hepatocellular carcinoma ( hcc ) is one of the most common malignancies and has a high mortality rate worldwide .
hcc usually develops in chronically damaged liver caused by an infection with the hepatitis b virus ( hbv ) or hepatitis c virus ( hcv ) , alcoholic abuse and nonalcoholic fatty liver disease .
recent progress in diagnosis and new therapeutic approaches have improved the survival and prognosis of hcc .
notably , antiviral therapy such as nucleoside analogs in hbv carriers and interferon administration in hcv carriers reduced the risk of hcc [ 3 , 4 ] . however , chronic infection with hbv is often associated with the development of hcc at a young age and in the absence of liver cirrhosis .
patients with hcc in advanced clinical stages still have a dismal prognosis . not only tumor progression but also metastasis determines the prognosis of a wide range of malignancies including hcc .
tumor infiltration of blood vessels at the primary tumor site is responsible for metastasis and causes the formation of metastatic lesions in distant organs .
it has been believed that vascular invasion , which is one of the most significant features of hcc , contributes to intrahepatic or extrahepatic metastasis .
extrahepatic metastases of hcc are frequently observed in distant organs such as the lungs , regional lymph nodes , kidneys and bone marrow .
intracranial metastasis frequently develops in patients with advanced tumors , palliative therapy rather than aggressive treatment tends to be selected .
therefore , both the benefits of treatment and the clinical course of intracranial metastasis of hcc remain to be elucidated . here , we describe a resected case of intracranial metastasis of hcc
. surgical resection of the tumor resulted in a dramatic recovery of consciousness and enabled further therapeutic intervention against hcc .
a 32-year - old man was referred to our hospital because of nausea and vomiting .
he had been monitored for chronic liver disease caused by hbv infection 2 years before . as multiple hcc
was detected in the hepatic right lobe 1 year prior , he underwent a right hepatic trisectionectomy .
since his serum level of hbv - dna was more than 5 log copies / ml at that time , a nucleoside analog , entecavir , was administered . because of recurrence in the residual liver and lung metastasis detected 6 months after surgery , he was treated with an oral multikinase inhibitor , sorafenib . as adverse events such as liver dysfunction and eruption
were observed 1 month after the administration of sorafenib , the dose was reduced from 800 to 200 mg / day . on admission ,
serum levels of hepatobiliary enzymes and markers for renal function such as blood urea nitrogen and creatinine were normal .
although blood count tests showed slight anemia ( hemoglobin 11.2 g / dl ) and thrombocytopenia ( 12.6  10/l ) , his white blood cell count was normal ( 4,800/l ) .
serological tests exhibited the following hbv markers : hepatitis b surface antigen ( hbsag ) positive , hepatitis b surface antibody ( hbsab ) negative , hepatitis b envelope antigen ( hbeag ) negative , hepatitis b envelope antibody ( hbeab ) positive , and hepatitis b core antibody ( hbcab ) positive .
his serum level of hbv - dna measured by real - time polymerase chain reaction was 2.9 log copies / ml .
anti - hcv antibody was negative . although the level of alpha - fetoprotein was elevated to 195,400 u / ml , that of pivka - ii was within the normal range ( 32 u / ml ) . of importance
, the patient 's glasgow coma scale score was 11 points ( e3v4m4 ) , but no paresis was observed .
however , the consciousness level gradually deteriorated and the glasgow coma scale score decreased to 6 points ( e2v2m2 ) on the second day of hospitalization .
non - enhanced computed tomography ( ct ) revealed an intra - axial tumor with surrounding edema in the left frontal lobe ( fig .
the tumor was found to be hyperdense on ct and hypointense on t2-star - weighted images of magnetic resonance imaging ( mri ) consistent with hemorrhage ( fig .
a preoperative diagnosis of intracranial metastasis of hcc was made and a craniotomy was performed .
macroscopic examination of resected specimens revealed that the tumor was grayish - white and accompanied by necrosis and hemorrhage ( fig .
pathological examination revealed that it was a moderately differentiated hcc accompanied by necrosis and hemorrhage ( fig .
follow - up ct conducted 1 week after the craniotomy revealed both successful removal of the tumor and improvement in the subfalcine herniation ( fig .
contrast - enhanced ct showed not only multiple residual hccs with portal vein tumor thrombus ( fig .
3d ) . subsequently , an implanted port - catheter system was constructed and he was treated with hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin .
chronic infection with hbv is known to be a major risk factor for cirrhosis and hcc .
lamivudine was the first nucleoside analog to be approved for the treatment of patients with chronic hbv infection , but drug resistance frequently develops during long - term lamivudine therapy . in contrast , treatment with entecavir , another nucleoside analog against hbv , rarely results in resistance .
recent reports showed that both drugs reduced the risk of developing hbv - related hcc , although an unfavorable virological response to the treatment failed to decrease the incidence of hcc in patients with cirrhosis . in our case , the patient acquired hbv vertically and developed cirrhosis and hcc .
when he started to take entecavir orally after right hepatic trisectionectomy , the hbv - dna decreased but did not disappear in the peripheral blood .
extrahepatic metastases are detected in 1437% of hcc patients , although intracranial metastasis only accounts for a small percentage of extrahepatic metastases .
since intracranial metastasis of hcc frequently causes serious complications such as intracranial hypertension , hemorrhage and cerebral edema , the prognosis of hcc is dismal .
choi et al .   reported that surgical resection and/or whole brain radiation therapy significantly prolonged survival compared with steroid treatment alone .
it has been also documented that aggressive treatments such as resection and/or whole brain radiation therapy , single intracranial metastasis , and good liver reserve function serve as a prognostic factor .
together , these findings indicate that sufficiently aggressive treatment may improve the prognosis for some patients with intracranial metastasis of hcc . in our case
, there was only one metastatic lesion and the patient 's liver reserve function was good ( child - pugh a ) .
successful resection of the intracranial tumor improved his level of consciousness dramatically and enabled further therapeutic approaches against hcc .
together , it seems that surgical resection of intracranial metastasis of hcc contributed to the prolonged survival in this case . in conclusion , we report a rare case of intracranial metastasis of hcc resected successfully . considering that most extrahepatic metastases of hcc developed in patients with advanced intrahepatic lesions and vascular invasion , it is important to be aware of extrahepatic spread in patients with advanced hcc .
in addition , it is necessary to determine whether aggressive treatment such as surgical resection improves the prognosis for intracranial metastasis of hcc .
further examinations in large numbers of patients are necessary for both an understanding of the mechanisms underlying intracranial metastasis of hcc and the development of therapeutic approaches .
 intracranial metastasis of hepatocellular carcinoma ( hcc ) is rare , but has an extremely poor prognosis . 
 we report a case with successful surgical removal of intracranial metastasis of hcc . 
 a 32-year - old man was admitted to our hospital with severe vomiting . 
 he had been followed for liver cirrhosis due to hepatitis b virus infection and received a right hepatic trisectionectomy for hcc 1 year earlier . for the recurrence of hcc 
 , sorafenib had been administered 6 months before admission . on admission , he exhibited consciousness disturbance , which gradually worsened . 
 two days later , both computed tomography and magnetic resonance imaging revealed an intra - axial tumor with perifocal edema and hemorrhage in the left frontal lobe . 
 the tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of moderately differentiated hcc cells . the day after surgical resection of the tumor , his consciousness returned to normal . 
 subsequently , he was treated with hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin using an implanted port - catheter system . 
 surgical resection of intracranial metastasis of hcc would be important and meaningful in some cases . 
Introduction
Case Report
Discussion
Disclosure Statement