Liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis

Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.

Primary multifocal cystic signet ring neuroendocrine tumor of liver: a case report

Primary signet ring neuroendocrine tumors of the liver are extremely rare tumors. Morphologically, they mimic signet ring cell adenocarcinomas; however, the absence of mucin by special stains and the expression of neuroendocrine markers help to diagnose these tumors. We herein report a case of a 47-year-old female who presented with multiple solid and cystic lesions in both liver lobes, which were initially suggested to be biliary cystadenocarcinoma on imaging. Liver biopsy of the lesion revealed the presence of a signet ring neoplasm with diffuse expression of synaptophysin and pan-cytokeratin. The case was subsequently diagnosed as a primary hepatic signet ring neuroendocrine tumor. The patient was offered 3 cycles of chemotherapy and is well preserved after 14 months of diagnosis. Although this is an extremely rare entity, its possibility should be considered in the differential diagnosis of neoplasms characterized by signet ring cell morphology.

A case report of a patient presented with skin ulcer after treatment of lenvatinib

A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.

Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report

The current Food and Drug Administration-approved systemic treatments for advanced hepatocellular carcinoma (HCC) include multikinase inhibitors (tyrosine kinase inhibitor [TKI]) and immune checkpoint inhibitors (ICIs). Among ICIs, nivolumab is used as secondline therapy for advanced HCC after sorafenib failure or patient intolerance. In this case, a patient with infiltrative HCC and portal vein tumor thrombosis was treated with hepatic arterial infusion chemotherapy (HAIC) and radiation therapy. New lung metastasis developed after HAICs; thus, lenvatinib treatment was initiated. However, the disease progressed. Thereafter, sorafenib treatment was initiated but he developed intolerance, with grade 3 sorafenib-related diarrhea. Subsequently, nivolumab was administered as rescue therapy. He demonstrated a partial response to nivolumab after the third treatment and viable HCCs in the lungs and liver completely disappeared after the 24th treatment. These findings suggest that nivolumab could be used as an effective rescue therapy for advanced HCC progression after TKI treatment.

Complete response in hepatocellular carcinoma with lymph node metastasis by combination therapy of atezolizumab and bevacizumab: a case report

Sorafenib is the oldest first line systemic treatment in patients with advanced hepatocellularcarcinoma (HCC) and has been used exclusively for nearly 10 years. The superiority ofadministering a combination of atezolizumab plus bevacizumab (AteBeva) compared tosorafenib as first line systemic treatment for unresectable HCC was recently proven duringthe IMbrave150 Phase III randomized trial. While clinicians can expect improved responsesand treatment outcomes due to the good results of the IMbrave 150 trial, they must alsoconsider that atezolizumab can cause various immune-related adverse events (IrAEs). Basedon the above suggestions, we herein present a case of HCC with lymph node metastasiswho achieved complete remission following treatment with AteBeva and developed an IrAE(adrenal insufficiency). Further study of real-life data regarding combination therapy withAteBeva is needed to manage patients with advanced HCC.

Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment

Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

Curative liver transplantation after lung resection for advanced hepatocellular carcinoma with lung metastasis and inferior vena cava tumor thrombosis: a case report

Hepatocellular carcinoma (HCC) with distant metastasis is an absolute contraindication for liver transplantation (LT). However, it is still unclear whether LT is feasible or acceptable in such patients, albeit after being treated with a multidisciplinary approach and after any metastatic lesion is ruled out. We report one such successful treatment with living donor LT (LDLT) after completely controlling far-advanced HCC with inferior vena cava tumor thrombosis and multiple lung metastases. The patient has been doing well without HCC recurrence for eight years since LDLT. The current patient could be an anecdotal case, but provides a case for expanding LDLT indications in the context of advanced HCC and suchlike.

Long-term survival after multimodal treatment involving radiotherapy for huge hepatocellular carcinoma with oligometastasis: a case report

The clinical efficacy of local ablative treatment for oligometastasis is widely accepted in most cancers. However, due to limited data, this has not been the case for hepatocellular carcinoma (HCC). Here, we report a case of pulmonary oligometastasis of a huge HCC that was treated by multimodality with liver-directed concurrent chemoradiotherapy (CCRT) plus subsequent resection of the primary lesion and local ablative radiotherapy (RT) for subsequent lung oligometastatic lesions. In this patient, liver-directed CCRT induced significant tumor shrinkage with compensatory hypertrophy of the non-tumor liver, followed by curative resection. Surgical resection of the first and second pulmonary metastatic lesions as well as local ablative RT of the third lesion achieved complete tumor regression, which led to long-term survival of 6 years. Therefore, the active use of local ablative RT requires full consideration in cases of oligometastatic HCC.

The effect of nucleos(t)ide analogues on clinical outcomes of patients treated with transarterial chemoembolization and radiofrequency ablation for hepatitis B virus-related hepatocellular carcinoma

Background/Aims: Because hepatitis B virus (HBV) replication has been known to play animportant role in cancer recurrence after curative treatment of HBV-related hepatocellularcarcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs)might decrease the recurrence rate and improve patient survival.Methods: The retrospective cohort study enrolled 73 patients with chronic hepatitis B whowere treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA)with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovirdisoproxil fumarate (TDF) and entecavir (ETV), respectively.Results: Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were deadduring a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazardratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B(vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associatedwith HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was anindependent unfavorable prognostic factor for survival. During NAs therapy, TDF was superiorto ETV for complete viral response at 1 year after the date of combination of TACE and RFA(P=0.016). However, the risks of HCC recurrence and survival were not significantly differentbetween those treated with TDF versus ETV.Conclusions: TDF was superior to ETV for achieving complete viral response. However, therecurrence and mortality after TACE and RFA for HBV-related HCC were not significantlydifferent between patients treated with TDF versus ETV.