Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma: A case report and management of neonatal hypercalcemia: Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma.

Congenital mesoblastic nephroma is a rare pediatric renal tumor and has been reported in patients presenting with palpable abdominal mass, arterial hypertension, hematuria, polyuria, or hypercalcemia. Here we present the case of a 1-month-old neonate with suspected parathyroid hormone (PTH)-related peptide (PTH-rp)-mediated severe hypercalcemia revealing congenital mesoblastic nephroma. Preoperatively, hypercalcemia was corrected with hydration, furosemide, pamidronate, and low-calcium infant formula. Unilateral nephrectomy led to the resolution of hypercalcemia, transient hyperparathyroidism, and transient vitamin D and mineral supplementation. We conclude that congenital mesoblastic nephroma can secrete PTH-rp that can cause severe hypercalcemia.

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion.

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.

Application of "omics" sciences to the prediction of bone metastases from breast cancer: State of the art.

Breast cancer (BC) is the most frequent malignancy and the first cause of cancer-related death in women. The majority of patients with advanced BC develop skeletal metastases which may ultimately lead to serious complications, termed skeletal-related events, that often dramatically impact on quality of life and survival. Therefore, the identification of biomarkers able to stratify BC patient risk to develop bone metastases (BM) is fundamental to define personalized diagnostic and therapeutic strategies, possibly at the earliest stages of the disease. In this regard, the advent of "omics" sciences boosted the investigation of several putative biomarkers of BC osteotropism, including deregulated genes, proteins and microRNAs. The present review revisits the current knowledge on BM development in BC and the most recent studies exploring potential BM-predicting biomarkers, based on the application of omics sciences to the study of primary breast malignancies.

Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management.

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

The role of biomarkers in the management of bone-homing malignancies.

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles. In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers.

[Hypercalcemia related to PTH-rP revealing malignant hepatic epithelioid hemangioendothelioma]. / Une hypercalcémie humorale maligne révélant un hémangioendothéliome épithélioïde du foie.

Hypercalcemia caused by tumor production of PTH-rp occurs most often in cases of squamous cell carcinoma of the lung, aerodigestive tract cancer, gynecological cancer and lymphoma. We report an exceptional case of PTH-rp related to a hepatic hemangioendothelioma. A 70 years-old male admitted for deterioration of the general state. The laboratory investigations revealed hypercalcemia, related to tumor production of PTH-rp. Imaging revealed tumoral hepatic lesions. Histopathological study and immunohistochemistry showed diffuse response for CD31 marker, CK20 (+) with CK7 (-) and hepatocyt antigen (-). The diagnosis of PTH-rp related to hepatic hemangioendothelioma was make. The patient died with recurrence of fatal hypercalcemia. Management of patients presenting with humoral hypercalcemia includes a vigorous search for tumor lesions. Elevated PTH-rp can be a bad prognostic factor. In front of tumoral liver lesions, a hepatic epithelioid hemangioendothelioma must be considered. Immunohistochemistry is necessary to make diagnosis.

Tumor neuroendócrino de pâncreas: relato de caso de uma neoplasia rara / Neuroendocrine tumor of the pancreas: a case report of a rare neoplasm

Os tumores neuroendócrinos do pâncreas (TPNs) formam um conjunto heterogêneo e raro de neoplasias. Dentre todos os tumores pancreáticos, os adenocarcinomas são os mais comuns, havendo uma relação aproximada de 125 casos de adenocarcinomas para cada caso de TPN. Correspondem a menos de 5% de todas as neoplasias primárias do pâncreas. Podem ser classificados como neoplasias “funcionais” ou “não-funcionais”, de acordo com a ocorrência ou não de uma síndrome clínica específica e relacionada à hipersecreção hormonal pela massa tumoral. Apesar de serem colocadas em um mesmo grupo, tais neoplasias apresentam um espectro de características e sintomas bem variados, havendo necessidade de subclassificá-las. As categorias que representam os TPNs, de acordo com características clínicas e histopatológicas, são: (1) Insulinomas, (2) Gastrinomas (Síndrome de Zollinger-Ellison), (3) Vipomas (Síndrome de Verner-Morrison), (4) Glucagonomas, (5) Somatostatinomas, (6) Tumores Secretores de ACTH, (7) Tumores Secretores de GH (hormônio do crescimento), (8) Tumores causadores de Síndrome Carcinóide, (9) Tumores causadores de Hipercalcemia e (10) Tumores Neuroendócrinos “Não-funcionais”. O presente estudo se propõe a relatar retrospectivamente dois casos de tumor neuroendócrino do pâncreas com quadro clínico caracteristicamente oligossintomático, porém com evoluções e prognósticos distintos, ressaltando-se os diferentes espectros que a doença pode apresentar (AU)

Hypercalcemia as a Presenting Clinical Manifestation of Adenocarcinoma of the Colon.

Hypercalcemia is rarely associated with colon cancer. It is related to overexpression of parathyroid hormone-related protein (PTH-rp) in malignant cells of the primary colon tumor and metastases. A 44 year old lady presented for evaluation of severe hypercalcemia (15.7 mg/dL) associated with abdominal pain, nausea and constipation. She was diagnosed with metastatic colon cancer involving the liver. Therapy for hypercalcemia consisted of intravenous bisphosphonate and saline hydration. Hypercalcemia remained resistant and refractory to treatment despite resection of the colon tumor. She died soon after admission to hospice. It is proposed that malignant cells of the primary colon tumor and distant metastases, in this patient, were the site of ectopic PTH-rp secretion resulting in hypercalcemia. This case illustrates the significance of recognizing hypercalcemia as a potential clue in detecting underlying colon cancer involving overproduction of PTH-rp. It also exemplifies the poor prognosis expected with this type of humoral hypercalcemia of malignancy and the difficulty encountered when trying to achieve normalization of calcium in this setting.

A Male Patient with Humoral Hypercalcemia of Malignancy (HHM) with Leukocytosis Caused by Cutaneous Squamous Cell Carcinoma Resulting from Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disorder. Although the patients are at risk for cutaneous squamous cell carcinoma (SCC), no case of cutaneous SCC derived from RDEB with humoral hypercalcemia of malignancy (HHM) has been reported. We present the first case report of a male patient with HHM with leukocytosis caused by cutaneous SCC resulting from RDEB. A 20-yr-old Japanese male patient with RDEB; the diagnosis was confirmed by electron microscopic examination, suffered an intractable skin ulcer and hypercalcemia and leukocytosis. PTH-rP, SCC antigen and Granulocyte colony-stimulating factor (G-CSF) levels were elevated. The histological diagnosis of the skin lesion was made well-differentiated SCC. Immunohistochemical staining showed the expression of PTH-rP in atypical tumor cells. For the control of hypercalcemia before an amputation, we used zoledronate safely and could control the serum Ca concentration in the normal range. After the amputation of his right leg including SCC, leukocytosis improved immediately and PTH-rP in blood decreased to the normal range. One month after the amputation, local recurrence of cutaneous SCC and multiple lung metastases were observed. PTH-rP increased gradually associated with hypercalcemia. Although the patient reached an unfortunate turning point about 4 mo after the amputation, we propose that zoledronate is an effective and safe treatment for HHM with cardiorenal complications.

Association between calcium intake, parathormone levels and blood pressure during pregnancy / Asociación entre consumo de calcio, niveles de parathormona y presión arterial en el embarazo

Purpose: To evaluate the association between calcium intake from diet, calciotropic hormones (PTH, PTH-rp), vasoactive regulators (endothelin, nitric oxide) and blood pressure levels during pregnancy, birth and puerperium. Method: In a prospective study 149 healthy normotensive primigravidas were followed-up from 15 weeks of gestation to puerperium. Daily calcium intake, calciuria, PTH, PTH-rp, endothelin, nitrite-nitrate, and Holter Test were assessed. Linear regression models were performed to evaluate the association between calcium intake, blood pressure levels and the laboratory tests. Multivariate regression models were performed to control potential confounders. Results: A significant increase of calcium intake during pregnancy was observed (931±301 mg/day to 1,195±467 mg/day, p<0.001). Plasma PTH-rp, endothelin, and nitrite-nitrate levels did not change during pregnancy. Among the women 38 (25.4%) had low calcium intake (<800 mg/day) with a larger increase of systolic and diastolic blood pressure during pregnancy (p=0.04) birth (p=0.006) and puerperium (p=0.01). After adjusting for other factors the multivariate analyses showed statistical association between low calcium intake, high parathormone levels and high systolic blood pressure levels during pregnancy (p=0.002). Conclusion: Low calcium intake during pregnancy is associated with a larger increase of systolic blood pressure and high parathormone levels.

Objetivo: Evaluar la asociación entre la ingesta de calcio en el embarazo, los niveles de presión arterial, las hormonas calciotrópicas (PTH, PTH-rp) y sustancias vasorreguladoras (endotelina, óxido nítrico). Métodos: Se realizó un estudio prospectivo con 149 primigrávidas normotensas que fueron incluidas en la semana 15 de gestación con seguimiento y evaluación hasta el puerperio. Se evaluó la ingesta diaria de calcio, la monitoría Holter de 24 horas, la calciuria, PTH, PTH-rp, la endotelina, nitritos y nitratos. Se siguieron modelos de regresión lineal para evaluar la asociación entre la ingesta de calcio, la presión arterial, las hormonas calciotrópicas y los vasorreguladores. Para controlar las variables de confusión se hicieron modelos de regresión múltiple. Resultados: Durante el embarazo la ingesta de calcio aumentó significativamente (931±301 mg/día a 1,195±467 mg/día, p<0.001). Entre las embarazadas 38 (25.4%) tuvieron una baja ingesta de calcio (<800 mg/día) asociada con mayores niveles de presión arterial sistólica y diastólica durante el embarazo (p=0.04), en el parto (p=0.006) y en el puerperio (p=0.01). Los mayores niveles de presión arterial sistólica durante el embarazo se asociaron con mayores niveles de paratormona y con menores niveles de ingesta de calcio (p=0.002). Los niveles plasmáticos de PTH-rp, endotelina, nitritos y nitratos no mostraron cambios durante el embarazo. Conclusión: La baja ingesta de calcio en el embarazo se asoció con mayores niveles de paratormona y de presión arterial sistólica durante el embarazo.