Hypercalcemia In Cancer Patients Research Articles

The Rate and Risk Factors of Acute Kidney Injury among Cancer Patients' Admissions in Palestine: A Single-Center Study.

Introduction Acute kidney injury (AKI) remains a critical issue for cancer patients despite recent treatment improvements. This study aimed to assess the incidence of AKI in cancer patients and its related risk factors. Methods A Retrospective cohort study was conducted at tertiary hospitals in the period 2016–2018. A data abstraction sheet was used to collect related variables from patients' records. During admission, the incidence of AKI was assessed using creatinine measurements. RIFLE criteria were used to classify it into five categories of severity: risk, injury, failure, loss, and end-stage renal disease. Results Using RIFLE (Risk, Injury, Failure, Loss, and End-stage renal disease) criteria, 6.9% of admissions were complicated with AKI. The severity of these fell into the categories of risk, injury, and failure, 3.3%, 1.7%, and 1.9%, respectively. In the multivariate model, the odds for developing AKI was significantly higher for patients with congestive heart failure (AOR = 17.1, 95% CI 1.7–80.1), chronic kidney disease (adjusted OR = 6.8, 95% CI 1.4–32.2 (P value 0.017)), sepsis (AOR = 4.4, 95% CI 1.9–10.1), hypercalcemia (AOR = 8.4, 95% CI 1.3–46.1), and admission to the ICU (AOR = 5.8, 95% CI 2.1–16.2). In addition, the mortality rate was nearly seven times higher for patients complicated by AKI (relative risk = 7.6, 95% CI 3.2–18.2). Conclusion AKI was significantly associated with congestive heart failure, chronic kidney disease, sepsis, ICU admission, and hypercalcemia in cancer patients, resulting in poorer outcomes and higher mortality rates. AKI assessment for hospitalized cancer patients should be performed regularly, especially for patients at increased risk.

Hypercalcemia of Malignancy: Time to Pull the Brakes.

Hypercalcemia of malignancy (HOM) is usually seen in advanced stage and carries a poor prognosis. Survival outcomes are dismal and most of the patients are unable to receive subsequent definite anti-cancer therapy. There is lack of any retrospective or prospective data regarding hypercalcemia of malignancy in Indian population. We aim to describe survival outcomes in hypercalcemia associated with solid organ malignancies. Forty-five patients diagnosed with HOM associated with solid organ malignancies were included in the study. Patients were followed up till death. Clinical features and survival outcomes were noted. Squamous cell carcinoma of head and neck region and lung comprised most of the cases associated with HOM. Most of the patients presented with poor performance status. Median overall survival (OS) was 20days (2-78days). Median OS was 35days (9-58days) in those who received definite anti-cancer therapy. Four-week mortality rate was estimated as 59.5%, while this increased to 75.7% within 6weeks from the diagnosis of hypercalcemia. Survival outcomes are poor after the diagnosis of hypercalcemia in cancer patients. Best supportive care including hospice care should be strongly considered at this point of time instead of definite systemic anti-cancer therapy.

Hypocalcemia in cancer patients: An exploratory study.

Introduction:Calcium has several physiological functions and when it registers abnormal serum levels those functions may be impacted with potentially severe consequences. There is much research on hypercalcemia in cancer patients, but there are no recent studies on the prevalence of hypocalcemia in those patients. However, there has been an evolution in oncology, namely, new drugs that may directly or indirectly result in hypocalcemia. The primary aim was to explore the association of hypocalcemia with the diverse types of cancer. The secondary aim was to study the influence that hypocalcemia might have on survival.Methods:Review of the records of patients ≥18 years old, with total calcium <2.0 mmol/L measured in 2013 in a cancer center.Results:Eight hundred twenty-nine patients were included. Four hundred thirty-nine (53%) were male. The median age was 63 years. The most frequent cancer diagnoses were hematological 196 (24%) and colorectal 111 (13%). Six hundred thirty-eight patients had measured serum albumin, with a median of 25.5 g/L (14–47). When corrected for albumin level, calcium was in the normal range in 210 (33%) cases. The median survival of patients with corrected calcium lower than normal was 479 days (95% confidence interval [CI]: 309–649) and that of patients with normal corrected calcium was 62 days (95% CI: 33–91), P < .001. In a multivariate analysis, age, primary cancer, and albumin were significantly associated with survival.Conclusion:Hypocalcemia is associated with several types of cancer. A low calcium level is not by itself a factor of a poor prognosis since other factors seem to be more important.

INTERFERENCE BY FDG RADIONUCLIDE MOLECULES USED FOR PET-CT MONITORING ON 25-HYDROXY VITAMIN D MEASURED BY LC-MS/MS

Ponte Academic JournalJun 2018, Volume 74, Issue 6 INTERFERENCE BY FDG RADIONUCLIDE MOLECULES USED FOR PET-CT MONITORING ON 25-HYDROXY VITAMIN D MEASURED BY LC-MS/MSAuthor(s): Ataman Gonel ,Ismail KoyuncuJ. Ponte - Jun 2018 - Volume 74 - Issue 6 doi: 10.21506/j.ponte.2018.6.8 Abstract:Vitamin D deficiency is a prevalent condition in humans as a result of the inclination to live in indoor settings. Recent advances in laboratory medicine have resulted in replacement of immunoassay methods by LC-MS/MS measurement techniques, which represent the current reference method. However, serum matrix effect resulting in an interference effect may lead to erroneous results in LC-MS/MS. In this study, our aim was to examine the interference of radionuclide molecules used for PET-CT imaging on vitamin D measurements.\\r\\nFor this purpose, 40 ?L of 18F-FDG was added into the control solution consisting of 100 micro-liter (?L) of vitamin D and 25(OH)D measurements were performed at 0 and 60 minutes using LC-MS/MS. Based on the measurements, radioactivity caused by positrons emitted from FDG was found to cause interference on 25(OH)D measurements depending on the elimination half-life. It has been concluded that the interference observed was caused by the radioactivity emitted from radionuclide molecules used in PET-CT imaging rather than the molecular mass of 25(OH)D.\\r\\nIn daily practice, elevated 25(OH)D levels bears clinical significance, particularly with respect to detection of the etiology of hypercalcemia in cancer patients. On the other hand, in patients undergoing PET-CT imaging, interference caused by FDG may lead to overestimation of vitamin D levels, even when measurements with the reference method LC-MS/MS are used; this may direct the clinician away from a diagnosis of bone metastasis. Therefore, detection of hypervitaminosis D after PET-CT imaging should raise a suspicion of interference. Download full text:Check if you have access through your login credentials or your institution Username Password

Bisphosphonate-related osteonecrosis of the jaw: current state of the problem

The article presents review of the literature on the current state of the problem of bisphosphonate-related osteonecrosis of the jaw. In Russia and abroad there are numerous reports of atypical lesions of the maxilla associated with taking medications on the basis of phosphorus or its analogues, in particular bisphosphonates. This is an issue: if earlier bisphosphonate treatment complications were limited to individual clinical observations, currently their frequency, according to different authors, reaches 8-27%. Bisphosphonate-related osteonecrosis of the jaw is characterized by unique etiopathogenic, clinical and diagnostic features that distinguish it from other inflammatory, degenerative and iatrogenic diseases of orofacial region, so it is reasonable to isolate it into an independent nosology, requiring a comprehensive study. According to current data, bisphosphonate-related osteonecrosis of the jaw is a complication of antiresorptive therapy, characterized by necrosis and exposure of bone area, which persists for more than 8 weeks, followed by the process progression in the absence of radiation therapy to the head area in history. Bisphosphonates are antiresorptive agents, potent inhibitors of bone tissue destruction, widely used for the treatment of bone metastasis, multiple myeloma, and hypercalcemia in cancer patients. However, the development of complications such as osteonecrosis of the jaw greatly reduces the positive effects of treatment, and extremely bothersome for patients. Osteonecrosis-related pyo-inflammatory processes of admaxillary tissue, the appearance of persistent sinus tracts on the skin and in the mouth, the risk of pathologic fracture of the jaw impair the quality of life of patients. Presented in the article analysis of currently known data about the bisphosphonate-related osteonecrosis of the jaw should attract the attention of dental surgeons, maxillofacial surgeons, endocrinologists, oncologists to this problem.

Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence

Hypercalcemia is a frequent finding in cancer patients and can be observed in any type of cancer. The physician in charge of cancer patients often ignores non-malignant causes of hypercalcemia. Our objective was to review the causes of hypercalcemia in a large series of cancer patients. We have retrospectively studied in a Cancer Centre all consecutive hypercalcemic (Ca> 10.5 mg/dl) patients over an 8-year period. Of 699 evaluated patients, 642 were analyzed after exclusion of patients whose hypercalcemia resolved after rehydration or who had a normal Ca level after correction for protein concentrations. Clinical information was gathered on the type of cancer, its histology, whether the disease was active or in complete remission, and on the presence of bone metastases. Biochemical data included serum Ca, P(i), proteins in all patients, PTH in most patients, and PTHrP, 25OH-Vitamin D, 1,25(OH)(2)-Vitamin D, TSH, and T4 in selected cases. By order of decreasing frequency, the main causes of hypercalcemia were cancer (69.0 %), primary hyperparathyroidism (24.6 %), hyperthyroidism (2.2 %), milk alkali syndrome (0.9 %), and sarcoidosis (0.45 %). In cancer-related causes, bone metastases accounted for 53.0 % of the cases, humoral hypercalcemia of malignancy (HHM) for 35.3 % while there were 11.7 % of cases apparently due to both HHM and bone metastases. Hypercalcemia was not due to cancer in 97 % (84/87) of the patients who were in complete remission. Even in patients with active neoplastic disease, the number of patients whose hypercalcemia was not due to cancer remained clinically relevant (115/555 = 20.5 %). In the 158 patients with primary hyperparathyroidism, 92 patients were in complete remission and 66 patients had active neoplastic disease. In this large series of hypercalcemia in cancer patients, the cause was not due to cancer in almost one third of the cases. Most patients considered to be in complete remission had hypercalcemia due to a benign condition. In that perspective, serum PTH determination is essential in the approach of hypercalcemic cancer patients since primary hyperparathyroidism is by far the first non-malignant cause of hypercalcemia.

Parathyroid Hormone-Related Protein: An Update

PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes that are part of a larger "PTH gene family." This evolutionary relationship permits them to bind to the same type 1 PTH/PTHrP receptor, which explains why humoral hypercalcemia of malignancy resembles hyperparathyroidism. This review will outline basic facts about PTHrP biology and its normal physiological functions, with an emphasis on new findings of the past 5-10 yr. The medical and research communities first became aware of PTHrP because of its involvement in a common paraneoplastic syndrome. Now, research into the basic biology of PTHrP has suggested previously unrecognized connections to a variety of disease states such as osteoporosis, osteoarthritis, and breast cancer and has highlighted how PTHrP itself might be used in therapy for osteoporosis and diabetes. Therefore, the story of this remarkable protein is a paradigm for translational research, having gone from bedside to bench and now back to bedside.

PTHrP and breast cancer: more than hypercalcemia and bone metastases

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in cancer patients. PTHrP is required for normal breast development and has been shown to promote bone metastases from breast cancers. However, whether the protein also contributes to the formation of primary tumors has been unclear. Two recent papers suggest it may. First, a report in Nature Genetics identified the PTHrP locus as a new breast cancer susceptibility gene. Second, a paper in Journal of Clinical Investigation demonstrated that PTHrP promotes tumor growth and metastases in MMTV-PyMT mice. These studies implicate PTHrP in the development and growth of primary breast tumors and underscore the need for further research.

Zoledronic acid and clodronate in the treatment of malignant bone metastases with hypercalcaemia; efficacy and safety comparative study

The aim of this study is to conduct a comparison study between the efficacy and safety of zoledronic acid and clodronate in malignant hypercalcemia secondary to bone metastases in Egyptian adult patients. This is a prospective observational study conducted 80 patients (40 in each group), who were assigned to receive either zoledronic acid (4 mg over a 30 min infusion) every 3-4 weeks or clodronate (a single dose of 1,500 mg over a 4 h infusion) monthly for 3 months. The primary efficacy analysis was the proportion of patients with at least one skeletal-related event. The safety was assessed based on the frequencies of the reported adverse effects as nausea, vomiting, anemia, etc. The calcium level significantly decreased in both groups. At least one skeletal-related event occurred in 15 (37.5%) patients receiving zoledronic acid and 32 (80%) patients receiving clodronate. Radiotherapy and fractures represented the highest event observed in both groups. At least one adverse event was experienced by 20 (50%) patients treated with zoledronic acid, while 26 (65%) patients on clodronate recorded one or more adverse event. Pyrexia was the most commonly reported side effect and flare phenomena. Both treatment groups were comparable regarding the reported adverse events. Both medications did not show any significant nephrotoxicity detected by elevation in the creatinine level. Zoledronic acid and clodronate have demonstrated clinical utility in the treatment of hypercalcaemia in cancer patients. Zoledronic acid provides a more effective and convenient treatment than clodronate, while both maintaining a similar safety profile.

Hypercalcemia in Cancer Patients: Pathobiology and Management

Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer, occurring in approximately 10-30% of all patients with neoplastic disease, although it occurs much less often in the pediatric setting. Hypercalcemia can emerge in hematologic malignancies, particularly multiple myeloma, as well as assorted solid tumors, primarily lung and breast cancers, and can even dominate the clinical picture in select patients. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, ameliorate the quality of life of these patients, and avoid delays in the implementation of further anticancer treatments. Occasionally, the symptoms of hypercalcemia can appear gradually, and may be non-specific, resembling symptoms of many cancers and other comorbidities, especially in the elderly, thus resulting in an underestimated incidence of hypercalcemia in cancer patients. Of note, there is an increasing number of antineoplastic compounds that can interfere with calcium metabolism. Taking into consideration both the severity of hypercalcemia and the tumor status, health care providers should determine and apply appropriate treatment measures. We provide a comprehensive subjective synthesis of peer-reviewed evidence on the pathophysiology and treatment of hypercalcemia in cancer patients.

Assesment of Intravenous Bisphosphonates Safety from the Spontaneous Reporting System in Taiwan

doubtful). Results: In the past eight years, 20 reports from the database were eligible for this study. The average age of all cases was 65 y/o at the time ADR occurred. It is observed that one female aged 55 with breast cancer experienced avascular necrosis of the femoral heads and resulted in permanent disability. Four male with age of 70 to 88 experienced hypocalcaemia. Among these 4 cases, one male also suffered from acute renal failure, one male developed acute myocardial infarction resulting death, and the other two experienced other electrolytes imbalance. One male aged 66 with chronic renal failure develop acute renal failure after zoledronic acid therapy. Six patients developed haematological and/or infectious associated ADR after the use of intravenous bisphosphonates.[7] Conclusion: These data emphasise that bisphosphonates induced avascular necrosis can not be overlooked. Any unexplained localised pain, numbness and altered sensation should be dealt with caution.[5,6] To prevent severe electrolytes abnormalities and their complications, e.g. neuromuscular, CNS, and cardiac sequelae, monitoring electrolytes panel periodically, supplementing vitamin D and calcium, and correcting any pre-treatment electrolyte abnormalities are essential.[1] Regular monitoring of renal function during intravenous bisphosphonates treatment, with particular attention to patients with pre-existing renal problem, is also suggested.[3] As intravenous bisphosphonates are commonly used to treat hypercalcemia in cancer patients, it is hard to conclude whether the infections and haematological effects are associated with the use of intravenous bisphosphonates directly or with other concomitant chemotherapy. While clinical indications of intravenous bisphosphonates continue to expand, prescribing clinicians should be familiar with their adverse effects profile to ensure the drug safety of intravenous bisphosphonates. References

Relationship of plasma bone cytokines with hypercalcemia in cancer patients

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. This syndrome appears to be a consequence of the tumor production of humoral factors, mainly parathyroid hormone related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy have features suggesting that factors other than PTHrP might play a role in this syndrome. We performed a case-control study in cancer patients with and without hypercalcemia. A total of 105 patients with a variety of tumors, 60 of them with hypercalcemia (corrected serum calcium over 2.6 mmol/l), and 45 without hypercalcemia. In a previous study, we demonstrated that plasma PTHrP was highly associated with hypercalcemia in these patients. In the present study, we measured the plasma levels of various bone cytokines: interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor (TGF) α, and tumor necrosis factor (TNF) α, in these cancer patients. We also determined C-terminal type I procollagen (PICP) and C-terminal telopeptide of type I collagen (ICTP), bone formation and bone resorption markers, respectively, in serum in these patients. We found that these osteolytic cytokines do not increase in plasma by the presence of hypercalcemia. In fact, using a logistic regression analysis, a significant ( P<0.02) association was found between the low plasma levels of IL-1β and TGFα and hypercalcemia, independent of plasma PTHrP and the presence of bone metastasis, in these patients. No significant association between the plasma levels of IL-6 or TNFα and hypercalcemia was found in these cancer patients. Serum ICTP correlated ( r=0.35; P=0.008) with hypercalcemia in these patients, but none of the cytokines studied in plasma correlated with either ICTP or PICP in these hypercalcemic patients. Our data indicate that the circulating levels of several bone cytokines are not enhanced by PTHrP in hypercalcemic cancer patients. The mechanism responsible for the association between the low plasma levels of some of these cytokines and hypercalcemia in these patients remains obscure. However, this finding does not rule out the possible local bone effects of these cytokines, contributing to hypercalcemia in cancer patients.

Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1,25(OH)2D3. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1,25(OH)2D3 with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1,25(OH)2D3 by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1,25(OH)2D3 in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1,25(OH)2D3 in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.

Randomized placebo-controlled trial to assess the efficacy of oral pamidronate on prolonging the time to recurrence of hypercalcemia in cancer patients

Randomized placebo-controlled trial to assess the efficacy of oral pamidronate on prolonging the time to recurrence of hypercalcemia in cancer patients

Clinical manifestations of cancer-related hypercalcemia.

Hypercalcemia is a potentially lethal endocrine disorder occurring in 10% to 20% of cancer patients at some time during the course of their disease. Clinical manifestations vary in severity, depending on the degree and duration of hypercalcemia, rapidity of onset, patient's age, performance status, sites of metastases, previous antineoplastic therapy, and the presence of hepatic or renal dysfunction. The clinical features of hypercalcemia are protean and affect multiple organ systems, resulting most prominently in neurologic, gastrointestinal, renal, cardiovascular, and musculoskeletal morbidity. Recognition of the disorder requires a high index of suspicion because many of its symptoms, such as nausea, anorexia, weakness, fatigue, lethargy, and confusion, are non-specific and, in the patient with a malignancy, can result from other complications of the primary disorder. If identified appropriately as being related to hypercalcemia, such symptomatology is potentially reversible with treatment. Whereas in the ambulatory general medical population the most common cause of hypercalcemia is primary hyperparathyroidism, in cancer patients and hospitalized patients in general, the most common cause is malignancy. Hypercalcemia in cancer patients is, in most cases, due to advanced metastasized disease. Diagnostic tests are useful in the differential diagnosis of hypercalcemia, and such tests, together with an accurate history and careful clinical observation, permit the best therapeutic approach to an individual patient.

A study of prostaglandin E2, parathormone, and response to indomethacin in patients with hypercalcemia of malignancy.

In order to evaluate the relationship of PGE2 to hypercalcemia in cancer patients, 101 patients were screened with a radioimmunoassay for plasma prostaglandin E2 (PGE2) (NL less than 100 pg/ml). Of the 101 patients, 31 were hypercalcemia. Mean PGE2 (+/- SEM) of the 31 patients was 199 +/- 36 pg/ml. Among the 70 normocalcemic patients, mean +/- SEM PGE2 was 85 +/- 12 pg/ml (range = less than 25--225 pg/ml) (P less than 0.001). Seventeen hypercalcemic patients were initially treated with saline and furosemide, then were prospectively screened for serum parathormone (iPTH) and PGE2. Fourteen of 17 patients were then treated empirically with indomethacin (25 mg b.i.d.) for 72 hours and the PGE2 assay was repeated. Prior to therapy with indomethacin (mean +/- SEM), Ca++ = 12.2 +/- 1.5 mg/dl (NL 8.4--10.6 mg/dl), PGE2 = 87.1 +/- 36.8 pg/ml, (range = less than 25--209 pg/ml), and iPTH = 406 +/- 266 pg/ml (NL less than 400 pg/ml) (range = less than 100--825 pg/ml). PGE2 was elevated before treatment in 6/14 patients (breast, colon, renal, lung, neck tumors, and myeloma). Following treatment with indomethacin, PGE2 and calcium fell to normal levels in three patients (breast, colon, renal carcinomas). These results suggest: (1) A bimodal distribution of PGEs exists in hypercalcemic cancer patients. (2). There was some evidence of lack of whole molecule iPTH suppression in these patients. (3) Multiple stimuli of calcium mobilization may play an important etiologic role in a few hyercalcemic cancer patients and may explain the failure of indomethacin to control serum Ca++ in some patients with elevated PGE2.

Prostaglandin-mediated hypercalcemia: A paraneoplastic syndrome

Evidence has been presented for prostaglandin-mediated hypercalcemia and bone resorption in malignancies of both, experimental animals and man. Occurence of hypercalcemia in cancer patients is known for a long time, but its pathogenesis has been poorly understood so far. Besides ectopic parathyroid hormone secretion by tumors, an osteoclast-activating factor released from leukocytes and direct bone destruction by tumor cells, prostaglandins of the E series have to be considered as one of the candicates involved in the pathomechanism of hypercalcemia and osteoclastic osteolysis in cancer patients. This new concept on the pathophysiology of cancer-associated hypercalcemia has implications for the diagnosis and management of this common complication of neoplastic disease.