In situ follicular neoplasia in a young post-liver transplant patient.
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ABSTRACT:
SUBMITTER: Dobson R
PROVIDER: S-EPMC10107664 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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In situ follicular neoplasia in a young post-liver transplant patient.
Dobson Rachel R Venkatraman Lakshmi L Cucco Francesco F Chen Zi Z Jones Jennifer J Quinn Michael M Du Ming-Qing MQ
Pathology international 20221212 1
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Project description:In situ follicular neoplasia (ISFN) is usually an occasional incidental finding in lymph nodes by BCL2 immunohistochemistry, and its true scale is unknown. We have identified six cases of follicular lymphoma (FL) with a history of solid neoplasm 4-16 years ago, from which ISFN was identified widely in the surgically cleared lymph nodes (LNs). Using clone-specific PCR and BaseScope in situ hybridisation with primers or probes specific to the VDJ or BCL2-IGHJ junction sequence, we confirmed the clonal identity among different ISFNs and overt-FL in each of the four cases successfully investigated. Mutation analyses of overt-FL by targeted next-generation sequencing identified multiple potential pathogenic changes involving CREBBP, EZH2, KMT2D, TNFRS14, and STAT6. Further investigations of these mutations in paired ISFNs using Fluidigm PCR and Illumina sequencing showed the presence of the FL-associated mutations in early lesions for two of the six cases investigated (CREBBP and KMT2D in one case and STAT6 in the other), with one case displaying stepwise accumulation of its observed mutations. Remarkably, there were considerable divergences in BCL2 variants among different ISFN-involved lymph nodes in all four cases successfully investigated, indicating ongoing intraclonal diversification by somatic hypermutation machinery. Our findings demonstrate widespread distribution of ISFN lesions, further implicating their dynamic nature with the neoplastic cells undergoing active trafficking and clonal evolution. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
| S-EPMC9310836 | biostudies-literature
Project description: Not available
| S-EPMC6302496 | biostudies-literature
Project description:ObjectivesCardiac output (CO) response to dobutamine can identify Alagille's syndrome (ALGS) patients at higher risk of cardiovascular complications during liver transplantation. We propose a novel patient-specific computational methodology to estimate the coronary autoregulatory responses during different hemodynamic conditions, including those experienced in a post-reperfusion syndrome (PRS), to aid cardiac risk-assessment.Material and methodsData (pressure, flow, strain and ventricular volumes) from a 6-year-old ALGS patient undergoing catheter/dobutamine stress MRI (DSMRI) were used to parameterize a closed-loop coupled-multidomain (3D-0D) approach consisting of image-derived vascular models of pulmonary and systemic circulations and a series of 0D-lumped parameter networks (LPN) of the heart chambers and the distal arterial and venous circulations. A coronary microcirculation control model (CMCM) was designed to adjust the coronary resistance to match coronary blood flow (and thus oxygen delivery) with MVO2 requirements during Rest, Stress and a virtual PRS condition.ResultsIn all three simulated conditions, diastolic dominated right coronary artery (RCA) flow was observed, due to high right ventricle (RV) afterload. Despite a measured 45% increase in CO, impaired coronary flow reserve (CFR) (~1.4) at Stress was estimated by the CMCM. During modeled PRS, a marked vasodilatory response was insufficient to match RV myocardial oxygen requirements. Such exhaustion of the RCA autoregulatory response was not anticipated by the DSMRI study.ConclusionImpaired CFR undetected by DSMRI resulted in predicted myocardial ischemia in a computational model of PRS. This computational framework may identify ALGS patients at higher risk of complications during liver transplantation due to impaired coronary microvascular responses.
| S-EPMC6224049 | biostudies-literature
Project description:Oral disease is linked with systemic inflammation and various systemic conditions, including chronic liver disease. Liver transplantation (LT) candidates often need dental infection focus eradication, and after LT, there is high risk of many inflammation-related complications. We studied whether pre-LT dental status is associated with the occurrence of post-LT complications. This study included 225 adult LT recipients whose teeth were examined and treated before LT, and 40 adult LT recipients who did not have pre-LT dental data available. Data on post-LT complications were collected from the national liver transplant registry and followed up until the end of July 2020. Worse pre-LT dental status was associated with a higher risk of acute rejection post-LT compared to patients with good dental status. Worse dental status was also associated with higher 1-year-post-LT ALT levels and lower albumin levels. In conclusion, poor pre-LT oral health seems to associate with an increased risk of post-LT acute rejection and with elevated ALT levels and decreased albumin levels, suggesting an effect on post-LT liver health. Therefore, prevention and treatment of oral and dental diseases should be promoted early in the course of liver disease.
| S-EPMC10520246 | biostudies-literature
Project description:The burden of chronic kidney disease (CKD) is rising among patients with cirrhosis, though it is not known what impact this has had on outcomes after liver transplantation (LT). All patients listed for LT in the United States between 2002 and 2017 were analyzed, excluding those listed with Model for End-Stage Liver Disease (MELD) exceptions. The primary outcome was post-LT mortality. We defined pre-LT CKD as an estimated glomerular filtration rate <60 mL/minute for 90 days or ≥42 days of hemodialysis. Cox regression determined the association between pre-LT CKD and post-LT mortality. Of 78,640 LT candidates, the proportion with CKD among LT recipients increased from 7.8% in 2002 to 14.6% in 2017 (test for trend, P < 0.001). Among the 39,719 LT recipients, pre-LT CKD was significantly associated with post-LT mortality (hazard ratio [HR], 1.16; P < 0.001) even after adjusting for donor risk index (DRI), age, MELD, etiology, hepatic encephalopathy, simultaneous liver-kidney transplantation (SLKT), and diabetes. There was no mediating influence of SLKT on the effect of pre-LT CKD on post-LT survival (P > 0.05). Therefore, pre-LT CKD has a deleterious impact on post-LT outcomes, which is an impact that is not mediated through SLKT. These findings highlight the need for the identification of CKD when preventative measures are possible.
| S-EPMC8056970 | biostudies-literature
Project description:BackgroundIn nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.MethodsUsing the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.ResultsAmong 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.ConclusionRisk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
| S-EPMC4672637 | biostudies-literature
Project description:Background and objectivesHispanics are the fastest growing population in the USA, and our objective was to determine their waitlist mortality rates, liver transplantation (LT) rates and post-LT outcomes.MethodsAll adults listed for LT with the UNOS from 2002 to 2018 were included. Competing risk analysis was performed to assess the association between ethnic group with waitlist removal due to death/deterioration and transplantation. For sensitivity analysis, Hispanics were matched 1:1 to Non-Hispanics using propensity scores, and outcomes of interest were compared in matched cohort.ResultsDuring this period, total of 154,818 patients who listed for liver transplant were involved in this study, of them 23,223 (15%) were Hispanics, 109,653 (71%) were Whites, 13,020 (8%) were Blacks, 6,980 (5%) were Asians and 1,942 (1%) were others. After adjusting for differences in clinical characteristics, compared to Whites, Hispanics had higher waitlist removal due to death or deterioration (adjusted cause-specific Hazard Ratio: 1.034, p = 0.01) and lower transplantation rates (adjusted cause-specific Hazard Ratio: 0.90, p<0.001). If Hispanics received liver transplant, they had better patient and graft survival than Non-Hispanics (p<0.001). Compared to Whites, adjusted hazard ratio for Hispanics were 0.88 (95% CI 0.84, 0.92, p<0.001) for patient survival and 0.90 (95% CI 0.86, 0.94, p<0.001) for graft survival. Our analysis in matched cohort showed the consistent results.ConclusionsThis study showed that Hispanics had higher probability to be removed from the waitlist due to death, and lower probability to be transplanted, however they had better post-LT outcomes when compared to whites.
| S-EPMC7774861 | biostudies-literature
Project description:Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.
| S-EPMC5480878 | biostudies-literature
Project description:In this study we focussed on malignant post-transplant lymphomas. Post-transplant lymphoma is strongly associated with Epstein-Barr Virus (EBV) infection in contrast to lymphoma arising in an immunocompetent population. Nevertheless, about 1 in 3 PTLD cases are negative for EBV. We used a microarray to define the gene expression profile of different PTLDs to elucidate the pathogenesis of EBV(+) and EBV(-) PTLD and to define whether EBV(-) PTLD is biologically different from EBV(-) lymphoma arising in an immunocompetent host.
2012-06-23 | GSE38885 | GEO
Project description:In this study we focussed on malignant post-transplant lymphomas. Post-transplant lymphoma is strongly associated with Epstein-Barr Virus (EBV) infection in contrast to lymphoma arising in an immunocompetent population. Nevertheless, about 1 in 3 PTLD cases are negative for EBV. We used a microarray to define the gene expression profile of different PTLDs to elucidate the pathogenesis of EBV(+) and EBV(-) PTLD and to define whether EBV(-) PTLD is biologically different from EBV(-) lymphoma arising in an immunocompetent host. PTLD patient samples were randomly selected for RNA extraction and hybridization on an Affymetrix platform. The post-transplant tumors consisted of homogenous sheets of neoplastic cells ensuring reliability of the gene expression data.
2012-06-22 | E-GEOD-38885 | biostudies-arrayexpress