Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Pelvic radiotherapy for cervical cancer affects importantly the reproducibility of cytological alterations evaluation.

BACKGROUND: to evaluate the intraobserver and interobserver reproducibility of cervical cytopathology according to previous knowledge of whether patients received radiotherapy (RT) treatment or not. METHODS: The study analyzed a sample of 95 cervix cytological slides; 24 with cytological abnormalities (CA) and presence of RT; 21 without CA and presence of RT; 25 without CA and without previous RT; 25 with CA and without previous RT. Two cytopathology (CP) evaluations of the slides were carried out. For the first CP re-evaluation, the cytotechnologist was blinded for the information of previous RT. For the second CP re-evaluation, the cytotechnologist was informed about previous RT. The results were analyzed through inter and intraobserver agreement using the unweighted and weighted kappa. RESULTS: Post radiotherapy effects were identified in 44.4% of cases that undergone previous pelvic RT. The agreement for RT status was 66.32% (unweighted K = 0.31, 95%CI: 0.13; 0.49, moderate agreement). The intraobserver agreement, regarding the cytological diagnoses, regardless of radiotherapy status, was 80.32% (weighted K = 0.52, 95%CI: 0.34; 0.68). In no RT group, the intraobserver agreement was 70% (weighted K = 0.47, 95%CI: 0.27;0.65) and in patients that received RT, the intraobserver agreement was 84.09% (unweighted K = 0.37, 95%CI: 0.01;0.74). The interobserver agreement between cytopathology result (abnormal or normal) in the group with RT, considering normal and abnormal CP diagnosis was 14.0% and 12.5%, respectively. There was no association between the cytological alterations and the median time between the end of RT and the cytological diagnosis. CONCLUSION: This study showed that RT has an important impact in CP diagnosis because the agreement, also in interobserver and intraobserver analysis, had high discrepancy in patients that received RT. Also, demonstrated that it is difficult to recognize the presence of RT in cytological slides when this information is not provided.

GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior.

BACKGROUND: Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors. METHODS: A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays. RESULTS: The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (p=0.004), being the expression of this protein associated with shorter overall and disease-free survival (p=0.004 and p=0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%). CONCLUSION: GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.

The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.

BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.