hepatocellular carcinoma ( hcc ) is a common malignancy and is now one of the major causes of death in asian countries . generally , hccs are often asymptomatic , but fatigue , abdominal distention and low - grade fever
however , fever as a primary symptom in hcc is relatively rare . additionally , high crp in laboratory results is also rare .
hcc with pyrexia has been reported only in a few studies [ 24 ] and the cause of pyrexia has remained unknown .    recently , increased production of proinflammatory cytokines and chemokines , such as interleukin-1  ( il-1 ) , interleukin-1  ( il-1 ) , interleukin-6(il-6 ) , interleukin-8(il-8 ) , and tumor necrosis factor- ( tnf- ) have been reported to be febriferous in acute and chronic inflammatory disease [ 5 , 6 ] . these cytokines are produced by immune cells including various populations of lymphocytes macrophages and other cells . among the proinflammatory cytokines ,
il-8 is a neutrophil chemotactic factor and involved in tumor proliferation and migration , angiogenesis in malignant tumors .
this is often accompanied by rapid growth and poor prognosis in malignant tumors [ 713 ] .   
we herein discuss a case of hcc accompanied by prolonged spiking fevers , which disappeared after tumor resection .
a 50-year - old man with a history of liver dysfunction was admitted to iizuka hospital with the chief complaint of a prolonged fever and general fatigue in october , 2005 .
hematological laboratory data on admission were as follows : wbc 9670/ l , alp 552 u / l , crp 16.7 mg / dl , and afp 11.1 ng / ml .
hbs - antigen was positive ( table 1 ) . a computed tomography ( ct ) showed a peripherally enhanced low density mass 7.5 cm in diameter , which located in segment 6 in the right lobe of the liver ( figure 1(a ) ) .
the tumor was accompanied with tumor thrombus to the posterior branch of portal vein ( figure 1(b ) ) .
celiac angiography showed this lesion was hypervascular ( figure 1(c ) ) and portal vein tumor thrombus in posterior segment was observed in the portal phase ( figure 1(d ) ) .   
patients have chronic hepatitis b and then tumor was hypervascular and accompanied with portal thrombus , which is the feature of hcc , therefore a preoperative diagnosis was made as hcc with portal vein thrombus and nonsteroidal anti - inflammatory drugs were used to reduce the fever .
a single nodule of disseminated cancer cells was found near the posterior segment on the abdominal wall during the operation .
posterior segmentectomy of the liver and thrombectomy including the dissemination was performed . on the cut section ,
the noncancerous liver tissue showed a moderate chronic inflammatory infiltrate in the fibrous stroma , diagnosed as liver fibrosis .
immunohistochemical stain of il-8 was performed with paraffin embedded sections of liver tissue using mouse monoclonal antibody at dilutions of 1 : 100 ( assay designs , ann arbor , usa ) .
the subsequent reaction was performed by the peroxidase labeled streptavidin - biotin technique using histofine sab - po kit ( nichirei , tokyo , japan ) .
il-8 was observed in the cytoplasm of cancer cells ( figure 3(b ) ) .   
after the tumor resection , fever disappeared and crp dropped gradually from 16.7 to 2.7 , but the patient had recurrence with multiple liver metastasis and pleuritis carcinomatosa and died on february 2 , 2006 , 79 days after the operation .
in 1991 , okuda et al .   reported five patients with hcc and pyrexia , for an incidence of less than 1% , in japan .
he also mentioned that very poorly differentiated sarcomatoid hcc may frequently appear with pyrexia and leukocytosis mimicking liver abscess . in 1995 , hayashi et al .   reported hcc with pyrexia
laboratory data revealed high crp . nevertheless , in both case reports , the mechanism of a fever was not revealed . in our case ,
the sarcomatoid change of the cancer cell was not detected , only poorly differentiated hcc .   
it is well known that cancer cells produce humoral factors and cause the  paraneoplastic syndrome  . among the clinical symptoms and laboratory data , fever and high crp ,
which is not commonly observed in the patients with hcc , is suspected to be due to humoral factors , especially inflammatory cytokine .
il-8 is a proinflammatory cytokine whose principal role in infection and inflammation appears to be the recruitment and activation of circulating and tissue neutrophils to the site of tissue damage .
it has been demonstrated that il-8 is produced by a wide variety of cell types in vitro , including endothelium , monocytes , eosinophils , astrocytes and keratinocytes . in sepsis patients , for example ,
il-8 concentrations have been reported as being markedly elevated at diagnosis and remaining high during the course of the illness .
this symptom is induced by many humoral factors , including il1 , il-6 , il8 and tnf. zampronio ar reported that il-8 induced fever by prostaglandin independent mechanism .
il-8 resulted in a dose - dependent increase of crp , a decrease in the production of transferring and prealbumin .
therefore , il-8 is related to pyrexia in parts , not all .    in other cancer ,
we examined by immunohistochemical staining of il-8 and tumor tissue stained positive for il-8 in this case .
akiba et al .   reported that a high il-8 level in hcc had a significantly higher frequency of portal vein invasion and venous invasion and bile duct invasion . in vitro
reported il-8 production was enhanced progressively with escalating severity of hepatitis and the development of hcc and the level of il-8 were significantly increased in patients with advanced hcc with distant metastasis , and then this leads to poor prognosis .
ren et al . reported serum il-8 level was correlated with tumor size and tumor stage , and then il-8 level was a significant prognostic factor in terms of disease - free survival and overall survival .
additionally , elevated il-8 levels in the drainage vein of colorectal cancer are related to the occurrence of hepatic metastasis .
this case presented portal vein tumor thrombus , bile duct invasion , intrahepatic metastasis , peritoneal dissemination , early tumor recurrence , rapid tumor regrowth and finally a poor prognosis .
in fact , all patients with il-8 production do not have a high fever , the serum concentration of il-8 or the degree of neutrophil infiltration will be concerned with pyrexia .    in many cancers such as esophageal cancer , gastric cancer and colorectal cancer ,
serum crp was known as a prognostic indicator [ 2023 ] . in particular , some reported that serum crp levels indicated a poor prognosis in hcc patients and portal vein invasion was significantly higher in the serum crp - positive group [ 24 , 25 ] . according to the in vitro previous studies , cultured hcc can produce crp that is regulated in part by proinflammatory cytokines , such as il-6 , il-8 and tnf- [ 18 , 26 , 27 ] . among the many proinflammatory cytokines , recent report il-6 mediates cell cycle arrest in hepatocellular carcinoma through a stat 3-dependent pathway
hcc produce proinflammatory cytokines such as il-8 by autocrine or paracrine , which lead to crp production and inflammatory cascade or tumor progression .   
in this report we discussed a patient who had poorly differentiated hcc with pyrexia and high crp .
il-8 production was histologically revealed in this case and may have contributed to the high fever , high inflammatory reaction and poor prognosis .
 we discuss a patient who had poorly differentiated hcc with pyrexia and high crp in laboratory data , which are not commonly observed in the usual hcc . 
 a 50-year - old man with a history of liver dysfunction was admitted with a chief complaint of a prolonged fever and general fatigue . 
 preoperative diagnosis was hcc with portal vein tumor thrombus . 
 posterior segmentectomy of the liver and thrombectomy was performed . 
 rapid tumor recurrence occurred after surgery , and he died 79 days after the operation . 
 immunohistochemical stain of hcc in this patient revealed the production of proinflammatory cytokine , interleukin-8 ( il-8 ) . 
 il-8 production may have contributed to the high fever , high inflammatory reaction , and poor prognosis in this case . 