful tool in extracting difficult bile duct stones. Our purpose was to evaluate the efficacy and safety of LBS with balloons >=10 mm in clinical practice setting. Patients and methods: unicentre prospective study in a tertiary care hospital. All patients who underwent LBS associated with ES between July 2007 and March 2011 were included prospectively in a database recording clinical aspects, procedure data, outcome and complications. Success is the main outcome defined as complete stone removal documented by absence of any filling defect during a final occlusion cholangiogram and absence of clinical or radiological findings after the ERCP consistent with remaining stones. Complications as pancreatitis, cholangitis, post-ERCP bleeding, perforation and others were also measured. Results: one hundred twenty procedures were made in 109 patients with balloons ranging from 10 to 20 mm. Success rate was 91% in the first attempt and 96.7% after two procedures. Mechanical lithotripsy was only needed in one case (0.8%). Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk patients. Conclusion: large balloon sphincteroplasty associated to sphincterotomy in clinical practice is a very effective and safe technique(AU)

Uso de gadolinio como contraste en CPRE en pacientes con reacciones adversas a contrastes yodados / Use of gadolinium as contrast agent in endoscopic retrograde cholangiopancreatography in patients with iodine allergy

Introducción Para la realización de colangiopancreatografía retrógrada endoscópica (CPRE) es necesario el uso de contrastes radiológicos, utilizándose habitualmente contrastes yodados. La pauta de actuación ante pacientes que han sufrido reacciones adversas a contrastes yodados y que van a recibir una CPRE es controvertida. Objetivo Evaluar la seguridad y eficacia de un contraste basado en gadolinio en pacientes con reacciones alérgicas previas a contrastes yodados durante la realización de CPRE. Material y métodos Se utilizó gadobutrol como agente de contraste, un compuesto basado en el gadolinio, sin utilizar profilaxis previa. Se realizaron 13 procedimientos en 11 pacientes con antecedentes de reacciones adversas previas a contrastes yodados. Resultados Las CPRE fueron completadas satisfactoriamente en todos los casos, obteniéndose 13 colangiogramas y un pancreatograma. La calidad de imagen obtenida fue buena, equiparable a la obtenida con los contrastes yodados utilizados habitualmente, y permitiendo realizar el diagnóstico y la terapéutica endoscópica sin suponer una limitación. No se encontraron efectos adversos relacionados con el contraste y tampoco complicaciones post-CPRE. Conclusiones El gadobutrol, un contraste basado en gadolinio, es una alternativa segura y eficaz en pacientes alérgicos a contrastes yodados(AU)

Introduction Radiologic contrasts are required during endoscopic retrograde cholangiopancreatography (ERCP). The most frequently used are iodine-based contrast media. Controversy still surrounds the optimal strategy in patients with previous adverse reactions to iodine contrasts that need to undergo an ERCP. Objective To evaluate the safety and efficacy of a gadolinium-derived contrast medium in patients with previous reactions to iodine-derived agents during ERCP. Material and methods Thirteen ERCP were performed in 11 patients with well-established adverse reactions to iodine compounds. ERCP was carried out with gadobutrol, a non-ionic gadolinium compound and without prophylaxis. Results In all patients, ERCP were satisfactorily completed. Thirteen cholangiograms and one pancreatogram were obtained. All procedures were technically successful, allowing diagnosis and endotherapy. The quality of the images was good, similar to those obtained with standard contrast media, and did not represent a limitation. No contrast-related adverse events were observed, and there were no post-ERCP complications. Conclusions Gadolinium-derived agents are a safe and effective alternative in iodine-allergic patients (AU)

Carcinoma de células en anillo de sello de la ampolla de Vater / Signet ring cell carcinoma of the ampulla of Vater

Introducción El carcinoma de células en anillo de sello de la ampolla de Vater es una entidad infrecuente, con menos de 20 casos descritos en la literatura. El objetivo de este artículo es presentar dos pacientes con esta patología y realizar una revisión de los estudios previos. Observación clínica Los dos pacientes ingresaron por ictericia obstructiva. En la ecografía y la tomografía computarizada abdominales se apreció una dilatación de la vía biliar intra y extrahepática. En la duodenoscopia, se visualizó una masa excrecente de la ampolla de Vater que, histológicamente, presentaba células con características típicas de células en anillo de sello. Se realizaron una duodenopancreatectomía cefálica con linfadenectomía y una pancreatectomía total respectivamente. Discusión El carcinoma de células en anillo de sello de la ampolla de Vater ha sido descrito únicamente en casos aislados en la literatura. Por este motivo, sus características clínicopatológicas y su pronóstico aún no están bien definidos (AU)

Introduction: Signet ring cell carcinoma of the ampulla of Vater is a rare entity and less than20 cases have been described in the literature. We report the cases of two patients with thisdisease and provide a literature review of previous studies. Case report: We describe two patients with obstructive jaundice. Abdominal ultrasonographyand abdominal computed tomography showed dilatation of the intrahepatic and common bileduct. Duodenoscopy indicated a protruding mass on the ampulla of Vater. Histopathologicalexamination showed round cells and their nuclei were located on one side with prominentsignet-ring features. One patient underwent a cephalic pancreatoduodenectomy with lymphadenectomyand the other a total pancreatectomy. Discussion: Signet ring cell carcinoma of the ampulla of Vater has only been described in isolatedcases in the literature. Therefore, the clinicopathological features and prognosis of this diseasehave not yet been well defined (AU)

Creación de ascitis artificial para el tratamiento mediante radiofrecuencia percutánea del hepatocarcinoma cercano al diafragma / Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma adjacent to the diaphragm

La cirugía constituye la primera línea de tratamiento curativo en el hepatocarcinoma (CHC). Sin embargo, una gran mayoría no se puede beneficiar de la misma debido al avanzado estadio tumoral, disfunción hepática severa o mala condición clínica. Por ello, se han introducido varias técnicas de ablación guiadas por imagen. Entre ellas, la radiofrecuencia percutánea (RFp) constituye una alternativa eficaz como tratamiento curativo. Sin embargo, la localización de la lesión cerca de estructuras como el diafragma o el tracto gastrointestinal, limita esta técnica debido al riego de daño térmico colateral y a un tratamiento incompleto por mala visualización. La introducción de ascitis artificial previa puede separar el CHC de los órganos adyacentes y mejorar la ventana acústica. El objetivo de este estudio fue evaluar la viabilidad, seguridad y eficacia de la RFp con ascitis artificial para el tratamiento del CHC adyacente al diafragma (AU)

Surgical resection is the first-line curative treatment of hepatocellular carcinoma (HCC). However most patients are unable to undergo surgical resection because of advanced tumoral stage, severe liver dysfunction or poor clinical status. Therefore, image-guided tumor ablation techniques have been introduced for the treatment of unresectable HCC. Among them, radiofrequency ablation (RFA) has been demonstrated to be an effective alternative curative therapy. However, local ablative therapy for tumors located close to structures such as the diaphragm or gastrointestinal tract is technically challenging because of the risk of collateral thermal damage to nearby structures or incomplete treatment of the HCC resulting from poor visibility on sonography. The introduction of artificial ascites can separate adjacent organs from the tumor and improve the sonic window. The aim of this study was to evaluate the feasibility, safety and efficacy of RFA with artificial ascites for HCC adjacent to the diaphragm (AU)