Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.

An increasing number of long-term surviving bone marrow transplant (BMT) recipients have recovered from their primary disease but are at risk of developing failure of endocrine organs. We investigated 147 patients who underwent allogeneic BMT. Thyroid function was evaluated by serial measurement of basal TSH and free T4 levels as well as by TRH provocative test. Thyroid ultrasound examination was performed for evaluation of thyroid tumor after BMT. Five patients were found to have overt thyroid dysfunction (hypothyroidism in four patients and hyperthyroidism in one patient). Twenty-three patients in the under 9-yr-old group at BMT and 16 patients in the over 10-yr-old group at BMT had subclinical compensated hypothyroidism. Younger age at BMT was the strongest factor for developing thyroid dysfunction, compared with older age (P < 0.001). Only in patients with subclinical compensated hypothyroidism did median basal and peak TSH increase to the upper half of the normal range by 8 yr after BMT and then returned slightly to the middle of the normal range spontaneously. These results suggest that thyroid dysfunction in long-term BMT survivors depends on age at BMT, with a greater risk among younger patients, indicating the need for life-long surveillance.

Background— The peroxisome proliferator–activated receptor-α (PPARα) plays important roles in lipid metabolism, inflammation, and atherosclerosis. PPARα ligands have been shown to reduce cardiovascular events in high-risk subjects. PPARα expression by arterial cells, including macrophages, may exert local antiatherogenic effects independent of plasma lipid changes. Methods and Results— To examine the contribution of PPARα expression by bone marrow–derived cells in atherosclerosis, male and female low-density lipoprotein receptor–deficient (LDLR −/− ) mice were reconstituted with bone marrow from PPARα −/− or PPARα +/+ mice and challenged with a high-fat diet. Although serum lipids and lipoprotein profiles did not differ between the groups, the size of atherosclerotic lesions in the distal aorta of male and female PPARα −/− →LDLR −/− mice was significantly increased (44% and 46%, respectively) compared with controls. Male PPARα −/− →LDLR −/− mice also had larger (44%) atherosclerotic lesions in the proximal aorta than male PPARα +/+ →LDLR −/− mice. Peritoneal macrophages from PPARα −/− mice had increased uptake of oxidized LDL and decreased cholesterol efflux. PPARα −/− macrophages had lower levels of scavenger receptor B type I and ABCA1 protein expression and an accelerated response of nuclear factor-κB–regulated inflammatory genes. A laser capture microdissection analysis verified suppressed scavenger receptor B type I and increased nuclear factor-κB gene expression levels in vivo in atherosclerotic lesions of PPARα −/− →LDLR −/− mice compared with the lesions of control PPARα +/+ →LDLR −/− mice. Conclusions— These data demonstrate that PPARα expression by macrophages has antiatherogenic effects via modulation of cell cholesterol trafficking and inflammatory activity.

Radiation-induced cavernous hemangioma (RICH) is a late complication of cerebral radiation therapy. Long-term survivors of hematopoietic stem cell transplantation (HSCT) who underwent radiation therapy could be at increased risk for RICH. We investigated records of 68 patients who underwent HSCT during childhood or adolescence and were assessed by magnetic resonance imaging (MRI), including T2*-weighted imaging of the brain, annually for 5 years over a range of 6 to 29 years after HSCT. We developed a scoring and grading system for RICH to monitor the process and the progress of radiologic changes. Among the 68 patients investigated, 28 (41.2%) were diagnosed with CH. All 28 patients had received total body irradiation as a conditioning treatment for HSCT and/or cranial radiation therapy before HSCT as part of the treatment of their primary disease. RICH was diagnosed in none of the patients who did not receive radiation (n = 19), in 46.2% of those who received 6 to 12 Gy (n = 39), and in all of those who received 18 to 36 Gy (n = 10). Total RICH scores were correlated with higher radiation doses. Careful and long-term evaluation with MRI, including T2*-weighted imaging, is necessary for HSCT recipients who received radiation therapy before and/or during HSCT.

Abstract-The concentration of apolipoprotein (apo) AI in the artery wall is thought to enhance cellular cholesterol efflux and protect against atherosclerosis. It has been shown that although macrophages do not make apoAI, they respond to it by increased cholesterol efflux. We hypothesized that macrophage production of apoAI would increase cholesterol efflux and reduce atherogenesis. In this study, we produced mice expressing human apoAI under the control of the macrophage-specific scavenger receptor-A promoter (m-AI). Human apoAI was detectable in the serum HDL fraction of m-AI transgenic mice at concentrations too low to affect serum cholesterol or HDL levels. Immunoblotting showed the presence of human apoAI in transgenic macrophage culture supernatants, mostly as lipoprotein-free protein, with a small component associated with HDL-like particles. Atherosclerosis studies using apoAI (Ϫ/Ϫ) mice transplanted with m-AI bone marrow showed that in the absence of macrophage-derived apoE, local expression of apoAI reduced diet-induced lesions in the proximal aorta. Additionally, m-AI macrophages showed a 40% increase in cholesterol efflux compared with control macrophages. These data support the hypothesis that apoAI production by macrophages in the artery wall is protective against atherosclerosis. This protection is likely mediated by increased cholesterol efflux and decreased foam cell formation in vivo.