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Introduction: Paraneoplastic hypercalcemia is a life-threatening complication and is usually caused by tumoral secretion of parathyroid hormone-related peptide (PTHrP). Endocrinopathies are common adverse events of immune checkpoint inhibitor (ICI) therapy, but only few reports describe ICI-induced hypercalcemia. Case description: We report the case of a 56-year-old patient with penile cutaneous squamous cell carcinoma (cuSCC) who experienced progression after adjuvant radiochemotherapy. Within the AliCe trial, a multicenter, single-arm phase-II study for stage III/IV non-resectable/metastatic cuSCC, he received avelumab (anti-programmed cell death-ligand 1 antibody) in combination with cetuximab (anti-epidermal growth factor receptor antibody). Two hours after the initial treatment, the patient developed severe delirium, initially unresponsive to symptomatic treatment. Paraneoplastic hypercalcemia was diagnosed on the basis of decreased parathyroid hormone, normal calcitriol, and elevated PTHrP levels. Although ICI-related hypercalcemia could not be fully ruled out, study treatment was continued without further neurological symptoms, but had to be discontinued due to disease progression. The patient showed a good response to palliative chemotherapy lasting 10 months before he died due to progressive disease. Conclusion: This case demonstrates the potential risk of severe hypercalcemia. While hypercalcemia of malignancy is associated with an unfavorable prognosis, immune-mediated hypercalcemia should be considered in patients receiving ICI.

Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid (ZA) in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which ZA was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of ZA, the second case experienced hypocalcemia requiring calcium treatment after ZA infusion. Our report shows that ZA may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of ZA in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients.

Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid (ZA) in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which ZA was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of ZA, the second case experienced hypocalcemia requiring calcium treatment after ZA infusion. Our report shows that ZA may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of ZA in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients. [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy (HCM) is a common clinical problem that is associated with considerable morbidity and negative effects on quality of life. Despite the availability of effective medical treatments for HCM, options are needed for cases that are refractory to conventional therapies. In this context, "refractory" refers to reasonable control of calcium in the setting of inpatient hospitalization (after receipt of standard of care therapies, such as continuous intravenous fluids, calcitonin, and intravenous bisphosphonates) with relapse into severe hypercalcemia within days or weeks of discharge from the hospital. Here we discuss drivers of hypercalcemia of malignancy and the physiologic mechanisms whereby they operate to increase serum calcium. Additionally, we discuss multiple available treatments targeted to a given contributory mechanism and also briefly discuss potential future treatments in need of further study. [ABSTRACT FROM AUTHOR]

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Hypercalcemia of malignancy (HCM) is a common clinical problem that is associated with considerable morbidity and negative effects on quality of life. Despite the availability of effective medical treatments for HCM, options are needed for cases that are refractory to conventional therapies. In this context, “refractory” refers to reasonable control of calcium in the setting of inpatient hospitalization (after receipt of standard of care therapies, such as continuous intravenous fluids, calcitonin, and intravenous bisphosphonates) with relapse into severe hypercalcemia within days or weeks of discharge from the hospital. Here we discuss drivers of hypercalcemia of malignancy and the physiologic mechanisms whereby they operate to increase serum calcium. Additionally, we discuss multiple available treatments targeted to a given contributory mechanism and also briefly discuss potential future treatments in need of further study.

Context: Hypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality. Objective: To support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults. Methods: We searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence. Results: We reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low. Conclusion: The evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients' values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations. [ABSTRACT FROM AUTHOR]

Background: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking. Objective: To develop guidelines for the treatment of adults with HCM. Methods: A multidisciplinary panel of clinical experts, together with experts in systematic literature review, identified and prioritized 8 clinical questions related to the treatment of HCM in adult patients. The systematic reviews (SRs) queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. An independent SR was conducted in parallel to assess patients' and physicians' values and preferences, costs, resources needed, acceptability, feasibility, equity, and other domains relevant to the Evidence-to-Decision framework as well as to enable judgements and recommendations. Results: The panel recommends (strong recommendation) in adults with HCM treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP). The following recommendations were based on low certainty of the evidence. The panel suggests (conditional recommendation) (1) in adults with HCM, the use of Dmab rather than an IV BP; (2) in adults with severe HCM, a combination of calcitonin and an IV BP or Dmab therapy as initial treatment; and (3) in adults with refractory/recurrent HCM despite treatment with BP, the use of Dmab. The panel suggests (conditional recommendation) the addition of an IV BP or Dmab in adult patients with hypercalcemia due to tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy but continue to have severe or symptomatic HCM. The panel suggests (conditional recommendation) in adult patients with hypercalcemia due to parathyroid carcinoma, treatment with either a calcimimetic or an antiresorptive (IV BP or Dmab). The panel judges the treatments as probably accessible and feasible for most recommendations but noted variability in costs, resources required, and their impact on equity. Conclusions: The panel's recommendations are based on currently available evidence considering the most important outcomes in HCM to patients and key stakeholders. Treatment of the primary malignancy is instrumental for controlling hypercalcemia and preventing its recurrence. The recommendations provide a framework for the medical management of adults with HCM and incorporate important decisional and contextual factors. The guidelines underscore current knowledge gaps that can be used to establish future research agendas. [ABSTRACT FROM AUTHOR]

Purpose This article aims to increase awareness of, outline pathophysiology for, and offer guidance on supportive care strategies for specific endocrine, neurological, and immunological syndromes associated with paraneoplastic syndromes (PNSs). Summary PNS refers to remote effects that cannot be attributed to the direct or invasive effects of a malignancy. These syndromes are considered clinically important because they may provide early recognition, diagnosis, and management of the malignancy in a timely manner. Many of their presenting symptoms such as ectopic Cushing's syndrome, hypercalcemia of malignancy (HCM), syndrome of inappropriate secretion of antidiuretic hormone (SIADH), neurological dysfunctions, and paraneoplastic autoimmune thrombocytopenia overlap with those of nonneoplastic disorders, yet their pathogenesis and responses to treatments differ. Management of ectopic Cushing's syndrome due to a PNS consists of treatment of the underlying malignancy and its comorbidities. Drug therapies may include ketoconazole, mitotane, metyrapone, somatostatin analogs, and dopamine agonists. Hypercalcemia may be classified into cases with parathyroid hormone (PTH)–dependent causes or PTH-independent causes such as HCM, in which osteoclast inhibitors may be deployed. Treatments of PNS-mediated SIADH include treatment of the underlying malignancy and strategies to increase serum sodium levels. Amifampridine is now considered the first-line agent for paraneoplastic Lambert-Eaton myasthenic syndrome, whereas steroids, intravenous immune globulin, thrombopoietin receptor agonists (eg, romiplostim, eltrombopag, and avatrombopag), fostamatinib, and rituximab may find their niche in treatment of PNS-mediated autoimmune thrombocytopenia. Conclusion Supportive care for PNSs lends opportunities to pharmacists to add quality, value, and safety. [ABSTRACT FROM AUTHOR]

Background/objective: To report a rare case of ectopic parathyroid hormone (PTH) secretion from poorly-differentiated adenocarcinoma and the lessons learned in management. Case report: A 54-year-old woman presented with fatigue, hip pain, and confusion. Workup revealed calcium of 16.9 mg/dl (N: 8.5–10.3 mg/dl), PTH of 981 pg/ml (N: 15–65 pg/ml), and parathyroid hormone-related peptide (PTHrP) of 20 pmol/L (N: 14–27 pmol/L). Parathyroid four-dimensional computed tomography was unrevealing. Magnetic resonance cholangiopancreatography demonstrated innumerable hepatic lesions. Biopsy of the liver and pubic ramus revealed poorly differentiated adenocarcinoma of unknown origin with acinar cell differentiation and focal PTH positivity.Initial treatment with intravenous bisphosphonates and cinacalcet showed a poor response. Calcitonin had a short-lived response. Although chemotherapy significantly improved calcium levels, she was unable to tolerate chemotherapy. Despite a rise in PTH from 196 to 674 pg/ml, denosumab improved calcium levels from 13 to 9.7 mg/dl. She expired due to a cardiac arrest. Discussion: PTH secretion from tumors with acinar cell differentiation outside of the pancreas has not been described. Cinacalcet was ineffective and it is doubtful that the malignant cells had calcium-sensing receptors. Calcitonin was effective initially, but she eventually developed tachyphylaxis. Use of denosumab later in the treatment course has resulted in significant improvement in calcium despite worsening PTH levels. Conclusion: Denosumab is effective in the treatment of paraneoplastic PTH-mediated hypercalcemia and should be considered in patients who have resistance to bisphosphonate therapy.

Background: Hypercalcemia of malignancy (HCM), a PTH-independent process, usually occurs in solid tumors, multiple myeloma, and occasionally lymphomas. It generally results from excess secretion of parathyroid hormone related protein (PTHrP) by the tumor, osteolytic metastases, or rarely, tumor production of 1,25-(OH)2 vitamin D. We present an unusual case of HCM in a patient with refractory acute myelogenous leukemia (AML) without a defined mechanism that was resistant to bisphosphonate therapy. Case report: A 49 year-old woman with refractory AML presented acutely with altered mental status, decreased appetite, nausea, and fatigue. She was found to have HCM with a low intact parathyroid hormone (PTH) level. Her PTHrP and 25-(OH) vitamin D levels were normal, and her 1,25-(OH)2 vitamin D level was suppressed. Other labs were unrevealing, and imaging showed no new osseous lesions. Her hypercalcemia was treated with normal saline, intravenous furosemide, calcitonin, and two doses of pamidronate. Her calcium level normalized but then rebounded and remained elevated despite pamidronate therapy. Denosumab was considered, but due to rapid clinical deterioration, the patient's family pursued comfort care. Discussion: AML is an extremely rare cause of HCM. This is the eighth reported case of AML-related HCM since 2000 and the first known case with bisphosphonate resistance. Our patient's HCM was not explained by typical mechanisms. Several case reports have demonstrated that denosumab can successfully treat bisphosphonate resistant HCM and is a potential therapeutic option.

Ectopic parathyroid hormone (PTH) secretion is rare in children with rhabdomyosarcoma, and only a few pediatric cases have been reported to date. Reports of the use of zoledronic acid (ZA) and Denosumab are limited for the treatment of hypercalcemia of malignancy (HCM) in the pediatric population. The aim of presenting this pediatric case of rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH secretion, was to highlight the benefits of ZA as a first-choice bisphosphonate in this situation with Denosumab as an alternative therapy. The patient was diagnosed at 13 years with alveolar rhabdomyosarcoma. Multiple bone metastases first appeared at 15 years, but he remained normocalcemic until 17 years old when serum calcium was 15.1 mg/dL and PTH 249 pg/mL. While serum calcium responded well after ZA and Denosumab cycles, PTH remained elevated, reaching a peak value of 1851 pg/mL during treatment cycles. We report a patient with rhabdomyosarcoma accompanied by HCM, secondary to ectopic PTH, in whom the HCM was successfully managed with ZA and Denosumab. We believe that ZA should be the bisphosphonate of choice in pediatric HCM with rhabdomyosarcoma, while Denosumab may be another option in ZA-refractory cases. [ABSTRACT FROM AUTHOR]

Hypercalcemia is a frequent and often incidental finding in primary care. The most common causes for hypercalcemia are primary hyperparathyroidism and malignancy. Providers should feel confident in progressing through an initial evaluation with appropriate diagnostics, interventions, and suitable and timely specialty referrals. [ABSTRACT FROM AUTHOR]

Introduction: Hypercalcemia of malignancy (HCM) portends a very poor prognosis, and no established guidelines exist regarding its management. Most instances of HCM are due to local osteolysis or secretion of parathyroid hormone related-peptide, while less than 1% of all cases are due to ectopic secretion of parathyroid hormone. Case Report: We present an unusual case of HCM due to proposed cosecretion of both parathyroid hormone and parathyroid hormone-related protein in a 36-year-old man with a poorly differentiated lung adenocarcinoma. The patient’s hypercalcemia was refractory to conventional measures, including intravenous bisphosphonate therapy (zoledronic acid), and was improved with administration of denosumab. Conclusion: This is the youngest and first case of hypercalcemia of malignancy attributed to cosecretion of PTH and PTHrP from an adenocarcinoma. In refractory cases of HCM, denosumab is a potential option when other conventional measures are unsuccessful.

Objective: Hypercalcemia is a common finding in patients who have an underlying malignancy. Only a few cases of hypercalcemia of malignancy have been linked to more than one mechanism of hypercalcemia. Here, we present a patient with liposarcoma and hypercalcemia of malignancy in the setting of simultaneous elevations in parathyroid hormone-related peptide (PTHrP) and 1,25 dihydroxyvitamin D [1,25(OH)2D] levels. Sarcoma-associated hypercalcemia is a rare disorder. Methods: The patient was an 89-year-old woman with sarcoma-associated hypercalcemia. Multiple mechanisms were uncovered, and treatments were adjusted for them. Literature search for hypercalcemia of malignancy with multiple mechanisms was conducted. Results: This is the first report describing dual mechanisms of sarcoma-associated hypercalcemia and only the fifth report on PTHrP and 1,25(OH)2D simultaneously causing hypercalcemia of malignancy. Conclusion: Based on this finding, we recommend measuring the 1,25(OH)2D levels in conjunction with the PTHrP level in patients with malignancy as this would allow for a more proactive approach to the diagnosis and treatment of hypercalcemia of malignancy.

Patients with hematological malignancies, both treated and untreated, or solid tumors undergoing treatment are at risk of life-threatening complications, which may present in the emergency department (ED). Such emergencies are diverse in etiology and often require prompt treatment. Traditional complications, such as febrile neutropenia, have had recent guideline updates, which incorporate new evidence and a new validated risk stratification tool. In addition, newer approaches to treatment, such as chimeric antigen receptor (CAR) T-cell therapy, are becoming more widely available and have unique associated toxicities. This review discusses the management of the following hematological and oncological emergencies likely to be encountered in the ED: febrile neutropenia, CAR T-cell toxicities, differentiation syndrome, tumor lysis syndrome, hypercalcemia of malignancy, and hyponatremia. [ABSTRACT FROM AUTHOR]

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 20 days (2–78 days). Median OS was 35 days (9–58 days) in those who received definite anti-cancer therapy. Four-week mortality rate was estimated as 59.5%, while this increased to 75.7% within 6 weeks 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. [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy associated with lung, gastrointestinal, and hematologic malignancies is well-described in the literature but has rarely been reported with gynecologic cancers. Even among gynecologic malignancies represented in literature with hypercalcemia, there are only a handful from endometrial carcinoma. Here we describe an atypical case of a patient with endometrial carcinoma who presented with symptomatic hypercalcemia. This case report investigates the atypical presentation of an endometrial carcinoma., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Choi et al.)

Hypercalcemia of Malignancy is a complicated condition often linked to parathyroid hormone, parathyroid hormone-related peptide, or bone metastasis. This report presents a unique case of calcitriol-mediated hypercalcemia in an 89-year-old female with primary pancreatic lymphoma, highlighting the rarity and complexity of this presentation. Initially, the patient's condition was thought to be related to sarcoidosis, but the recurrence of hypercalcemia led to the discovery of pancreatic B-cell lymphoma as the underlying cause. It also emphasizes the need to explore new treatment options. Interestingly, it demonstrates the successful use of cinacalcet in treating calcitriol-induced hypercalcemia in malignancies, which could be a potential therapeutic option for such cases. It also serves as a reminder of the critical need for ongoing research and innovative therapeutic strategies to improve outcomes in managing hypercalcemia caused by malignancies. The case underscores the potential complexities of calcitriol-mediated hypercalcemia, especially in uncommon presentations like primary pancreatic lymphoma., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare., (© 2024 Greater Baltimore Medical Center.)

Context Hypercalcemia of malignancy (HCM) has not been studied in a fashion to determine all possible mechanisms of hypercalcemia in any given patient. Objective The 2 objectives were to assess the completeness of evaluation and to determine the distribution of etiologies of HCM in a contemporary cohort of patients. Methods A retrospective analysis was performed of patients with cancer who developed hypercalcemia over 20 years at a single health system. Laboratory data were electronically captured from medical records to identify cases of parathyroid hormone (PTH)-independent hypercalcemia. The records were then manually reviewed to confirm the diagnosis of HCM, document the extent of evaluation, and determine underlying etiology(ies) of HCM in each patient. Results The initial data set included 167 551 adult patients with malignancy, of which 11 589 developed hypercalcemia. Of these, only a quarter (25.4%) had assessment of PTH with a third of the latter (30.9%) indicating PTH-independent hypercalcemia. Of those with PTH-independent hypercalcemia, a third (31.6%) had assessment of PTH-related peptide (PTHrP) and/or 1,25-dihydroxy (1,25-OH) vitamin D and constituted the 153 cases of HCM examined in this study. Eighty-three of these patients had an incomplete evaluation of their HCM. The distribution of etiologies of HCM was therefore determined from the remaining 70 patients who had assessment of all 3 possible etiologies (PTHrP, 1,25-OH vitamin D, and skeletal imaging) and was as follows: PTHrP, 27%; osteolytic metastases, 50%; and 1,25-OH vitamin D, 39%, with combinations of etiologies being common (approximately 20%). Conclusion HCM is incompletely evaluated in many patients. The distribution of etiologies of HCM in this report differs significantly from the previous literature, warranting further study to determine whether its causes have indeed changed over time. [ABSTRACT FROM AUTHOR]

Hypercalcemia is a common electrolyte abnormality in malignancy and is largely caused by activation of parathyroid hormone (PTH) pathways. We report the case of a 76-year-old man with hypercalcemia primarily owing to 1,25-dihydroxyvitamin D3 overproduction from a high-grade fetal lung adenocarcinoma. Histologically, the tumor itself and tumor-adjacent macrophages were positive for the CYP27B1 protein, a key enzyme that generates 1,25-dihydroxyvitamin D3. Suppression was observed in serum PTH and PTH-related hormone levels, suggesting hypercalcemia is independent of the PTH pathway. Serum calcium level returned to normal after surgical resection of the lung cancer, supporting extrarenal overproduction of 1,25-dihydroxyvitamin D3 elicited by the tumors is the cause of hypercalcemia in this patient.

Background: Few studies have been conducted investigating the use of bisphosphonates in hypercalcemia of malignancy (HCM) in the setting of renal dysfunction. Objective: The primary objective was to compare the incidence of acute kidney injury (AKI) within 7 days of receiving pamidronate for the treatment of HCM with pre-existing renal dysfunction versus normal renal function at the time of pamidronate administration. The secondary objectives explored the effects of pamidronate doses and infusion rates on the safety and efficacy in those with pre-existing renal dysfunction for the treatment of HCM. Methods: A retrospective chart review was conducted on patients who received pamidronate for the treatment of HCM at a community teaching hospital in Indianapolis, Indiana, from January 1, 2013, to May 31, 2017. Results: A total of 141 pamidronate administrations were included (116 patients had normal baseline renal function, and 25 patients had pre-existing renal dysfunction before pamidronate administration for the treatment of HCM). Two (8%) patients developed AKI in the pre-existing renal dysfunction group, compared with 4 (3.4%) patients in those without pre-existing renal dysfunction (P =.288). For those with pre-existing renal dysfunction, the incidence of AKI did not differ based on the dosage of pamidronate given (P =.762) or infusion rates (P =.373). Conclusion: Pamidronate appears to have limited impact on renal function at doses up to 90 mg in the setting of pre-existing renal dysfunction for the treatment of HCM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypercalcemia associated with malignancy is a serious complication of a variety of cancers and affects approximately 20% to 30% of patients with cancer. Denosumab is approved by the US Food and Drug Administration for the treatment of hypercalcemia of malignancy that is refractory to bisphosphonate therapy. OBJECTIVE: To analyze the efficacy and safety of single-dose denosumab as the first-line treatment of hypercalcemia associated with malignancy. METHODS: We retrospectively identified patients who received denosumab 120 mg for the first-line treatment of malignancy-related hypercalcemia in the outpatient oncology clinics between April 1, 2014, and September 15, 2017, and had a corrected serum calcium level of >11 mg/dL. The study's primary end point was the rate of serum calcium normalization (ie, calcium level of <10.5 mg/dL) within 8 weeks of denosumab administration. The secondary outcomes included the time to serum calcium normalization, rates of relapse, and adverse events after denosumab administration. RESULTS: Among the 15 patients included in this study, 12 (80%) achieved normalization of correct serum calcium within 8 weeks of single-dose denosumab administration. For patients reaching normalization of corrected serum calcium levels, the normalization occurred within 4 weeks, and only 1 of the responders had a relapse of serum calcium levels within the 8-week period of denosumab administration. The adverse events that occurred during the 8 weeks after denosumab administration included grade 1 or 2 hypocalcemia (47%) and grade 1 hypophosphatemia (20%). None of the patients reported other adverse events associated with denosumab, such as osteonecrosis of the jaw, edema, headache, or nausea. CONCLUSION: Denosumab may be effective as a first-line treatment for hypercalcemia associated with malignancy. Our findings support the use of denosumab as a first-line treatment of hypercalcemia of malignancy. Denosumab can achieve response rates that are comparable to standard treatment with intravenous bisphosphonates. Prospective randomized trials comparing a single dose of denosumab with bisphosphonate therapy are warranted to provide further insight into how best to manage patients with hypercalcemia associated with malignancy. [ABSTRACT FROM AUTHOR]

Humoral hypercalcemia of malignancy is rarely seen in urothelial cancer. In this report, we present a case of an 81-year-old female patient who presented with a markedly elevated calcium level leading to severe altered mental status and was found to have urothelial cancer. To our knowledge, only three cases of urothelial carcinoma with squamous cell differentiation have been reported. [ABSTRACT FROM AUTHOR]

Background: Historically, intravenous (IV) bisphosphonates with calcitonin are the treatment of choice for hypercalcemia of malignancy. However, evidence is lacking. Objective: The objective of this study was to compare the use of bisphosphonate versus bisphosphonate with calcitonin for moderate to severe hypercalcemia of malignancy. Methods: This was a retrospective study evaluating patients who received bisphosphonate and/or calcitonin for treatment of moderate to severe hypercalcemia of malignancy. Patients received usual care plus either (1) bisphosphonate or (2) bisphosphonate with calcitonin. The primary outcome was change in corrected serum calcium concentrations 48 hours after treatment. Secondary outcomes included corrected calcium levels, incidence of normocalcemia and hypocalcemia, time to normocalcemia, hospital length of stay, and cost avoidance. Results: The 48-hour decrease in corrected calcium was less in the bisphosphonate group than in the combination group (2.4 [1.6-3.4] vs 3.9 [3.5-5.3]; P < 0.001). However, initial calcium levels in the combination group were higher than in the bisphosphonate group, and calcium levels at 24, 48, and 72 hours were similar. Secondary outcomes did not differ. Average cost avoidance with bisphosphonate monotherapy was $11 248 per patient and $291 448 per year. Conclusions and Relevance: In the treatment of moderate to severe hypercalcemia of malignancy, IV bisphosphonate in combination with calcitonin resulted in a higher difference in corrected calcium levels at 48 hours compared with bisphosphonate therapy alone. However, corrected calcium levels in the first 72 hours, time to normocalcemia, and clinical outcomes were similar. The addition of calcitonin increases cost without substantial clinical benefit, and providers may consider avoiding calcitonin. [ABSTRACT FROM AUTHOR]

Objective: To describe a novel presentation of paraneoplastic hypercalcemia caused by a canine salivary carcinoma., Animal: A 6-year-old intact male Husky with hypercalcemia and a spontaneous salivary carcinoma, stage III., Clinical Presentation, Progression, and Procedures: The dog presented with polyuria, polydipsia, and hypercalcemia. Physical examination revealed a 37 X 43-mm firm mass in the ventrolateral aspect of the right-hand side of the neck, caudal to the temporomandibular joint. Incisional biopsy was suspicious of metastatic carcinoma to the mandibular lymph node. A full-body CT scan found a large, heterogenous, contrast-enhancing mass on the right ventrolateral neck that appeared to be originating from either the mandibular lymph node or right mandibular salivary gland. Parathyroid hormone-related protein was considered within normal reference intervals, and both parathyroid glands appeared ultrasonographically normal., Treatment and Outcome: The patient was treated with a marginal surgical excision of the mass, without immediate complications. Histopathology confirmed the presence of a salivary carcinoma with narrow margins of excision and invasion of the mandibular lymph node. Twenty-four hours after surgery, ionized calcium returned to normal reference values and clinical signs completely resolved., Clinical Relevance: Hypercalcemia is an urgent pathology with important systemic implications requiring prompt diagnosis and intervention. In this case report, we identify the first salivary carcinoma associated with a paraneoplastic hypercalcemia, including this pathology as a new differential diagnosis. The hypercalcemia resolved with marginal surgical excision, but interestingly the parathyroid hormone-related protein was not overexpressed, meaning that this neoplasia could mediate hypercalcemia by another pathophysiological mechanism.

Thymoma is a tumor rarely reported in dogs and should be differentiated from mediastinal lymphoma. Clinical signs may have a late onset, and thymoma is often diagnosed when symptoms related to the space-occupying effect or paraneoplastic syndromes occur. CT and fine-needle aspirates or core biopsies are helpful in differential diagnosis, but flow cytometry may improve the pre-operative diagnostic ability. Concurrent paraneoplastic syndromes such as myasthenia gravis and hypercalcemia have been reported; however, their role as prognostic factors is not well determined. Surgical excision is the treatment of choice; adjuvant radiotherapy and/or chemotherapy may prolong survival in cases of incomplete excision or when a thymic carcinoma is diagnosed. Local recurrence and metastasis are infrequently reported; therefore, a long survival time is expected if the tumor is completely excised or if adjuvant therapy is undertaken. This article reports the authors’ experience with 28 dogs affected by 18 thymomas and 10 thymic carcinomas. The median overall survival in this series was 1173 days, and the median disease-free interval was 903 days. Dogs with thymic carcinoma had significantly shorter disease-free intervals and shorter, although not statistically significant, survival times. Dogs with Masaoka Stage III tumors had worse outcomes.

This is a case report of a patient who developed severe, irreversible hypocalcemia after receiving one dose of pamidronate 90 mg for hypercalcemia of malignancy. Hypocalcemia is a known risk of bisphosphonate treatments, but the incidence of severe hypocalcemia is rare, and the risk factors are well established. However, in the treatment of hypercalcemia of malignancy, the treatment objective is to reduce the elevated serum calcium level, and the bisphosphonate is usually given as one time dose only. The potential for developing severe hypocalcemia may not be considered a significant concern in this setting compared to the setting of the treatment of bone metastasis, where the baseline serum calcium level is not elevated and the bisphosphonate is administered at a regular interval of every three to four weeks. Furthermore, there is unawareness of prevalence of vitamin D deficiency in cancer patients, especially in those with advanced cancer, which may lead to inadvertent, severe hypocalcemia from bisphosphonate treatment. The objective of this case report is to bring awareness to the risk of severe hypocalcemia in patients with hypercalcemia of malignancy and the high prevalence of unrecognized vitamin D deficiency in cancer patients. [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy (HCM) is present in one-third of cancer patients and is associated with a significant mortality risk of 50% within 1 month of diagnosis. We aimed to study the impact and outcomes of HCM in hospitalized patients with solid cancer. We analyzed data captured in the National Inpatient Sample database of the Agency of Healthcare Research and Quality. The study included all hospitalizations in adult solid cancer patients between January 2012 and September 2015 with hypercalcemia. All encounters associated with HCM were identified using the ICD-9 code (275.42) for hypercalcemia. Encounters with other known causes of hypercalcemia were excluded. The co-primary outcomes were incidence of HCM and inpatient mortality. During the study period, 7,501,209 hospitalizations met our inclusion criteria. Approximately 1.7% (n = 126,875) of these hospitalizations were related to HCM. This corresponds to approximately 1 in 59 solid malignancy associated hospitalizations. The mean age of patients with HCM was 65.7 years; 49% were females; 69% were Caucasians; 73% had metastatic disease and 22% received a palliative care consult. When compared to those without HCM, those hospitalized with HCM had a significantly longer mean hospital length of stay (7.3 days vs. 5.6 days, p < 0.001), higher inpatient mortality (12.3% vs. 5.5%, adjusted OR 1.76 (95% CI 1.69-1.84), p < 0·0001), and a greater likelihood of discharge to other facilities (27.4% vs. 16.2%, p < 0.0001). Although HCM accounts for < 2% of all hospitalizations in patients with solid cancer, those with HCM display higher mortality than those without HCM. [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy affects 2%–2.8% of cancer patients and is associated with an increased risk of mortality and other symptom-related complications. Standard treatment consists of fluid resuscitation, intravenous bisphosphonates, and calcitonin. Little is known, however, about the benefits of treatment of malignant hypercalcemia in patients with late-stage terminal cancer. We present a case of a hospice patient with squamous cell lung cancer brought to our hospital with newly altered mental status who was found to have hypercalcemia of malignancy. Our discussion centers on the diagnostic dilemma of deciding which patients seeking comfort-focused care may benefit from fluid resuscitation for symptoms of hypercalcemia of malignancy while maintaining the unambiguous goal of comfort care. [ABSTRACT FROM AUTHOR]

Hillel Sternlicht,1 Ilya G Glezerman1,2 1Division of Nephrology and Hypertension, Weill Cornell Medical College, 2Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA Abstract: Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient’s symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet. Finally, anti-PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory cancer with survival on the order of months. Keywords: hypercalcemia of malignancy parathyroid hormone, parathyroid hormone-related protein, calcitonin, bisphosphonates, denosumab, cinacalcet

Hypercalcemia is one of the most common paraneoplastic syndromes in hospitalized malignancy patients. The aim of this study was to determine the clinical characteristics and treatment outcome in hypercalcemia of malignancy. This was a study using medical records of patients with malignancy hospitalized in the Departement of Internal Medicine, Dr. Hasan Sadikin Hospital Bandung between December 2008 and March 2011. Statistical analysis was performed by Wilcoxon and Mann-Whitney tests. There were 40 patients with hypercalcemia of malignancy, consisted of 22 hematologic malignancies and 18 solid tumors. Disturbance of consiousness were found in 4, dehydration in 18, constipation in 6, and nausea and vomiting in 6 subjects. In 16 subjects, no symptoms were found. All subjects received rehydration with normal saline. Bisphosphonate was given in 26 subjects. The difference of decreasing ion calcium level, between the groups who were treated with or without bisphosphonate was 0.59 (0.01–1.17) mg/dL, p=0.0001. In conclusion, hematologic and solid tumors are found in about the same proportion in hypercalcemia associated malignancy. Treatment either with or without bisphosphonate shows good results.

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• Hypercalcemia of malignancy (HCM) occurs in 2–30 % of malignancies • Clinical manifestations depend on severity and/or rapidity of the serum calcium rise • Treatment of the primary disease, including surgery, is instrumental in preventing and treating HCM • The guideline recommends the use of intravenous bisphosphonate (IV BP) or denosumab (Dmab) as initial therapy for HCM • A calcimimetic, an IV BP, or Dmab, are suggested as initial therapy for HCM due to parathyroid carcinomas [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy ( HCM) is a serious metabolic complication whose population-based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records ( OSCER) warehouse of electronic health records ( EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were ≥18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [ CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009-2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]-10.2% [2010]), lowest for prostate cancer (1.4% [2012]-2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0-2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five-year study period. [ABSTRACT FROM AUTHOR]

Zoledronic acid (ZA) administration has been associated with electrolyte abnormalities, including hypocalcemia, hypomagnesemia, hypokalemia, and hypophosphatemia. We describe a case of severe, refractory hypophosphatemia in a patient who received ZA for hypercalcemia of malignancy (HCM). Little data are available that describe the incidence or degree of severity of hypophosphatemia that can occur following ZA administration. In addition, no formal recommendations exist to guide monitoring for or management of electrolyte derangements in the setting of bisphosphonate use. Our patient required daily, high-dose phosphorus replacement beginning day 4 following ZA administration. The average daily dose of phosphorus, including both intravenous and enteral administration, was highest in the first 2 weeks after ZA, averaging 77 mmol/d days 4 through 15, and does not include sources of phosphorus from the patient’s nutrition support. Despite this high amount of supplementation, which was well beyond what meets normal daily requirements and the amount expected to treat “usual” hypophosphatemia, the patient did not achieve sustained normal serum phosphorus levels for over 30 days after ZA. ZA is a favorable option for treating HCM because of its longer duration of action, potent serum calcium-lowering effects, and favorable safety profile. The risk of hypophosphatemia with ZA use is reviewed. [ABSTRACT FROM AUTHOR]

Background: Management of hypercalcemia is based on the manifestation of symptoms and serum calcium levels. It is considered an oncological emergency; therefore, management has to be done on an urgent basis., Aim: In the present study, we analyzed the clinicopathological profile, treatment, and outcome of patients with hypercalcemia in solid malignancies at our institute., Methods: We retrospectively analyzed the medical records of patients diagnosed with cancer and admitted to the department of radiation oncology with hypercalcemia. The parameters studied were age, gender, performance status, date of diagnosis, the primary site of cancer, stage, histopathology, time of presentation of hypercalcemia since initial cancer diagnosis, clinical symptoms, parathyroid hormone levels, liver and renal function tests, bone metastases, management, outcome, and present status., Results: In the present study, 47 patients of hypercalcemia from various solid malignancies were admitted during the study period between 1st January 2018 and 30th April 2022. Head and neck cancer (14, 29.7%) was the most common site of the primary malignancy. Twelve patients had incidental hypercalcemia and were asymptomatic. Management of hypercalcemia included intravenous saline hydration, bisphosphonates, and supportive medication. At the time of analysis, 17 patients were lost to follow-up, 23 patients died, and seven were alive and on follow-up. Median survival was 68.0 days (95% CI: 1.7-134.3 days)., Conclusion: Hypercalcemia of malignancy is considered a metabolic oncological emergency and requires urgent and aggressive management. It gets complicated by a deranged kidney function test. Despite available treatment, it portends an abysmal prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gupta et al.)

Hypercalcemia of malignancy is an oncologic emergency due to tumoral factors that stimulate osteoclast-mediated bone resorption. It requires a combination of recommended treatments (i.e., hydration, bisphosphonate and calcitonin), which may be deleterious in patients with compromised cardiac or renal function or may not control serum calcium levels long term. Recurrent or refractory hypercalcemia may preclude the use of chemotherapeutic agents needed to effectively treat the underlying cancer, which is the cause of hypercalcemia. Denosumab, a fully human monoclonal antibody against RANKL, inhibits the maturation, function and survival of osteoclasts. An open-label, single-arm study of denosumab in patients with hypercalcemia of malignancy despite recent bisphosphonate treatment revealed positive results. Thus, the US FDA recently approved denosumab for the indication of hypercalcemia of malignancy, increasing the options available for patients with this debilitating and life-threatening condition. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examines several patients who received denosumab for hypercalcemia of malignancy (HCM) to describe the effects of denosumab on calcium levels. Topics discussed include the baseline demographic and clinical characteristics of the patients, the use of intravenous bisphosphonates as a first-line medication in HCM and trends in individual patient's corrected calcium values from admission.

Hypercalcemia of malignancy is a common finding associated with different types of cancers; however, its association with urothelial carcinoma of the bladder is rare. We report a case of a 69-year-old male with nonmetastatic urothelial carcinoma of the bladder who developed hypercalcemia that failed to respond to medical management, but resolved completely after undergoing resection of the tumor through radical cystectomy.

Hypercalcemia is a common life-threatening complication associated with several malignancies. Parathyroid-related peptide has been shown to cause hypercalcemia in several solid tumors but rarely in penile cancer. We report a case of penile cancer with hypercalcemia causing metastatic visceral calcification in lungs, liver, and stomach detected on bone scan without significant abnormalities on CT scan. [ABSTRACT FROM AUTHOR]

Since its discovery as the principal mediator of humoral hypercalcemia of malignancy, parathyroid hormone-related protein (PTHrP) has emerged as a key player in skeletal complications associated with solid tumor metastasis to bone. In addition to functioning as an endocrine factor, this pleiotropic peptide mediates its actions locally on tumor and stromal cells in paracrine, autocrine, and intracrine fashion when cancer metastasizes to the bone compartment. Multiple splice variants and newly described PTHrP fragments confer diverse functions to PTHrP that extend beyond binding to its common receptor with parathyroid hormone. Here, we summarize the causal role of PTHrP in humoral hypercalcemia of malignancy and its local involvement in the progression of osteolytic and osteoblastic cancer bone metastases. Clinical and preclinical findings describing how PTHrP regulates tumor and stromal cell interactions are summarized, with emphasis on emerging evidence of PTHrP's role in tumorigenesis and cancer cell proliferation. Finally, we examine therapeutic opportunities and limitations to targeting PTHrP directly and indirectly in cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To report the case of a 28-year-old woman who presented with hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH) 24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm x 57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type) pancreatic mass with liver metastases. Investigations and treatment: Hypercalcemia was acutely managed with intravenous fluids, pamidronate and calcitonin. Investigations for multiple endocrine neoplasia type 1 and parathyroid adenoma were initiated. The identified neuroendocrine tumor was treated with cisplatinum/etoposide chemotherapy. Results: The pancreatic mass (56 mm x 49 mm) and metastases decreased in size with chemotherapy and calcium levels normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm x 58 mm. The patient was given a trial of cinacalcet but was unable to tolerate it. Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49 mm x 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34 mmol/L). Conclusion: Ectopic PTH secreting tumors should be considered when there is no parathyroid related cause for an elevated PTH. Recognizing the association between PTH and hypercalcemia of malignancy may lead to an earlier detection of an undiagnosed malignancy. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) is a rare tumour which frequently occurs in the context of the multiple endocrine neoplasia syndromes, where it coexists with other usually benign tumours. The clinical picture varies and distant metastases are frequently present at diagnosis. Calcitonin levels are elevated in the presence of metastatic disease. Two MTC cases are presented, which had elevated postoperative calcitonin levels. Imaging revealed lung lesions which were originally attributed to metastatic disease from the MTC. However, at follow-up, these cases presented unusual features. The rapid increase in the lung lesions and the development of hypercalcaemia in the first patient suggested a second unrelated tumour. Biopsy of the lung lesion was compatible with lung adenocarcinoma. In the second patient, the appearance of a liver mass, although calcitonin levels remained stable, led to biopsy of the lesion: this was negative for calcitonin and compatible with metastatic lung adenocarcinoma. These MTC cases show that further malignancies may coexist with MTC and may obscure the clinical picture and influence the therapeutic decisions, especially in the case of metastatic disease. Features such as unusual imaging characteristics and the development of hypercalcemia, never encountered in MTC outside the MEN2 syndromes, as well as ‘disproportionately’ low calcitonin levels, incompatible with extensive metastatic disease, were the factors that led to further work-up. Both the cases subsequently proved to carry an unsuspected second malignancy. It is crucial to discriminate the metastatic lesion attributed to MTC from another coexisting primary malignancy, because different therapeutic strategies are needed for each setting. [ABSTRACT FROM AUTHOR]

Abstract: A patient with a primary neuroendocrine tumor of the pancreas, presented with severe hypercalcemia. This hypercalcemia of malignancy (HCM) failed to respond to intensive bisphosphonate treatment and needed continuous enhanced diuresis. Only after successful antitumor therapy did the hypercalcemia subside. Hypercalcemia was associated with increased concentrations of plasma PTHrP, calcitonin and 1,25-(OH)2D3. Bone mineral density was markedly increased. We demonstrated the presence of both PTHrP and calcitonin in the tumor at the mRNA and protein level, using RT-PCR, immunohistochemistry and Western blotting. The high levels of plasma PTHrP and the demonstrated predominant renal mechanism in this case of HCM are suspected to be the cause for its refractoriness to bone resorption inhibitors. Our findings furthermore suggest that the tumoral production of calcitonin and PTHrP might have contributed to the increased bone mineral storage of calcium and thus probably attenuated the development of frank hypercalcemia. [Copyright &y& Elsevier]

Background: Metastasic deposits from malignancies frequently lodge in the skeleton, including the jawbones. Method: A review of the literature was performed in order to provide a coherent overview on the pathogenesis of bone metastasis. Results: Bone metastasis follows complex molecular interactions that enable tumor cells to detach from the primary site, invade the extracellular matrix, intravasate, extravasate, and proliferate within bone. They induce local bone changes that could manifest radiologically as either osteolytic or radiodense. In addition to the direct bone changes, malignancies can elaborate mediators that are released in circulation, leading to generalized osteopenia. Conclusions: The spread of malignant neoplasms to bone is not a random process but rather a cascade of specific molecular events orchestrated through complex interactions between neoplastic cells and their environment. [ABSTRACT FROM AUTHOR]

Humoral hypercalcemia of malignancy is rarely seen in urothelial cancer. In this report, we present a case of an 81-year-old female patient who presented with a markedly elevated calcium level leading to severe altered mental status and was found to have urothelial cancer. To our knowledge, only three cases of urothelial carcinoma with squamous cell differentiation have been reported.

Simple Summary: Thymoma is a tumor of the cranial mediastinum rarely reported in dogs and should be differentiated from mediastinal lymphoma. CT and fine-needle aspirates or core biopsies are helpful in differential diagnosis, but flow cytometry may improve the pre-operative diagnostic ability. In thymomas, paraneoplastic syndromes such as myasthenia gravis and hypercalcemia may develop concurrently with the tumor. Their role as prognostic factors is not well determined. Surgical excision is the treatment of choice, but adjuvant radiotherapy and/or chemotherapy may prolong survival in cases of incomplete excision or if a thymic carcinoma is diagnosed. Local recurrence and metastasis are infrequently reported; therefore, a long survival is expected if the tumor is completely excised or if adjuvant therapy is undertaken. This article reports the authors' experience with 28 dogs affected by 18 thymomas and 10 thymic carcinomas surgically treated from January 2000 to August 2021. The median overall survival time of the entire population was 1137 days; the median disease-free time was 903 days. Dogs with thymic carcinomas had significantly shorter disease-free intervals and shorter, although not statistically significant, survival times. Dogs with Masaoka Stage III tumors had worse outcomes. Thymoma is a tumor rarely reported in dogs and should be differentiated from mediastinal lymphoma. Clinical signs may have a late onset, and thymoma is often diagnosed when symptoms related to the space-occupying effect or paraneoplastic syndromes occur. CT and fine-needle aspirates or core biopsies are helpful in differential diagnosis, but flow cytometry may improve the pre-operative diagnostic ability. Concurrent paraneoplastic syndromes such as myasthenia gravis and hypercalcemia have been reported; however, their role as prognostic factors is not well determined. Surgical excision is the treatment of choice; adjuvant radiotherapy and/or chemotherapy may prolong survival in cases of incomplete excision or when a thymic carcinoma is diagnosed. Local recurrence and metastasis are infrequently reported; therefore, a long survival time is expected if the tumor is completely excised or if adjuvant therapy is undertaken. This article reports the authors' experience with 28 dogs affected by 18 thymomas and 10 thymic carcinomas. The median overall survival in this series was 1173 days, and the median disease-free interval was 903 days. Dogs with thymic carcinoma had significantly shorter disease-free intervals and shorter, although not statistically significant, survival times. Dogs with Masaoka Stage III tumors had worse outcomes. [ABSTRACT FROM AUTHOR]

Hypercalcemia (HCM) occurs in 10-15% of all malignancies, predominantly in patients with solid tumors. This metabolic complication leads to significant morbidity and impairment of quality of life. Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid-hormone-related peptide and several cytokines secreted by tumors. The osteoclast plays a central role as the final common pathway through which these hormones and cytokines act to cause bone lysis. These findings have led to the development of new treatment strategies. Foremost among these has been the introduction of agents such as the newer bisphosphonates and gallium nitrate, which are potent inhibitors of osteoclast-mediated bone resorption. The clinician can now choose from an array of therapeutic approaches based on a consideration of the mechanisms of action, individual clinical circumstances, efficacy, toxicities and costs of available agents. In addition to their use in the management of HCM, non-toxic drugs that effectively inhibit osteoclast function, such as the bisphosphonates, are playing an emerging role in the palliative treatment of the more common clinical problems of painful lytic bone metastases and osteoporosis. [ABSTRACT FROM AUTHOR]