LETTERS TO THE EDITOR Postoperative Aggravation ofHypercalcemia-Leukocytosis Syndrome in a Case of Squamous Cell Type Cholangio-

It has been reported, mainly in Japan, that hypercalcemia and leukocytosis often coexist in malignancies, especially squamous cell carcinomas (1-4). Sato and his colleagues reported that squamous cell carcinoma with hypercalcemia and leukocytosis was successfully transplanted into nude mice, which caused granulocytosis and hypercalcemia and showed both boneresorbing and colony-stimulating activities in vitro (2, 3). They proposed that hypercalcemia and leukocytosis constitute a newparaneoplastic syndrome(2, 3). Weformerly demonstrated with immunohistochemistry that each component of this syndrome, ie hypercalcemia and leukocytosis, was attributable to parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF), respectively, in a case of thyroid anaplastic carcinoma (5) and in four cases of lung cancer (6). Here we report a case ofsquamous cell type cholangiocarcinomawith hypercalcemia-leukocytosis syndrome,which wasaggravated after the surgery. The case is a 69-year-old man presenting with fever and body weight loss. The imaging studies revealed a single large tumor with multiple small lesions of the liver, and the patient was admitted to the department of surgery on June 20, 1996. The laboratory examination showed leukocytosis (white blood cell count: 1 3,700/}il) and normocalcemia ( 10. 1 mg/dl). Serum intactPTHrP and GCSF levels were examined, both of which were high (intact PTHrP 4.4 pg/ml; G-CSF82.5 pg/ml). The resection of the main tumor with radical hepatectomy was performed under the tentative diagnosis of hepatocellular carcinoma on July 22, 1 996, whereas multiple intrahepatic metastatic lesions were left intact. The pathological diagnosis of the resected tumor was squamouscell type cholangiocarcinoma. Postoperatively after the transient decrease in both serum calcium and leukocyte number, the patient developed marked hypercalcemia (14.7 mg/dl) with concomitant worsening of leukocytosis up to 43,800/|il in two weeks after the operation. Serum PTHrP was increased to 12.0 pg/ml. The immunohistochemical study of the resected tumor indicated positive staining of both PTHrP and G-CSF. Although hypercalcemia was successfully treated with pamidronate, leukocytosis continued to increase. The patient died on August 28. An autopsy was not permitted. The present case showed hypercalcemia-leukocytosis syndrome, which was markedly aggravated after the operation despite the evident mass reduction of the tumor. The immunohistochemistry demonstrated that hypercalcemia and leukocytosis were, at least partly, due to PTHrPand G-CSFsecretion by the tumor, respectively, as previously reported (5, 6). It is to be noted that