ABSTRACT
Purpose: The clinical spectrum of common variable immunodeficiency (CVID) includes predisposition to infections, autoimmune/inflammatory complications and malignancy. Liver disease is developed by a proportion of patients with CVID, but limited evidence is available about its prevalence, pathogenesis and prognostic outcome. This lack of evidence leads to the absence of guidelines in clinical practice. In this study, we aimed at defining the characteristics, course and management of this CVID complication in Spain. Methods: Spanish reference centers were invited to complete a cross-sectional survey. Thirty-eight patients with CVID-related liver disease from different hospitals were evaluated by a retrospective clinical course review. Results: In this cohort, abnormal liver function and thrombocytopenia were found in most of the patients (95% and 79% respectively), in keeping with the higher incidence of abnormal liver imaging and splenomegaly. The most common histological findings included nodular regenerative hyperplasia (NRH) and lymphocytic infiltration, which have been associated with portal hypertension (PHTN) leading to a poorer prognosis. Autoimmune/inflammatory complications occurred in 82% of the CVID patients that developed liver disease and 52% of the patients treated with immunomodulators showed a reduction in the liver function tests' abnormalities during treatment. Among the experts that conducted the survey, there was 80% or more consensus that the workup of CVID-related liver disease requires liver profile, abdominal ultrasound and transient elastography. The majority agreed that liver biopsy should be essential for diagnosis. There was 94% consensus that endoscopic studies should be performed in the presence of PHTN. However, there was 89% consensus that there is insufficient evidence on the management of these patients. Conclusion: Liver disease varies in severity and may contribute substantially to morbidity and mortality in patients with CVID. Hence the importance of close follow-up and screening of this CVID complication to prompt early targeted intervention. Further research is needed to evaluate the pathophysiology of liver disease in patients with CVID to identify personalized treatment options. This study emphasizes the urgent need to develop international guidelines for the diagnosis and management of this CVID complication.
Subject(s)
Common Variable Immunodeficiency , Hypertension, Portal , Humans , Retrospective Studies , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/therapy , Cross-Sectional Studies , Hypertension, Portal/diagnosis , Hypertension, Portal/etiology , Hypertension, Portal/therapyABSTRACT
Diffuse large B cell lymphoma (DLBCL) treatment with R-CHOP regimen produces 5-year progression-free survival and overall survival of around 60-70%. Our objective was to discover prognostic biomarkers allowing early detection of the remaining 30-40% with poor long-term outcome. For this purpose, we applied a novel strategy: from a cohort of DLBCL patients, treated with standard therapy, a discovery group of 12 patients with poor prognosis (advanced stage III-IV, R-IPI > 2) was formed, consisting of six chemoresistant (refractory/early relapse < 12 months) and six chemosensitive (complete remission > 3 years) subjects. By using microarray assays, the most differentially expressed miRNAs were defined as an initial set of prognostic miRNA candidates. Their expression was then analyzed in a validation cohort of 68 patients and the three miRNAs with the most significant impact on event-free and overall survival were selected. In the DLBCL cell line U-2932 the transfection with miR-1244 and miR-193b-5p, but not miR-1231, blocked the effect of CHOP on cell viability. A subsequent gene set enrichment analysis in patients revealed the implication of the first two miRNAs in cell cycle control and chemoresistance-related pathways, whereas the last one was involved in immunological processes. In conclusion, this novel strategy identified three promising prognostic markers for DLBCL patients at high risk of failure with standard therapy.
ABSTRACT
Although the presence of pancreatic tissue outside of the usual anatomical location of the pancreas is not an uncommon incidental finding, the risk of malignancy is extremely low. We report a case of ductal adenocarcinoma arising within a focus of heterotopic pancreas, occurring in the jejunum of an 81 year old woman. The patient presented with a history of progressive gastrointestinal occlusive symptoms. Computerized tomography showed a mass in the jejunum, which was surgically removed. Histopathology revealed an invasive pancreatic ductal adenocarcinoma from pancreatic tissue with no connection with the original gland (Heinrich type II). At the 12-month follow-up, there were no signs of recurrence. Despite the low risk of malignancy in heterotopic pancreas, adenocarcinoma is the most frequent histological type, and the prognosis is still not clear. Lesions incidentally detected during surgery and in symptomatic patients need to be removed by conservative procedures in order to exclude malignant disease
Aunque la presencia de tejido pancreático fuera del páncreas es un hallazgo incidental no infrecuente, el riesgo de malignidad es extremadamente bajo. Presentamos el caso de una mujer de 81 años de edad con historia progresiva de síntomas oclusivos gastrointestinales, que presentó en el estudio por tomografía computarizada una lesión oclusiva localizada en yeyuno. El estudio histológico reveló la presencia de un adenocarcinoma ductal invasivo de tipo pancreático sobre tejido pancreático sin conexión con la glándula original (Heinrich tipo II). En el seguimiento posterior de la paciente a 12 meses, no se observaron signos de recurrencia. A pesar de que el riesgo de malignización del páncreas heterotópico es raro, el tipo histológico más frecuente es el adenocarcinoma. El pronóstico es aún incierto. Es necesaria la resección quirúrgica de estas lesiones en el momento del diagnóstico con el fin de descartar la presencia de enfermedad maligna
Subject(s)
Humans , Female , Aged, 80 and over , Endoscopy, Gastrointestinal/methods , Carcinoma, Pancreatic Ductal/pathology , Jejunal Neoplasms/pathology , Choristoma/pathology , Islets of Langerhans/pathology , Hernia, Hiatal/complications , Neoplasm Invasiveness/pathologyABSTRACT
Although the presence of pancreatic tissue outside of the usual anatomical location of the pancreas is not an uncommon incidental finding, the risk of malignancy is extremely low. We report a case of ductal adenocarcinoma arising within a focus of heterotopic pancreas, occurring in the jejunum of an 81 year old woman. The patient presented with a history of progressive gastrointestinal occlusive symptoms. Computerized tomography showed a mass in the jejunum, which was surgically removed. Histopathology revealed an invasive pancreatic ductal adenocarcinoma from pancreatic tissue with no connection with the original gland (Heinrich type II). At the 12-month follow-up, there were no signs of recurrence. Despite the low risk of malignancy in heterotopic pancreas, adenocarcinoma is the most frequent histological type, and the prognosis is still not clear. Lesions incidentally detected during surgery and in symptomatic patients need to be removed by conservative procedures in order to exclude malignant disease.
Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Choristoma/pathology , Jejunal Neoplasms/pathology , Pancreas , Pancreatic Neoplasms/pathology , Aged, 80 and over , Carcinoma, Pancreatic Ductal/complications , Choristoma/complications , Female , Humans , Jejunal Neoplasms/complications , Neoplasm Invasiveness , Pancreatic Neoplasms/complicationsABSTRACT
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