• Case report
• Extrahepatic
• Lymph node
• Metastasis
• Portocaval

Metastasis occurs as a late event in the natural history of hepatocellular carcinoma (HCC), and most patients die of liver failure attributed to the tumor supplanting the liver. Conversely, the brain is a less common metastatic site.

We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus, Meckel’s cave, and the petrous bone involving multiple cranial nerves in an 82-year-old woman. At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) revealed multiple HCC nodules in both right and left lobes. Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC. Molecular targeted therapy with Lenvatinib (8 mg/d for 94 d, per os) and Ramucirumab (340 mg/d and 320 mg/d, two times by intravenous injection) were administered for 4 mo, resulting in progression of the disease. Three months after the start of molecular target therapy, the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye, indicating disturbances in the right trigeminal and abducens nerves. Brain MRI disclosed a mass involving the cavernous sinus, Meckel’s cave and the petrous bone. Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave.

The diagnosis of metastatic HCC to the cavernous sinus, Meckel’s cave, and the petrous bone was made based on neurological findings and imaging studies including MRI, but not on histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

• Meckel’s cave
• Abducens nerve
• Trigeminal nerve
• Hepatocellular carcinoma
• Magnetic resonance imaging
• Case report

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, which usually arises in cirrhotic liver. When the typical enhancement pattern, consisting of late arterial hyperenhancement followed by washout, is present in nodules larger than 1 cm, HCC can be confidently diagnosed without the need for tissue biopsy. Nevertheless, HCC can display an atypical enhancement pattern, either as iso or hypovascular lesion, or hypervascular lesion without washout. Not only the enhancement pattern of HCC could be atypical, but also a variety of histological types of HCC, such as steatotic, scirrhous, fibrolamellar, or combined hepatocellular-cholangiocellular carcinoma could raise diagnostic dilemmas. In addition, distinct morphological types of HCC or different growth pattern can occur. Awareness of these atypical and rare HCC presentations on magnetic resonance imaging is important for accurate differentiation from other focal liver lesions and timely diagnosis, which allows optimal treatment of patients.

• Hepatocellular carcinoma
• Cirrhosis
• Magnetic resonance imaging
• Hepatocarcinogenesis

• Bile Duct Neoplasms/diagnosis
• Biopsy
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Cholangiocarcinoma/diagnosis
• Diagnosis, Differential
• Fatty Liver/diagnosis
• Hepatectomy
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver/surgery
• Liver Cirrhosis/diagnosis
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Magnetic Resonance Imaging
• Preoperative Period

The incidence of bone metastases (BMs) from hepatocellular carcinoma (HCC) is relatively low compared to those of other cancers, but it has increased recently, especially in Asian countries. Typically, BMs from HCC appear radiologically as osteolytic, destructive, and expansive components with large, bulky soft-tissue masses. These soft-tissue masses are unique to bone metastases from HCC and often replace the normal bone matrix and exhibit expansive growth. They often compress the peripheral nerves, spinal cord, or cranial nerves, causing not only bone pain but also neuropathic pain and neurological symptoms. In patients with spinal BMs, the consequent metastatic spinal cord compression (MSCC) causes paralysis. Skull base metastases (SBMs) with cranial nerve involvement can cause neurological symptoms. Therefore, patients with bony lesions often suffer from pain or neurological symptoms that have a severe, adverse effect on the quality of life. External-beam radiotherapy (EBRT) can effectively relieve bone pain and neurological symptoms caused by BMs. However, EBRT is not yet widely used for the palliative management of BMs from HCC because of the limited number of relevant studies. Furthermore, the optimal dosing schedule remains unclear, despite clinical evidence to support single-fraction radiation schedules for primary cancers. In this review, we outline data describing palliative EBRT for BMs from HCC in the context of (1) bone pain; (2) MSCC; and (3) SBMs.

• Hepatocellular carcinoma
• Metastasis
• Radiotherapy
• Palliative therapy
• Spinal cord compression
• Skull base metastasis

This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC. He presented to our department with a three-month history of increasing left otalgia, and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective, the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone, all of which mainly metastasized in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.

• Hepatocellular carcinoma
• Metastasis
• External auditory canal

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

• Hepatocellular carcinoma
• Distant metastasis
• Skull base
• Cranial nerve

• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/secondary
• Cranial Nerve Neoplasms/diagnosis
• Cranial Nerve Neoplasms/secondary
• Female
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Magnetic Resonance Imaging
• Middle Aged
• Neoplasm Metastasis/diagnosis
• Neoplasm Metastasis/pathology
• Skull Base Neoplasms/diagnosis
• Skull Base Neoplasms/secondary
• Tomography, X-Ray Computed

AIM: To clarify the safety and feasibility of hepatectomy for huge hepatocellular carcinoma (HCC).

METHODS: A total of 4765 patients with HCC operated at Tongji Hospital were retrospectively studied, of them, 780 patients had huge HCC (10 cm or more in diameter). Hepatectomy was carried out on 634 patients (81.2%). The majority of the liver resection were major resections, and combined resection of the adjacent organs or structures was common (17.2%). The liver resection was combined with portal vein thrombectomy in 139 patients (21.9%).

RESULTS: Postoperative complications were common (26.8%) and required another laparotomy to prevent the complications in 5 patients (0.8%). The 30-d mortality was 2.2%. The main causes of postoperative deaths were liver failure (n = 9), postoperative bleeding (n = 4) and septic complication (n = 1). The 3-, 5- and 10-year survival rates after liver resection were 35.1%, 18.2% and 3.5%, respectively.

CONCLUSION: Hepatectomy for huge HCC is safe and effective. It should be used to treat patients with low surgical risks and resectable tumours.

• Hepatectomy
• Huge hepatocellular

• Adult
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Female
• Hepatectomy/adverse effects
• Hepatectomy/methods
• Humans
• Incidence
• Liver/pathology
• Liver/surgery
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Postoperative Complications/epidemiology
• Retrospective Studies
• Survival Analysis

AIM: To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) and to evaluate its prognostic value.

METHODS: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated.

RESULTS: Compared with the healthy volunteers (17.6 ± 9.5 ng/mL), a significant higher circulating DNA level was found in the patients with HCC (47.1 ± 43.7 ng/mL, P = 0.000) or with liver cirrhosis (30.0 ± 13.3 ng/mL, P = 0.002). The circulating DNA level was closely associated with tumor size (P = 0.008) and TNM stage (P = 0.040), negatively associated with the 3-year disease-free survival (DFS) (P = 0.017) and overall survival (OS) (P = 0.001).

CONCLUSION: Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.

• Hepatocellular carcinoma
• Prognosis
• Circulating DNA

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/pathology
• DNA, Neoplasm/blood
• Humans
• Liver Cirrhosis/blood
• Liver Neoplasms/blood
• Liver Neoplasms/pathology
• Middle Aged
• Prognosis
• Severity of Illness Index
• Survival Analysis

AIM: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. It is unclear how osteopontin is regulated in HepG2 cells. The aim of this study was to investigate the effect of epidermal growth factor on the expression of osteopontin in HepG2 cells, and to explore the signal transduction pathway mediated this expression.

METHODS: Osteopontin expression was detected by RNAase protection assay and Western blot. Wortmannin, a specific inhibitor of PI3K, was used to see if PI3K signal transduction was involved in the induction of osteopontin gene expression.

RESULTS: HepG2 cells constitutively expressed low levels of osteopontin. Treatment with epidermal growth factor increased osteopontin mRNA and protein level in a dose-and time-dependent manner. Application of wortmannin caused a dramatic reduction of epidermal growth factor-induced osteopontin expression.

CONCLUSION: Osteopontin gene expression can be induced by treatment of HepG2 cells with epidermal growth factor. Epidermal growth factor may regulate osteopontin gene expression through PI3K signaling pathway. Several potential targets in the pathway can be manipulated to block the synthesis of osteopontin and inhibit liver cancer metastasis.

• Androstadienes/pharmacology
• Carcinoma, Hepatocellular
• Cell Line, Tumor
• Enzyme Inhibitors/pharmacology
• Epidermal Growth Factor/pharmacology
• Gene Expression/drug effects
• Humans
• Liver Neoplasms
• Osteopontin
• Phosphatidylinositol 3-Kinases/metabolism
• Phosphoinositide-3 Kinase Inhibitors
• Sialoglycoproteins/genetics
• Signal Transduction/drug effects
• Signal Transduction/physiology
• Wortmannin

AIM: To investigate the expression of p28/gankyrin gene and its role in the carcinogenetic process of human hepatocellular carcinoma (HCC).

METHODS: 64 specimens of HCC and para-carcinoma tissues, 22 specimens of non-tumor liver tissues (7 normal, 15 cirrhosis), 10 specimens of normal human tissues and 5 hepatoma cell lines were studied for the expression of p28/gankyrin by Northern blot. The expression of p28/gankyrin protein was detected immunohistochemically by using the specific polyclonal antibody.

RESULTS: Northern blot analysis indicated that the expression of p28/gankyrin mRNA was intensively distributed in brain and heart, weakly in lung, spleen and muscle, undetectable in digestive system including liver, pancreas, stomach, small and large intestines. p28/gankyrin mRNA was absent in normal liver, weakly detected in liver cirrhosis and in 18 of 64 para-carcinoma liver tissues. In contrast, the expression of p28/gankyrin mRNA was intensively detected in all 5 hepatoma cell lines tested, markedly increased in 57 of 64 and moderately increased in 5 of 64 HCC samples. In comparison with liver cirrhosis and para-carcinoma liver tissues, the average expression of p28/gankyrin mRNA in HCC was increased 3.6- (2.901 ± 0.507 vs 0.805 ± 0.252, P < 0.05) and 5.2-fold (2.901 ± 0.507 vs 0.557 ± 0.203, P < 0.01), respectively. In addition, p28/gankyrin mRNA expression level was higher in HCC with portal vein tumor thrombus and microscopic hepatic vein involvement (P = 0.021 and P = 0.047, respectively). The overexpression of p28/gankyrin protein in HCC was targeted in hepatic tumor cells, not in bile duct cells and other interstitial cells.

CONCLUSION: Overexpression of p28/gankyrin in HCC plays an important role and contributes to the metastasis potential in the process of carcinogenesis. p28/gankyrin may become a specific biological tissue marker for the pathological diagnosis of HCC.

• Adult
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Female
• Gene Expression
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Oncogene Proteins/genetics
• Oncogene Proteins/metabolism
• Proteasome Endopeptidase Complex
• Proto-Oncogene Proteins
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• Tissue Distribution
• Tumor Cells, Cultured

• liver neoplasms
• axilla
• lymph nodes
• lymphatic metastasis
• case report