title: Hypercalcemia-leukocytosis syndrome associated with lung cancer.
abstract: 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.
authors.affiliation: Department of Medicine (II), Okayama University Medical School, Okayama, Japan. a-hiraki@za2.so-net.ne.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.forename: Akihiro
authors.initials: A
authors.lastname: Bessho
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Kenji
authors.initials: K
authors.lastname: Eguchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000401:mortality; D007564:Japan / Q000453:epidemiology; D007964:Leukocytosis / Q000209:etiology* / Q000401:mortality; D008175:Lung Neoplasms / Q000097:blood / Q000150:complications* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000209:etiology*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013577:Syndrome
chemical_list: D002118:Calcium