Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma
A 63-year-old male patient was referred to our hospital for evaluation of an intrahepatic mass discovered during a routine health checkup in August 2010. He had no past medical history. Except for corrected serum calcium level of 12.1 mg/dL (normal range, 8.5 to 10.5 mg/dL), the blood test at initial presentation was not remarkable. His electrocardiogram showed normal sinus rhythm and there were no other hypercalcemia-associated symptoms or signs. An abdominopelvic computed tomography (CT) scan showed a large mass measuring 13 cm in size, suggesting CC with intrahepatic metastases and invasion of the left portal vein and hepatic vein (). Sono-guided liver biopsy was performed and the pathologic diagnosis showed poorly differentiated carcinoma, highly suggestive of CC. Because there was no distant metastasis on the positron emission tomography CT scan, we made a diagnosis of locally advanced intrahepatic CC. Given the tumor's unresectable status and the patient's good performance, we decided to treat him with radiotherapy concurrent with capecitabine 1,000 mg/m2 twice daily on days 1-14 and cisplatin 60 mg/m2 day once every three weeks. The first two cycles of chemotherapy were administered with radiotherapy, a total dose of 45 Gy at the main mass in the liver.\nFollow-up CT scan after concurrent chemoradiotherapy (CCRT) showed marked improvement in the patient's tumor status (). In parallel with the improvement of tumor status, serum calcium level showed a decrease to the normal range (). We continued to administer the same treatment regimen, and the response was maintained for nine months, until May 2011, when a follow-up CT scan showed liver metastasis progression. Carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9) level were elevated to 48.17 U/mL (normal range, 0 to 5 U/mL) and 97.0 ng/mL (normal range, 0 to 37 ng/mL), respectively. At the same time, his corrected serum calcium level increased again to 11.1 mg/dL. The suppressed PTH level (5.1 pg/mL; normal range, 15 to 65 pg/mL) with elevated PTH-rp level (6.7 pmol/L; normal range, 0 to 1.1 pmol/L) confirmed the diagnosis of recurrent HHM. We treated the patient with intravenous hydration and pamidronate. Hypercalcemia was resolved in five days and the patient was performing well without any signs or symptoms related to hypercalcemia, therefore, he was treated with second-line chemotherapy with gemcitabine.\nAfter two cycles of gemcitabine, a follow-up CT scan showed liver mass progression and newly developed hematogenous lung metastasis. The corrected serum calcium level was elevated even higher (11.8 mg/dL). Although hypercalcemia was normalized after medical treatment, his poor performance hindered him from receiving additional chemotherapy. Instead, he was treated with the best supportive care. When he visited the outpatient clinic three weeks later, he was in a state of somnolence and oral intake was not possible due to severe nausea and vomiting. His corrected serumcalcium level rose upto 15.3 mg/dL.\nEventually, the patient died on 10 August 2011, almost one year after initial diagnosis of CC with HHM.