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 (Fig. 1A). 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.

Follow-up CT scan after concurrent chemoradiotherapy (CCRT) showed marked improvement in the patient's tumor status (Fig. 1B). In parallel with the improvement of tumor status, serum calcium level showed a decrease to the normal range (Fig. 2). 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.

After 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.

Eventually, the patient died on 10 August 2011, almost one year after initial diagnosis of CC with HHM.

A 68-year-old male patient presented with weight loss of 6 kg over two months and abdominal pain for one week. He had no past medical history. Ultrasonography performed at the local hospital showed a mass lesion in the liver, and he was referred to our hospital. An abdominopelvic CT scan showed CC with innumerable liver to liver metastases and node metastases. Sono-guided liver biopsy was performed and the pathologic diagnosis was adenocarcinoma, either primary or metastatic. Because no primary mass was found by esophagogastroduodenoscopy and colonoscopy, we made a diagnosis of CC with liver metastasis and began treatment with palliative chemotherapy, gemcitabine plus cisplatin. His tumor was stable until 28 June 2011, when he visited the outpatient clinic for the eighth cycle of gemcitabine and cisplatin approximately six months after his initial diagnosis.

At that time, his blood test was remarkable for a corrected serum calcium level of 11.8 mg/dL. Otherwise, there were no symptoms or signs related to hypercalcemia and he was in good performance status. After receiving treatment with intravenous hydration and pamidronate, he received the 8th cycle of chemotherapy as scheduled. We scheduled an appointment for another visit to recheck his condition as well as his serum calcium level. When he returned to the outpatient clinic one week later, his mental status was somewhat somnolent. A blood test showed an aggravated corrected serum calcium level of 14.1 mg/dL and decreased liver function; aspartate aminotransferase was three times the normal level (102 IU/mL; normal range, 13 to 34 IU/mL), alkaline phosphatase was 340 U/L (normal range, 38 to 115 U/L), and albumin was decreased to 2.8 mg/dL (normal range, 3.3 to 5.3 mg/dL). Other blood tests were not remarkable. CT scan revealed aggravation of the main mass and a metastatic lesion in the liver, and newly developed ascites. CEA and CA 19-9 levels were elevated to 981.32 ng/mL and 7,450 U/mL, respectively. As the PTH level was suppressed to 4.8 pg/mL and PTH-rP level was increased to 8.3 pmol/L, we were able to make a diagnosis of HHM. He was hospitalized and treated with intravenous hydration and pamidronate. After admission, his hypercalcemia was corrected to a certain degree, but never returned to normal range. Despite improvement in his mental status, his performance status did not recover from Eastern Cooperative Oncology Group 3. Hence we discontinued chemotherapy and treated him with the best supportive care until he expired on 24 July 2011, only approximately one month after diagnosis of HHM.