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PubMed2004

Hypercalcemia-leukocytosis syndrome associated with lung cancer.

Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. Of note, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. However, the relationship between these two paraneoplastic syndromes and clinical outcome is unclear. In the present study, we retrospectively investigated the occurrence of hypercalcemia (> or = 10.2 mg/dl after adjustment for serum albumin concentration), leukocytosis (> or = 14,000/mm3 with no evidence of infection) or both in lung cancer patients (1149 cases). There were 65 cases (5.7%) of hypercalcemia, 16 cases (1.4%) of leukocytosis and six cases (0.5%) of both hypercalcemia and leukocytosis at the time of first presentation. The occurrence of these two distinct paraneoplastic syndromes in the same patients was more frequent than could have been expected by chance alone (P < 0.001). There was a significant correlation between the hypercalcemia-leukocytosis syndrome and performance status (P = 0.002). Survivals of patients with hypercalcemia alone (median survival time: MST 3.8 months, n = 59), leukocytosis alone (MST 1.9 months, n = 10), and the hypercalcemia-leukocytosis syndrome (MST 1.5 months, n = 6) were significantly shorter than those without them (MST 9.5 months, n = 1074; P < 0.001). Moreover, survival of patients with the hypercalcemia-leukocytosis syndrome was significantly shorter than that of patients with hypercalcemia alone (P = 0.013). On the other hand, there was no significant difference in survival between the hypercalcemia-leukocytosis syndrome and leukocytosis alone (P = 0.47). Multivariate analysis of prognostic factors using the Cox proportional hazards model could not demonstrate that the hypercalcemia-leukocytosis syndrome had independent prognostic significance. In conclusion, our results suggest that the hypercalcemia-leukocytosis syndrome is an additional clinical entity of paraneoplastic syndrome and is an indicator for poorer outcome in lung cancer patients, although the frequency of the combined syndrome is very rare (0.5% of cases over a 10 year interval.

Adult↗
PubMed2000

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-1beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor (TGF) alpha, and tumor necrosis factor (TNF) alpha, 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-1beta and TGFalpha 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 TNFalpha 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.

Adult↗
PubMed1997

Hypercalcemia in patients with metastatic renal cell carcinoma: effect of nephrectomy and metabolic evaluation.

PURPOSE: The role of nephrectomy in the management of hypercalcemia in metastatic renal carcinoma is not known. Hypercalcemia in patients with renal cell carcinoma frequently mimics primary hyperparathyroidism and has been attributed to tumor secretion of parathyroid hormone related protein. We determined the role of cytoreductive surgery in patients with metastatic renal cell carcinoma and hypercalcemia, identified factors that predict patient benefit from surgery, and evaluated the mechanisms of hypercalcemia in these patients. MATERIALS AND METHODS: A total of 15 patients with metastatic renal cell carcinoma and hypercalcemia underwent metabolic and laboratory evaluation followed by nephrectomy. Post-operatively they were followed for changes in serum calcium levels. We selected 18 normocalcemic patients with metastatic renal cell carcinoma and 4 normocalcemic patients without renal cancer to serve as control groups for survival and parathyroid hormone related protein expression. RESULTS: A decrease in serum calcium corrected for albumin occurred in 9 of 11 patients at 1 to 4 weeks after nephrectomy and in 7 of 12 patients at 5 to 16 weeks after nephrectomy. Clinical evaluation supported a parathyroid hormone related protein mechanism of hypercalcemia in 5 of 8 patients. Two patients had evidence of local osteolytic hypercalcemia and 1 had prostaglandin mediated hypercalcemia. CONCLUSIONS: Nephrectomy temporarily ameliorated hypercalcemia in a subgroup of patients with metastatic renal cancer and hypercalcemia. Parathyroid hormone related protein expression was commonly found to be associated with hypercalcemia. Nonparathyroid hormone related protein mechanisms of hypercalcemia in renal carcinoma may be more common than previously thought.

Adult↗