Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

articleHereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients. Between 2000 and 2005, we prospectively evaluated the clinical, biological, and hepatic Doppler sonography (DS) characteristics of 102 consecutive HHT patients (mean age, 52.5 years; range, 19-88; 80.4%) with an identified genetic mutation. Patients were segregated into three different severity groups according to DS values. Factors predictive of an abnormal DS, according to predetermined criteria, and of a high cardiac index were identified by logistic and linear regression analysis, respectively. Abnormal liver biology and clinical signs of hepatic involvement were present in 35.3% and 27.5% of cases, respectively. Abnormal DS (defined as at least enlargement of the main hepatic artery) was observed in 56 (54.9%) cases, and direct or indirect signs of significant fistulas were present in 26 (25.5%) cases. Abnormal liver biology and a mutation involving the ACVRL1 gene were predictive of hepatic ultrasound (US) abnormalities. The diameter of the main hepatic artery and the presence of focal nodular hyperplasia (FNH) were predictive of a higher cardiac index. CONCLUSION: This large prospective series of previously nonscreened HHT patients identified a subgroup at risk of liver involvement (patients with abnormal liver biology and ACVRL1 mutations) and a subgroup with a higher cardiac index: future studies will show whether such patients would benefit from systematic DS screening and long-term cardiac surveillance

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

articleHereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients. Between 2000 and 2005, we prospectively evaluated the clinical, biological, and hepatic Doppler sonography (DS) characteristics of 102 consecutive HHT patients (mean age, 52.5 years; range, 19-88; 80.4%) with an identified genetic mutation. Patients were segregated into three different severity groups according to DS values. Factors predictive of an abnormal DS, according to predetermined criteria, and of a high cardiac index were identified by logistic and linear regression analysis, respectively. Abnormal liver biology and clinical signs of hepatic involvement were present in 35.3% and 27.5% of cases, respectively. Abnormal DS (defined as at least enlargement of the main hepatic artery) was observed in 56 (54.9%) cases, and direct or indirect signs of significant fistulas were present in 26 (25.5%) cases. Abnormal liver biology and a mutation involving the ACVRL1 gene were predictive of hepatic ultrasound (US) abnormalities. The diameter of the main hepatic artery and the presence of focal nodular hyperplasia (FNH) were predictive of a higher cardiac index. CONCLUSION: This large prospective series of previously nonscreened HHT patients identified a subgroup at risk of liver involvement (patients with abnormal liver biology and ACVRL1 mutations) and a subgroup with a higher cardiac index: future studies will show whether such patients would benefit from systematic DS screening and long-term cardiac surveillance

The prognostic impact of CD163-positive macrophages in follicular lymphoma: a study from the BC Cancer Agency and the Lymphoma Study Association

PURPOSE: We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in the era of rituximab treatment and maintenance. EXPERIMENTAL DESIGN: We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets. RESULTS: An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort). CONCLUSIONS: CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received