Testicular juvenile granulosa cell tumor: a case report.

The Testicular Juvenile Granulosa Cell Tumor (JGCT) is a rare testicular neoplasm that appears in the first months of life as a painless testicular mass. Following an accurate radiological ultrasound diagnosis, through which the cystic appearance of the lesion is observed, and histological confirmation, showing follicular growth pattern and an immunoreactivity for inhibin, the treatment process involves, when feasible, conservative surgery. We present the case of a 2-months old infant with a bilateral JGCT of the testis and we review the classical findings of the patology.

A multicentric study of radiomics and artificial intelligence analysis on contrast-enhanced mammography to identify different histotypes of breast cancer.

OBJECTIVE: To evaluate the performance of radiomic analysis on contrast-enhanced mammography images to identify different histotypes of breast cancer mainly in order to predict grading, to identify hormone receptors, to discriminate human epidermal growth factor receptor 2 (HER2) and to identify luminal histotype of the breast cancer. METHODS: From four Italian centers were recruited 180 malignant lesions and 68 benign lesions. However, only the malignant lesions were considered for the analysis. All patients underwent contrast-enhanced mammography in cranium caudal (CC) and medium lateral oblique (MLO) view. Considering histological findings as the ground truth, four outcomes were considered: (1) G1 + G2 vs. G3; (2) HER2 + vs. HER2 - ; (3) HR + vs. HR - ; and (4) non-luminal vs. luminal A or HR + /HER2- and luminal B or HR + /HER2 + . For multivariate analysis feature selection, balancing techniques and patter recognition approaches were considered. RESULTS: The univariate findings showed that the diagnostic performance is low for each outcome, while the results of the multivariate analysis showed that better performances can be obtained. In the HER2 + detection, the best performance (73% of accuracy and AUC = 0.77) was obtained using a linear regression model (LRM) with 12 features extracted by MLO view. In the HR + detection, the best performance (77% of accuracy and AUC = 0.80) was obtained using a LRM with 14 features extracted by MLO view. In grading classification, the best performance was obtained by a decision tree trained with three predictors extracted by MLO view reaching an accuracy of 82% on validation set. In the luminal versus non-luminal histotype classification, the best performance was obtained by a bagged tree trained with 15 predictors extracted by CC view reaching an accuracy of 94% on validation set. CONCLUSIONS: The results suggest that radiomics analysis can be effectively applied to design a tool to support physician decision making in breast cancer classification. In particular, the classification of luminal versus non-luminal histotypes can be performed with high accuracy.

Radiomics and artificial intelligence analysis by T2-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging to predict Breast Cancer Histological Outcome.

OBJECTIVE: The objective of the study was to evaluate the accuracy of radiomics features obtained by MR images to predict Breast Cancer Histological Outcome. METHODS: A total of 217 patients with malignant lesions were analysed underwent MRI examinations. Considering histological findings as the ground truth, four different types of findings were used in both univariate and multivariate analyses: (1) G1 + G2 vs G3 classification; (2) presence of human epidermal growth factor receptor 2 (HER2 + vs HER2 -); (3) presence of the hormone receptor (HR + vs HR -); and (4) presence of luminal subtypes of breast cancer. RESULTS: The best accuracy for discriminating HER2 + versus HER2 - breast cancers was obtained considering nine predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 88% on validation set). The best accuracy for discriminating HR + versus HR - breast cancers was obtained considering nine predictors by T2-weighted subtraction images and a decision tree (accuracy of 90% on validation set). The best accuracy for discriminating G1 + G2 versus G3 breast cancers was obtained considering 16 predictors by early phase T1-weighted subtraction images in a linear regression model with an accuracy of 75%. The best accuracy for discriminating luminal versus non-luminal breast cancers was obtained considering 27 predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 94% on validation set). CONCLUSIONS: The combination of radiomics analysis and artificial intelligence techniques could be used to support physician decision-making in prediction of Breast Cancer Histological Outcome.

Patients With Brain Metastases Deserve Better-A Hard-Won Perspective.

This Viewpoint advocates for better research in treatments and clinical practice for brain metastasis stemming from lung cancer.

Clinical-radiomic models based on digital breast tomosynthesis images: a preliminary investigation of a predictive tool for cancer diagnosis.

Objective: This study aimed to develop a clinical-radiomic model based on radiomic features extracted from digital breast tomosynthesis (DBT) images and clinical factors that may help to discriminate between benign and malignant breast lesions. Materials and methods: A total of 150 patients were included in this study. DBT images acquired in the setting of a screening protocol were used. Lesions were delineated by two expert radiologists. Malignity was always confirmed by histopathological data. The data were randomly divided into training and validation set with an 80:20 ratio. A total of 58 radiomic features were extracted from each lesion using the LIFEx Software. Three different key methods of feature selection were implemented in Python: (1) K best (KB), (2) sequential (S), and (3) Random Forrest (RF). A model was therefore produced for each subset of seven variables using a machine-learning algorithm, which exploits the RF classification based on the Gini index. Results: All three clinical-radiomic models show significant differences (p < 0.05) between malignant and benign tumors. The area under the curve (AUC) values of the models obtained with three different feature selection methods were 0.72 [0.64,0.80], 0.72 [0.64,0.80] and 0.74 [0.66,0.82] for KB, SFS, and RF, respectively. Conclusion: The clinical-radiomic models developed by using radiomic features from DBT images showed a good discriminating power and hence may help radiologists in breast cancer tumor diagnoses already at the first screening.

Congenital lung malformations: can we avoid computed tomography? A five-year study.

Purpose: Congenital lung malformations (CLMs) consist of a variety of pulmonary development disorders. In the CLM approach, computed tomography (CT) is considered the gold standard imaging technique due to the high-resolution for the lung parenchyma evaluation, the study of the vascular system after contrast injection, and the multiplanar reconstructions. In the paediatric population CT is considered too invasive due to ionizing radiation and the use of contrast agent. Therefore, the indications for the use of magnetic resonance imaging (MRI) are increasing. The aim of our study is to compare retrospectively MRI and CT in the evaluation of CLMs, to reduce or avoid the use of contrast-enhanced CT in the paediatric population. Material and methods: We retrospectively evaluated 22 paediatric patients with prenatal diagnosis of CLMs. All the patients underwent postnatal MRI in the first 2 weeks of life (except for a patient) and pre-surgery contrast-enhanced CT. A total of 7 blinded radiologists divided into 3 different groups independently reviewed each MRI and CT examination. Sensitivity and specificity of radiologists with different years of experience on the field, as well as of MRI findings regarding every pathology, were evaluated using a ROC curve. The interobserver agreement regarding the MRI findings was also measured. Results: Analysing the ROC curves, we observed that MRI provided a satisfactory accuracy for diagnosing most congenital pulmonary diseases. Conclusions: Our study showed that MRI without contrast agent allows us to reach a CLM diagnosis in good agreement with contrast-enhanced CT, which is considered the gold standard imaging technique.

Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance.

Almost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (rg = 0.368, SE = 0.076, P = 1.61 × 10-6), cannabis use disorder (rg = 0.309, SE = 0.033, P = 1.97 × 10-20) and nicotine (rg = 0.117, SE = 0.043, P = 7.0 × 10-3), as well as drinks per week (rg = 0.087, SE = 0.021, P = 6.36 × 10-5), cigarettes per day (rg = 0.11, SE = 0.024, P = 4.93 × 10-6) and life-time cannabis use (rg = 0.234, SE = 0.029, P = 3.74 × 10-15). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP = 0.6, SE = 0.22, P = 1.6 × 10-3). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders (SUDs), we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. The results from this study further supports the existence of underlying shared biology that drives the overlap in substance dependence in schizophrenia, including specific biological systems related to metabolism and neuronal function.

Extensive solitary lymphatic malformation of the liver in a child: a case report and literature review.

Intrabdominal lymphatic malformations are rare benign congenital vascular anomalies that account for less than 5% of benign masses in childhood, with an extremely variable clinical presentation. For this reason, although their radiological appearance is usually typical, diagnosis can be challenging and not always immediate. This report describes a unique case of extensive solitary hepatic lymphatic malformation in a 10-year-old boy with both extra- and intraparenchymal development with no associated symptoms. A literature review of reported cases of solitary hepatic lymphatic malformation is also included.

Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells.

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype-genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD-both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.

Surgical Options and Approaches for Lower Gastrointestinal Bleeding: When do we operate and what do we do?

Lower gastrointestinal bleeding (LGIB) is a common entity encountered by the surgeon. Though most LGIB stops on its own, familiarity with the diagnoses and their treatments is critical to optimal patient care. Even in 2016, surgery may be required. Advances in imaging have led to an enhanced ability to localize bleeding. Newer anticoagulants have developed which provide ease of use to the patient, but challenges to caregivers when bleeding arises.

Lung ultrasound for the diagnosis of pneumonia in children with acute bronchiolitis.

BACKGROUND: Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. METHODS: We enrolled children admitted to our hospital in 2016-2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient's clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. RESULTS: Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen's kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). CONCLUSIONS: This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. TRIAL REGISTRATION: Identifier: NCT03280732 . Registered 12 September 2017 (retrospectively registered).

Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer.

PURPOSE: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. RESULTS: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively involved in the resistance mechanism. CONCLUSION: These results strongly suggest a potential role of these proteins as a new prognostic tool to predict the response to chemoradiation in LARC.

Long-Term Starvation and Posterior Feeding Effects on Biochemical and Physiological Responses of Midgut Gland of Cherax quadricarinatus Juveniles (Parastacidae).

We investigated the effect of long-term starvation and posterior feeding on energetic reserves, oxidative stress, digestive enzymes, and histology of C. quadricarinatus midgut gland. The crayfish (6.27 g) were randomly assigned to one of three feeding protocols: continuous feeding throughout 80 day, continuous starvation until 80 day, and continuous starvation throughout 50 day and then feeding for the following 30 days. Juveniles from each protocol were weighed, and sacrificed at day 15, 30, 50 or 80. The lipids, glycogen, reduced glutathione (GSH), soluble protein, lipid peroxidation (TBARS), protein oxidation (PO), catalase (CAT), lipase and proteinase activities, and histology were measured on midgut gland. Starved crayfish had a lower hepatosomatic index, number of molts, specific growth rate, lipids, glycogen, and GSH levels than fed animals at all assay times. The starvation did not affect the soluble protein, TBARS, PO levels and CAT. In starved juveniles the lipase activity decreased as starvation time increased, whereas proteinase activity decreased only at day 80. The histological analysis of the starved animals showed several signs of structural alterations. After 30 days of feeding, the starved-feeding animals exhibited a striking recovery of hepatosomatic index, number of molts, lipids and glycogen, GSH, lipase activity and midgut gland structure.

Three cases of bone metastases in patients with gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib) are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age), and one man (62 years of age). Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.

Fall-related injuries in a nursing home setting: is polypharmacy a risk factor?

BACKGROUND: Polypharmacy is regarded as an important risk factor for fallingand several studies and meta-analyses have shown an increased fall risk in users of diuretics, type 1a antiarrhythmics, digoxin and psychotropic agents. In particular, recent evidence has shown that fall risk is associated with the use of polypharmacy regimens that include at least one established fall risk-increasing drug, rather than with polypharmacy per se. We studied the role of polypharmacy and the role of well-known fall risk-increasing drugs on the incidence of injurious falls. METHODS: A retrospective observational study was carried out in a population of elderly nursing home residents. An unmatched, post-stratification design for age class, gender and length of stay was adopted. In all, 695 falls were recorded in 293 residents. RESULTS: 221 residents (75.4%) were female and 72 (24.6%) male, and 133 (45.4%) were recurrent fallers. 152 residents sustained no injuries when they fell, whereas injuries were sustained by 141: minor in 95 (67.4%) and major in 46 (32.6%). Only fall dynamics (p = 0.013) and drugs interaction between antiarrhythmic or antiparkinson class and polypharmacy regimen (> or =7 medications) seem to represent a risk association for injuries (p = 0.024; OR = 4.4; CI 95% 1.21 - 15.36). CONCLUSION: This work reinforces the importance of routine medication reviews, especially in residents exposed to polypharmacy regimens that include antiarrhythmics or antiparkinson drugs, in order to reduce the risk of fall-related injuries during nursing home stays.

Structural alterations in the male reproductive system of the freshwater crayfish, Cherax quadricarinatus (Decapoda, Parastacidae).

No diseases affecting reproductive performance have been previously reported in freshwater crayfishes. This study aims to characterise one reproductive system abnormality found in males of Cherax quadricarinatus reared in captivity. Fifteen adult males of C. quadricarinatus (70-110 g) were purchased from San Mateo S.A. farm (Entre Ríos, Argentina) each season during 2007. Macroscopic analysis showed that 26.6% of the animals sacrificed in winter presented brownish distal vasa deferentia. Histological analysis showed different levels of structural abnormality in the epithelium of the vasa deferentia and spermatophore. Granular and hyaline haemocytes were identified within the vasa deferentia but no significant differences were found in the sperm count between normal and brownish vas deferens. Histological analysis of the crayfishes sacrificed in autumn also showed these modifications in 22% of the animals, however, they did not show the brownish colour under macroscopic analysis. The similarities between the male reproductive system syndrome in shrimps and the abnormalities found in C. quadricarinatus are notable. An unspecific response to thermic stress is a possible explanation of these structural alterations.

Diferenciación sexual en la langosta de agua dulce Cherax quadricarinatus (Decapoda: Parastacidae) / Sexual differentiation in the freshwater crayfish Cherax quadricarinatus (Decapoda: Parastacidae)

Determinamos el momento del desarrollo postembrionario en que se produce la diferenciación sexual primaria en la langosta Cherax quadricarinatus. Esta es evidenciada por la presencia de las gónadas y sus respectivos conductos. También determinamos la diferenciación sexual definida por la aparición de los caracteres sexualessecundarios. Se observaron 797 machos, 506 hembras y 456 individuos intersexos de 0.02 a 89.96 g (de criadero y laboratorio). Disecamos una submuestra de 106 machos, 69 hembras y 59 individuos intersexos para la caracterización macroscópica de la estructura gonadal. La diferenciación de los gonoporos se inicia aproximadamente a los 0.10 g, en sincronía con la diferenciación del sistema reproductor en machos, hembras e intersexos. La adquisición de la forma definitiva de ovario, oviducto, testículo y vaso deferente son posteriores. El appendix masculina iniciasu diferenciación a los 0.12-0.2 g y adquiere los rasgos característicos del appendix de los adultos a partir de 1-2 g.La diferenciación de la mancha roja (red patch) ocurre a partir de los 2.3 g.

We determined the earliest stage of postembryonic development at which primary and secondary sexual differentiations occur in the freshwater (“red claw”) crayfish Cherax quadricarinatus. For this purpose,797 males, 506 females and 456 intersex specimens within a weight range of 0.02-89.96 g were observed under stereoscopic microscope to determine the presence of the genital openings at the basis of the third (females) or fifth (males) pair of pereiopods. Animals presenting both pairs of genital openings were considered as intersex. A subsample of 106 males, 69 females and 59 intersex were dissected for the macroscopic characterization of gonad morphology. The development of the genital openings began approximately at 0.10 g, simultaneously with the differentiation of the reproductive system in females, males and intersex. Although the differentiation of the reproductive system started very early in the postembryonic development, the definitive form and colour of ovaries, oviducts, testes and vasa deferentia was acquired later. The differentiation of the appendix masculina began at 0.12-0.2 g and acquired the elongated shape of the adult at 1-2 g. The soft red patch characteristic of adult males started at 2.3 g of body weight in both chelipeds.

Intersex females in the red claw crayfish, Cherax quadricarinatus (Decapoda: Parastacidae)

Cherax quadricarinatus is a large freshwater crayfish species Parastacidae) native of north-west Queensland and the Northern Territory of Australia. The species typically exhibits a gonochoristic sexual system, although in cultured populations various types of intersex individuals have been described as functional males. In the present study, the macroscopic morphology and the gonadal histology of one type of intersex are described and discussed. All intersexes having both pairs of genital openings (female and male openings) and lacking both appendix masculinae and red patches were functional females with normal ovaries and oviducts. From a histological point of view, they did not differ from normal females having previtellogenic and/or vitellogenic ovaries according to size.

Cherax quadricarinatus, es un astácido dulceacuícola de gran tamaño de la (familia Parastacidae) originario delnoroeste de Queensland y del norte de Australia. Presenta un sistema sexual gonocórico, aunque en poblaciones decultivo se han descrito varios tipos de individuos intersexos como machos funcionales. En el presente estudio se describe y discute la morfología macroscópica y la histología gonadal de un tipo de intersexos. Todos los intersexos que presentan ambos pares de aberturas genitales (femeninas y masculinas) y carecen de ambos apéndices masculinos y de la mancha roja, fueron hembras funcionales con ovarios y oviductos normales. Desde el punto de vista histológico no difieren de las hembras normales, presentando ovarios previtelogénicos y/o vitelogénicos de acuerdo a su tamaño.