Mitotane-Induced Hyperlipidemia: A Retrospective Cohort Study

Limited data are available about mitotane-nduced hyperlipidemia. We retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma (ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL-c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively. HDL-c, LDL-c, and triglyceride concentrations significantly increased with mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL (P<0.001), a mean LDL peak of 160.1 mg/dL (P<0.001), and a mean triglyceride peak (Tg-P) of 216.7 mg/dL (P=0.042). HDL-P positively correlated with mitotane concentration (r=0.52,P<0.001), while LDL-P levels and Tg-P did not. Gender, body mass index, cortisol overproduction, baseline levels of HDL-c, and triglyceride did not predict change in HDL-c. Similar changes were noticed in subgroup analysis after excluding patients who were using lipid-lowering agents. In conclusion, in ACC patients, mitotane caused significant increases in HDL-c that may counteract the deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs

Distant Metastases From Childhood Differentiated Thyroid Carcinoma:Clinical Course and Mutational Landscape

Context: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. Objective: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. Methods: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age Results: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Conclusion: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC

Mitotane-Induced Hyperlipidemia: A Retrospective Cohort Study

Limited data are available about mitotane-nduced hyperlipidemia. We retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma (ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL-c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively. HDL-c, LDL-c, and triglyceride concentrations significantly increased with mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL ( &lt; 0.001), a mean LDL peak of 160.1 mg/dL ( &lt; 0.001), and a mean triglyceride peak (Tg-P) of 216.7 mg/dL ( = 0.042). HDL-P positively correlated with mitotane concentration ( = 0.52, &lt; 0.001), while LDL-P levels and Tg-P did not. Gender, body mass index, cortisol overproduction, baseline levels of HDL-c, and triglyceride did not predict change in HDL-c. Similar changes were noticed in subgroup analysis after excluding patients who were using lipid-lowering agents. In conclusion, in ACC patients, mitotane caused significant increases in HDL-c that may counteract the deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs

Bone mineral density in young adult survivors of acute lymphoblastic leukemia

BACKGROUND. The purpose of the current study was to determine the prevalence of low bone mineral density (BMD) (ie, osteopenia) and identify factors associated with low BMD in young adult survivors of childhood acute lymphoblastic leukemia (ALL). METHODS. Dual energy x-ray absorptiometry was used to evaluate BMD in 74 randomly selected, long-term childhood ALL survivors initially treated in Minneapolis/St. Paul, Minnesota. Growth hormone (GH)-releasing hormone–arginine stimulation testing was conducted to evaluate peak GH level, and insulin-like growth factor I (IGF-I) and other markers of endocrine functioning were also evaluated in relation to BMD. RESULTS. The mean age at the time of interview was 30 years, and the mean time since diagnosis was 24 years. Low BMD (Z-score, ≤−1) was present in 24% of subjects, including 1 with osteoporosis. Low BMD was substantially more prevalent in men than in women and was strongly associated with short height. The mean height Z-score for those with low BMD was −1.44, compared with a height Z-score of −0.39 ( P < .01) for those with normal BMD. GH insufficiency, low IGF-I Z-score, and current smoking were also suggestive risk factors for low BMD. CONCLUSIONS. In this long-term follow-up study of childhood ALL survivors, low BMD was found to be more prevalent than expected based on population normative data, specifically in men. The health consequences of early-onset BMD problems in childhood ALL survivors need to be carefully monitored. Cancer 2008. © 2008 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61319/1/23912_ftp.pd

Health profiles of 996 melanoma survivors: the M. D. Anderson experience

BACKGROUND: The incidence and survival of melanoma are increasing, but little is known about its long-term health effects in adult survivors. METHODS: A health survey was available from 996 melanoma survivors (577 treated with surgery alone, and 391 with combined treatments). Their medical/physiologic and psychosocial responses were analyzed and compared with those of the survivors from other cancers. RESULTS: The melanoma survivors were 44.8 ± 12.8 years of age at diagnosis (significantly younger than the survivors of other cancers) and 63.7 ± 12.8 years at survey. Melanoma survivors were less likely to report that cancer had affected their health than survivors of other cancers (15.8% vs. 34.9%). The 577 individuals treated with surgery alone reported arthritis/osteoporosis, cataracts, and heart problems most frequently (less often than survivors of other cancers). The 391 individuals who had undergone combined treatments reported circulation problems and kidney problems generally as often as survivors of other cancers. Health problems were not associated with number of decades since diagnosis but with age at diagnosis, treatment modality, and family relationships. CONCLUSION: We present information from a large cohort of long-term survivors of melanoma. As a group, they were less likely to report that cancer had affected their overall health than survivors of other cancers; a number of disease related and psychosocial factors appear to influence their health profiles

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial.</p> <p>Methods</p> <p>We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients.</p> <p>Results</p> <p>Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients.</p> <p>Conclusion</p> <p>Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.</p

Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT–PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time–PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases