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Journal ArticleDOI

Hypercalcemia and cancer: Differential diagnosis and treatment.

01 Sep 2018-CA: A Cancer Journal for Clinicians (American Cancer Society)-Vol. 68, Iss: 5, pp 377-386
TL;DR: The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.
Abstract: Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone-related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.
Citations
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Journal ArticleDOI
TL;DR: The revised TIGAR-O_V2 system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection.
Abstract: The Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and severe acute pancreatitis and Obstructive (TIGAR-O) Pancreatitis Risk/Etiology Checklist (TIGAR-O_V1) is a broad classification system that lists the major risk factors and etiologies of recurrent acute pancreatitis, chronic pancreatitis, and overlapping pancreatic disorders with or without genetic, immunologic, metabolic, nutritional, neurologic, metaplastic, or other features. New discoveries and progressive concepts since the 2001 TIGAR-O list relevant to understanding and managing complex pancreatic disorders require an update to TIGAR-O_V2 with both a short (S) and long (L) form. The revised system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection. The rationale and key clinical considerations are summarized for each updated classification item. Familiarity with the structured format speeds up the completion process and supports thoroughness and consideration of complex or alternative diagnoses during evaluation and serves as a framework for communication. The structured approach also facilitates the new health information technologies that required high-quality data for accurate precision medicine. A use primer accompanies the TIGAR-O_V2 checklist with rationale and comments for health care workers and industries caring for patients with pancreatic diseases.

59 citations


Cites background from "Hypercalcemia and cancer: Different..."

  • ...If the patient has hypercalcemia of malignancy (33), the tumor type should be recorded in the evaluation, consultation, and/or case report form....

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  • ...Other, NOS category is for identified causes of hypercalcemia such as parathyroid tumors (43), multiple endocrine neoplasia (MEN) type 1 or 2a (33,44), other cancers such as multiple myeloma (33,45), or rare causes of hypercalcemia....

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  • ...Approximately 90% of cases of hypercalcemia are caused by primary hyperparathyroidism (PHPT) or hypercalcemia of malignancy (33), with a small subset associated with genetic disorders, sarcoidosis, chronic kidney disease (CKD), and other factors....

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Journal ArticleDOI
TL;DR: The information on PC is updated by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period, as there are no specific clinical, biochemical, or radiological characteristic of PC.

45 citations

Journal ArticleDOI
TL;DR: Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.
Abstract: Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical mediators of hypercalcemia. Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.

37 citations


Cites background from "Hypercalcemia and cancer: Different..."

  • ...It should be noted that primary hyperparathyroidism and malignancy are the two main causes that comprise nearly 90 % of hypercalcemia cases [5, 56, 57], so a diagnostic approach should first focus on distinguishing between these two entities....

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  • ...In contrast, patients with malignancy associated hypercalcemia often have rapidly increasing calcium concentrations along with a rapid duration of onset and are more likely to be symptomatic [5, 56]....

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  • ...Among patients admitted to the hospital, hypercalcemia due to malignancy is 2–3 times more common than primary hyperparathyroidism while the source of malignancy often becomes evident from the history and physical examination [5, 56]....

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  • ...Among all patients who present to the emergency department with hypercalcemia, the most common causes are malignancy followed by primary hyperparathyroidism [2, 5]....

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  • ...Calcitonin is usually administered at a dose of 4–8 IU/kg subcutaneously every 6–12 h; it begins to exert its effect within 4–6 h up to 72 h and decreases calcium levels by 1–2 mg/dl [5, 53, 62]....

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Journal ArticleDOI
TL;DR: The study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated, and a significant increase in calcium levels is confirmed.
Abstract: Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (P = 0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (P = 0.012). After that, seven patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.

22 citations

Journal ArticleDOI
TL;DR: In this paper, the authors focused on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.
Abstract: Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is also used for the treatment of osteoporosis and other bone diseases. However, bisphosphonate also suffers from serious side effects. Thus, there is a serious need to develop bisphosphonate conjugates with promising therapeutic outcomes for treating metastatic bone cancer and osteoporosis. This review article focuses on the biological outcomes of designed bisphosphonate-based conjugates for the treatment of metastatic bone cancer and osteoporosis.

13 citations

References
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Journal ArticleDOI
TL;DR: Osteoclast apoptosis may be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.
Abstract: Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effect on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.

1,007 citations

Journal ArticleDOI
TL;DR: A 47-year-old woman with a history of breast cancer presents with confusion and dehydration and bone scintigraphy reveals no evidence of skeletal involvement by the tumor.
Abstract: A 47-year-old woman with a history of breast cancer presents with confusion and dehydration. The serum calcium level is 18.0 mg per deciliter. She has postural hypotension and low central venous pressure. The serum phosphorus level is 5.0 mg per deciliter, the blood urea nitrogen level 80 mg per deciliter, the serum creatinine level 2.0 mg per deciliter, and the albumin level 3.3 g per deciliter. Bone scintigraphy reveals no evidence of skeletal involvement by the tumor. How should she be treated?

748 citations

Journal ArticleDOI
TL;DR: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.
Abstract: PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] ≥ 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, re...

704 citations

Journal ArticleDOI
01 Apr 2011-Bone
TL;DR: It is suggested that the key pharmacological differences between denosumab and the bisphosphonates reside in the distribution of the drugs within bone and their effects on precursors and mature osteoclasts, which may explain differences in the degree and rapidity of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions.

577 citations