hepatocellular carcinoma ( hcc ) is the sixth most common cancer worldwide , and it is the third most common cause of death from cancer .
recent studies demonstrated clinical features of multiple primary malignancies involving hcc [ 2 , 3 ] .
however , hcc patients bearing other malignancies with distal metastasis are not only uncommon , but also difficult to diagnose .
therefore , the therapeutic approach for and the clinical course of these patients remains unclear .
herein , we describe a case of metachronous multiple primary malignancies consisting of hcc and gastric cancer with intracranial metastasis .
a 76-year - old man visited our hospital because of visual disturbance , weakness of the left upper and lower limbs , and gait disturbance .
the patient had been treated for cirrhosis caused by chronic hepatitis c virus ( hcv ) infection . because hcc was detected , approximately 60 mm in diameter , in the right lobe , he had undergone transarterial chemoembolization 3 and 10 years earlier . when radiofrequency ablation was performed for the recurrent hcc 2 years ago ,
the patient had neither a history of smoking nor an elevation of tumor markers for primary lung cancer ( such as squamous cell carcinoma antigen and neuron - specific enolase ) . since the resected gastric cancer histologically lacked an involvement of lymph nodes , we considered the possibility that lung tumors were of hcc origin .
subsequently , sorafenib was administered . because of adverse events such as a hand - foot skin reaction , the dose of sorafenib was reduced from 800 to 200 mg / day . on admission ,
serum levels of hepatobiliary enzymes and renal function markers such as blood urea nitrogen and creatinine were normal .
although blood count tests showed slight anemia ( hemoglobin : 11.5 g / dl ) and thrombocytopenia ( 8.5  10/l ) , his white blood cell count was normal ( 4,000/l ) .
however , the levels of alpha - fetoprotein ( afp ) , des - gamma - carboxy prothrombin ( dcp ) , and carbohydrate antigen 199 ( ca199 ) were within the normal range ( 5.6 ng / ml , 21 u / ml , and 10.2 u / ml , respectively ) . although the patient 's consciousness level was normal [ glasgow coma scale was a full score ( e4v5m6 ) ] , he exhibited left - sided hemifield visual disturbance and left - sided hemiparesis .
enhanced mri revealed an intra - axial tumor in the right occipital cerebral lobe ( fig .
2 ) . taking into consideration the markedly elevated level of carcinoembryonic antigen , but not afp or dcp , we made a preoperative diagnosis of intracranial metastasis of gastric cancer , and a craniotomy of the tumor was performed .
macroscopic examination of the resected specimen revealed that the tumor was yellowish - white , solid , and accompanied by necrosis ( fig .
pathological examination revealed that the tumor was consistent with metastatic adenocarcinoma of gastric cancer origin ( fig .
the patient 's visual disturbance , hemiparesis , and gait disturbance markedly recovered to normal after surgery .
follow - up mri conducted 1 week after the craniotomy revealed the successful removal of the tumor . because a small lesion was detected in the left precentral gyrus , the patient received additional gamma - knife treatment ( 20 gy ) .
sorafenib administration was discontinued and s-1 ( tegafur / gimeracil / oteracil potassium , 50 mg / day ) was administered postoperatively .
he was alive for 5 months after the gamma - knife treatment , without any recurrence .
advances in diagnostic modalities and therapeutic approaches have improved the prognosis of patients with multiple primary malignancies . in the diagnosis of multiple primary malignancies ,
according to the criteria , each of the tumors must be distinct and present a definite picture of malignancy .
it has been reported that the prevalence of multiple primary malignancies varies from 0.7 to 11.7% [ 5 , 6 ] . in western countries , prostate , colon , and
in contrast , gastric cancer predominates in asian countries [ 8 , 9 ] . in our case ,
although multiple lung metastases were observed concurrently , it was difficult to determine whether the tumor was derived from hcc or gastric cancer .
we considered the possibility of hcc origin because of an increase in the serum level of afp and pivka - ii despite the curative treatment of recurrent hcc and histological findings of resected gastric cancer not involving the lymph nodes .
the frequency of intracranial metastasis in patients with gastric cancer ranges from 0.16 to 2.0% [ 10 , 11 ] .
it has been documented that aggressive treatments such as resection and/or whole brain radiation therapy could improve the quality of life and prolong the survival [ 12 , 13 ] . in our case ,
although another intracranial lesion was detected after craniotomy , the tumor was successfully treated with a gamma - knife .
given that the multiple lung tumors gradually enlarged during the administration of sorafenib , it was undeniable that the lung tumors were derived from gastric cancer .
together , these findings indicate the possibility that sufficiently aggressive treatment for intracranial metastasis of gastric cancer enables further anti - cancer treatment and improves the prognosis , even of patients with multiple primary malignancies . when original tumors are radically treated in patients with multiple primary malignancies , further treatment including craniotomy and gamma - knife for the metastatic intracranial tumors might contribute to prolonged survival . considering that intracranial metastasis of gastric cancers is frequently accompanied by bone , liver , and lung metastases [ 10 , 14 ] ,
it is of importance to determine whether or not aggressive treatment , including surgical resection , improves both the performance status and the prognosis of the patients .
 a 76-year - old man was referred to our hospital with visual disturbance , weakness of the left upper and lower limbs , and gait disturbance . 
 he had previously received transarterial chemoembolization for hepatocellular carcinoma ( hcc ) 3 and 10 years ago . 
 when he had received radiofrequency ablation for hcc recurrence 2 years ago , total gastrectomy was also performed for his gastric cancer . 
 subsequently , sorafenib had been administrated for concomitant lung metastatic tumors . on admission 
 , mri revealed an intra - axial tumor with perifocal edema . 
 the level of carcinoembryonic antigen , but not alpha - fetoprotein , markedly increased . 
 the tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma , which was consistent with the primary gastric cancer . 
 after surgery , his neurological disturbances rapidly resolved . 
 additional gamma - knife treatment was also performed for another small brain metastasis detected after craniotomy . 
 subsequently , sorafenib administration was discontinued and s-1 was administered postoperatively . 
 successful treatment of intracranial metastasis of gastric cancer is important and meaningful , even in patients with multiple primary malignancies . 