Is surgery necessary for incidentally discovered adrenal masses in children?

Background

There are no guidelines that exist to direct the management of incidental adrenal masses (IAM) in children. The aim of this study was to determine if there is a subset of IAMs that could be safely observed.

Methods

A retrospective analysis was conducted of all adrenal masses that were either resected or biopsied between 1990 and 2002 (n = 91) at the Hospital for Sick Children, Toronto. IAM was defined as a solitary adrenal mass discovered by either physical examination (n = 6; 23.1%) or diagnostic imaging for other indications (n = 20; 76.9%), without metastases or biochemical activity.

Results

Twenty-six (28.6%) IAMs were detected (mean age, 4.6 years [range, antenatal to 17 years]; 11 boys, 15 girls). Pathologic diagnoses included neuroblastoma (n = 7), ganglioneuroma (n = 6), adrenocortical adenoma (n = 4), adrenal cyst/pseudocyst (n = 3), adrenal hemorrhage (n = 3), ganglioneuroblastoma (n = 1), nodular cortical hyperplasia (n = 1), and teratoma (n = 1). Eight masses were malignant (30.8%). Two of the 5 masses discovered on antenatal ultrasound scan were neuroblastoma. In comparing the benign with malignant lesions, there was no significant difference in mean size (4.8 cm v 4.3 cm; P = .57), radiologic characteristics, or mode of presentation. Benign lesions occurred more frequently in older children (mean age, 6.5 years v 1.3 years; P = .03).

Conclusions

Clear guidelines cannot be established to predict benign IAM in children. Given the high proportion of malignant lesions, we recommend that all pediatric IAMs should be resected.     

A phase II study of lapatinib,a dual EGFR and HER-2 tyrosine kinase inhibitor,in patients with castration-resistant prostate cancer

ObjectivesEpidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer.MethodsIn this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes.ResultsTwenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days.ConclusionsLapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.     

Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early‐onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large‐scale brain networks. In the present study, we applied graph‐theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization—an architecture that is simultaneously highly segregated and integrated—the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early‐onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034–4046, 2016. © 2016 Wiley Periodicals, Inc .     

Isometric skeletal muscle force measurement in primary myopathies

Introduction: In myopathy patients, it is useful to measure skeletal muscle forces. Conventional methods require voluntary muscle activation, which can be unreliable. We evaluated a device for nonvoluntary force assessment. Methods: We tested 8 patients (unknown myopathy n = 2, inflammatory myopathy, facioscapulohumeral muscular dystrophy, mitochondrial myopathy, dysferlinopathy, multi‐minicore disease, Becker‐Kiener muscular dystrophy, n = 1 each). Isometric twitch torques of ankle dorsiflexors were measured after fibular nerve stimulation. Results: Six patients had decreased torques vs. 8 controls (men: median Newton‐meter 1.6 vs. 5.7, women: 0.2 vs. 3.9, both P < 0.0001). Values correlated with Manual Muscle Test results (r = 0.73; r² = 0.53; P < 0.0001). In weak dorsiflexors, torque could be measured despite lower signal‐to‐noise ratios. In 2 patients with hypertrophy, we measured increased torques. Conclusions: Nonvoluntary muscle force assessment can be used in patients with myopathies, and values correlate with voluntary forces determined by traditional methods. Muscle Nerve 53 : 913–917, 2016     

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease

Objective: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. Results: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. Conclusions: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.     

A case of "fresh rupture" after open repair of a ruptured Achilles tendon

We present the case of Achilles tendon rupture in a 54-year-old man while rehabilitating after end-to-end open repair of an acute Achilles tendon rupture. Re-rupture after surgical repair of Achilles tendon is well known. The present case, however, is atypical, because the second rupture occurred significantly proximal to the first rupture. To our knowledge, this is the first time this has been described in English language studies. We have termed this incident a fresh rupture. A gastrocnemius turndown flap was used to repair the fresh rupture, which led to a satisfactory recovery. This case report serves to inform surgeons of the existence of this type of Achilles tendon rupture, while considering the possible etiologies and suggesting a technique that has been shown to be successful in the present case.     

Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity

Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.