Case report
An 81-year-old man was referred to our hospital for the treatment of liver cancer. He had chronic liver disease due to significant alcoholic consumption. Enhanced computed tomography (CT) showed a liver tumor with marginal enhancement in the arterial phase at 28 mm in diameter in the right hepatic lobe (Figure 1a).
He underwent right hepatic lobectomy, and the tumor was completely resected. A gross examination showed a firm, solid yellowish white to tan-gray mass (Figure 1b). A histological examination revealed components of both HCC and cholangiocarcinoma. Hematoxylin-eosin staining showed a trabecular-sinusoidal growth pattern, morphologically consistent with HCC (Figure 1c and 1d), and glandular formations pattern, supportive of cholangiocarcinoma (Figure 1c and 1e). Immunohistochemical staining showed that the HCC regions were positive for Hepa-para-1 (Figure 1f), and the cholangiocarcinoma regions were negative for heap-para-1 (Figure 1f), positive for CK 19 (Figure 1g), and positive for CD 56 (Figure 1h). The patient was therefore pathologically diagnosed with CHC.
Both the HCC and cholangiocarcinoma regions were negative for PD-L1 (Figure 1i and 1j). The microsatellite instability status was also negative. The surrounding liver tissue had steatosis with macrovesicular and fibrosis, suggesting alcoholic liver disease.
He underwent adjuvant chemotherapy with TS-1 at 80 mg/day, but CT showed multiple lymph node metastases at 13 months after surgical treatment. He received systemic chemotherapy with gemcitabine and cisplatin (GEM/CDDP), but we had to discontinue the GEM/CDDP therapy due to a severe rash. Because lenvatinib was recommended for first-line HCC treatment at that time, we administered lenvatinib at 8 mg/day for 4 months. However, we ultimately had to discontinue lenvatinib treatment due to grade 3 decreased appetite. Because Atez/Bev became available in Japan after the end of the lenvatinib treatment, we decided to administer combination therapy with Atez/Bev, following institutional review broad approval and the acquisition of written informed consent from the patient.
The laboratory findings before Atez/Bev treatment are shown in Table 1. The platelet count and hepatobiliary enzyme values were within the normal limits. Both hepatitis B surface antigen and hepatitis C virus antibody were negative. The serum levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were also within the normal ranges. Regarding the liver function, the Child-Pugh classification was grade A (5 points), and the albumin-bilirubin (ALBI) score was calculated to be -2.92, resulting in an assignment of ALBI grade 1. Enhanced CT showed enlarged systemic lymph nodes around the abdominal aorta, behind the inferior vena cava, and at the anterior cervical region, suggestive of multiple lymph node metastases (Figure 2).
We started treatment at 1200 mg atezolizumab and 15 mg/kg of body weight bevacizumab every 3 weeks. CT after two cycles of therapy showed mild shrinkage of enlarged lymph nodes and the response rate per RECIST was determined to be stable disease (SD) (Figure 3). Due to the presence of ascites, we interrupted bevacizumab and continued atezolizumab monotherapy at the third, fourth, and fifth cycles. CT after five cycles showed a lasting tumor response. We resumed bevacizumab treatment combined with atezolizumab at the sixth and seventh cycles owing to the improvement of edema by diuretics. We deemed him to have stable diseases on CT after seven cycles of treatment. We continued atezolizumab monotherapy at the eighth and ninth cycles due to bevacizumab-related adverse events, such as fatigue, decreased appetite, and proteinuria. After 10 cycles of treatment, CT showed the regrowth of enlarged lymph nodes and the response rate per RECIST was determined to the progressive disease (PD). Therefore, Atez/Bev treatment was discontinued, and the patient ultimately achieved a 7.5-month progression-free survival (PFS). At 28 months after the initial hepatic treatment (15 months after initiation of systemic therapy), the patient was still alive. The overall clinical course is shown in Figure 4.