hepatic resection is still the most effective treatment for hcc ; however , the recurrence rate is very high even after curative resection . the postoperative 5-year recurrence rate was shown to be higher than 70% , with 80% to 95% of recurrence being confined to the liver [ 14 ] . intrahepatic recurrence has been classified as either metachronous multicentric - occurrence hcc ( mc ) or intrahepatic metastasis ( i m ) [ 5 , 6 ] . anatomic hepatic resection has been shown to be effective for micro i m within resected sections or segments with progressed hcc [ 79 ] but is ineffective for mc in the remnant liver . recent studies have shown that hypovascular early hcc ( ehcc ) , which is not an indication for resection , progresses to conventional hypervascular hcc . hypovascular ehcc is thought to be one of the causes of multicentric recurrence of hypervascular hcc after hepatic resection . however , the effects of simultaneous treatment of suspected ehcc at the time of hepatic resection for progressed hcc on postoperative recurrence have never been evaluated . a new magnetic resonance imaging ( mri ) contrast medium , gadoxetic acid , or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ( gd - eob - dtpa ) ( primovist , bayer healthcare , osaka , japan ) , which has the properties of both an extracellular gadolinium chelate and liver - specific ( hepatocyte - targeting ) contrast material , has become available [ 1013 ] . our previous study revealed that gd - eob - dtpa - enhanced mri ( eob - mri ) was the most useful imaging technique for evaluating small hcc , including ehcc . the purpose of this study was to clarify whether preoperative eob - mri and simultaneous treatment of suspected ehcc at the time of resection for progressed hcc affected the overall and recurrence - free survival of patients after initial hepatic resection for hcc . a total of 147 consecutive progressed hcc patients without extrahepatic metastasis who underwent their first curative hepatic resection for hcc at the first department of surgery ( yamanashi university hospital , yamanashi , japan ) between 1 january 2005 and 31 december 2010 were retrospectively enrolled in this study . this study protocol followed the ethical guidelines of the declaration of helsinki amended in 2008 , and written informed consent was obtained from each patient . preoperative imaging studies , including chest radiography , abdominal ultrasonography ( aus ) , computed tomography ( ct ) , mri , hepatic arteriography , ct during arterial portography ( ctap ) , and ct during hepatic arteriography ( ctha ) , were performed . one patient did not undergo contrast - enhanced ct , ctha , or ctap because of an allergy to the iodinated contrast material . in addition , ctha and ctap were not performed in one patient with mild renal dysfunction . , eob - mri has been performed before hepatic resection for hcc as essential imaging diagnostics . in this study , 77 patients underwent eob - mri ( eob - mri ( + ) group ) and the remaining 70 patients underwent conventional mri ( eob - mri (  ) group ) before hepatic resection for hcc . hypovascular hepatic nodules showing low attenuation on unenhanced ct and ctap and those showing low signal intensity on hepatocyte - phase images of eob - mri were diagnosed as suspected ehccs [ 13 , 14 ] . liver function reserve was assessed by liver biochemistry , child - pugh grading , and the indocyanine green retention rate at 15  min ( icgr15 ) . only patients with child - pugh class a and icgr15 below 20% were offered major hepatic resection , which is defined as resection of two or more segments of the liver according to couinaud 's classification . patients with child - pugh class a and icgr15 more than 20% and selected class b patients underwent minor hepatic resection , which is defined as resection of one segment or less of the liver . suspected ehccs detected by preoperative imaging diagnosis with or without eob - mri , and being more than 5  mm in diameter , were simultaneously resected or ablated at the time of resection for progressed hcc . all surgically resected specimens were fixed in 10% buffered formaldehyde . sections of resected tumors and noncancerous livers were embedded in paraffin , sliced into 3 to 5  m thick sections , and were then stained with hematoxylin - eosin for histological analyses . all suspected ehccs were diagnosed strictly according to the pathological criteria proposed by the international consensus group for hepatocellular neoplasia ( icghn )   by pathologists . after the initial operation , patients were followed up at 2-week intervals for the first 2 months and monthly thereafter . serum levels of -fetoprotein ( afp ) , a lens culinaris agglutinin reactive fraction of afp ( afp - l3 ) , and des--carboxy prothrombin ( dcp ) were measured serially at least every 2 months . imaging diagnosis , using ct or mri , was performed at least every 4 months . diagnosis of recurrence was made when intrahepatic hypervascular hcc was found by contrast - enhanced ct , mri , or ctha . if intrahepatic recurrence was 3 nodules and all tumors were potentially resectable in terms of anatomical location and liver function , recurrence was managed using repeat hepatic resection . recurrence was managed using radiofrequency ablation ( rfa ) if intrahepatic recurrence was solitary and completely ablative and hepatic function of the patient was not suitable for repeat hepatic resection or if the patient refused hepatic resection . multiple intrahepatic recurrence ( > 3 nodules ) continuous data are expressed as the median ( range ) and were compared using the mann - whitney u test . categorical variables were compared using the chi - square test with yates ' correction or fisher 's exact test where appropriate . survival was calculated by the kaplan - meier method and compared by means of the log - rank test . univariate and multivariate analyses were performed using the cox proportional hazards model to identify prognostic factors . a comparison of background factors between the eob - mri ( + ) and eob - mri (  ) groups was performed ( table 1 ) . the dcp value of patients in the eob - mri (  ) group was significantly higher than that in the eob - mri ( + ) group ( median : 57  mau / ml ; range : 1230805  mau / ml ; versus 29.0  mau / ml ; 917521  mau / ml ; p = 0.02 ) . the number of patients who underwent treatment for ehccs at the time of hepatic resection was significantly higher in the eob - mri ( + ) group than in the eob - mri (  ) group ( 17 versus 6 ; p = 0.04 ) . no significant differences were observed in the other background factors between groups . in the eob - mri (  ) group , histologically , 6 out of 8 resected tumors were ehcc and two were dysplastic nodules ( dns ) . on the other hand , 24 suspected ehccs from 17 patients were treated in the eob - mri ( + ) group ( 23 were resected and one was ablated by microwaves without biopsy ) at the time of the operation . histological examination revealed that 21 out of 23 resected tumors were ehcc , one was dn , and one was accessory liver . in the eob - mri ( + ) group , 8 out of 21 ehccs ( 38.1% ) were detected at only hepatocyte phase of eob - mri . the 1- , 3- , and 5-year overall survival rates of 77 hcc patients in the eob - mri ( + ) group were 98.7 , 90.7 , and 80.8% , respectively , whereas the corresponding survival rates of 70 hcc patients in the eob - mri (  ) group were 97.0 , 86.3 , and 72.4% , respectively ( figure 1 ) . no significant differences were observed in the overall survival curves between the two groups ( p = 0.38 ) . on the other hand , the 1- , 3- , and 5-year recurrence - free survival rates of 77 hcc patients in the eob - mri ( + ) group were 81.4 , 62.6 , and 48.7% , respectively , whereas those of 70 hcc patients in the eob - mri (  ) group were 82.1 , 41.5 , and 25.5% , respectively ( figure 2 ) . recurrence - free survival after hepatic resection was significantly better in the eob - mri ( + ) group than in the eob - mri (  ) group ( p < 0.01 ) . tables 2 and 3 summarize the results of univariate analysis of the 20 clinical and laboratory factors and 7 pathological and tumor - related factors , respectively , for overall survival and recurrence - free survival among the 147 patients with hcc following curative hepatic resection . in clinical and laboratory factors , the presence of an esophageal varix ( p = 0.02 ) , platelet count 10  10/l or less ( p < 0.01 ) , child - pugh class b ( p < 0.01 ) , and a dcp value more than 40  mau / ml ( p = 0.03 ) were correlated with significantly worse overall survival ( table 2 ) . other clinical and laboratory factors did not show any significant influence on overall survival after hepatic resection for hcc . in pathological and tumor - related factors , the presence of liver cirrhosis ( p = 0.01 ) was correlated with significantly worse overall survival ( table 3 ) . in clinical and laboratory factors , preoperative eob - mri significantly reduced the risk of recurrence ( p < 0.01 ) . on the other hand , a serum albumin level of 3.5  g / dl or less ( p < 0.01 ) , platelet count 10  10/l or less ( p = 0.04 ) , child - pugh class b ( p < 0.01 ) , and being positive for hepatitis c antibodies ( p < 0.05 ) were correlated with significantly worse recurrence - free survival ( table 2 ) . in pathological and tumor - related factors , multiple progressed hccs ( p < 0.01 ) were correlated with significantly worse recurrence - free survival by univariate analysis ( table 3 ) . according to multivariate analysis for factors that could influence overall survival , a platelet count 10  10/l or less ( hr 4.41 , 95% ci 2.049.52 , p < 0.01 ) and dcp value more than 40  mau / ml ( hr 3.55 , 95% ci 1.727.34 , p < 0.01 ) were selected as independent predictors of adverse overall survival of patients with hcc after hepatic resection ( table 4 ) . on the other hand , preoperative eob - mri ( hr 0.56 , 95% ci 0.360.86 , p < 0.01 ) and multiple progressed hccs ( hr 2.10 , 95% ci 1.293.40 , p < 0.01 ) were identified as independent factors significantly correlated with recurrence - free survival after hepatic resection ( table 4 ) . the findings of this retrospective study showed that preoperative eob - mri and simultaneous treatment of ehcc prolonged recurrence - free survival but not overall survival of progressed hcc patients following hepatic resection . univariate and multivariate analyses showed that preoperative eob - mri was one of the independent factors significantly correlated with recurrence - free survival after hepatic resection . to the best of our knowledge , this is the first study to show that simultaneous treatment of ehcc based on the preoperative imaging study including eob - mri prolonged recurrence - free survival after hepatic resection for hcc . a new mr imaging contrast medium , gadoxetic acid , or gd - eob - dtpa , which has the properties of both an extracellular gadolinium chelate and liver - specific contrast material , has become available . injection of a bolus of gd - eob - dtpa allows for the assessment of tumor vascularity using arterial phase imaging and enables hepatocyte - phase imaging approximately 20 minutes after its administration , with approximately 50% of the contrast material being taken up by hepatocytes [ 1013 ] . eob - mri including a gradient dual - echo sequence and diffusion - weighted imaging has been recommended for the pretherapeutic evaluation of patients with hcc . our previous study showed that eob - mri was the most useful imaging technique for evaluating small hcc , including ehcc . hypovascular nodules that appear hypointense on hepatocyte - phase eob - mri may progress to conventional hypervascular hepatocellular carcinoma . we previously showed that nodules more than 10  mm in diameter and containing fat were at a higher risk of developing hypervascularization . moreover , a maximum diameter more than 10  mm   or 15  mm or greater , increased growth rate , hyperintensity on t1-weighted images , hyperintensity on t2-weighted images , and a tumor volume doubling time of less than 542 days   were reported to be risk factors of hypervascularization in hypovascular nodules that appeared hypointense on hepatocyte - phase eob - mri . we showed that preoperative eob - mri and simultaneous treatment of ehcc at the time of resection for progressed hcc prolonged recurrence - free survival after hepatic resection . the recurrence - free survival curves of the two groups overlapped within one year after hepatic resection and after that the incidence of recurrence in the eob - mri ( + ) group became significantly lower than that in the eob - mri (  ) group . we speculate that recurrence within one year of hepatic resection is mainly due to enlargement of preoperatively undetectable intrahepatic micro i m of resected progressed hcc , while recurrence after one year was mc that progressed from ehcc to hypervascular hcc or was de novo hypervascular hcc . we estimate that simultaneous treatment of ehcc at the time of resection for progressed hcc reduced mc by removing ehcc that may have progressed to hypervascular hcc . one of the reasons why preoperative eob - mri and simultaneous treatment of ehcc at the time of resection prolonged recurrence - free survival but not overall survival after hepatic resection for hcc was early diagnosis and prompt treatment of recurrent hcc detected by our postoperative close follow - up . reducing postoperative recurrence after hepatic resection of hcc may not only diminish the burden on patients , but also preserve liver function . the present study showed for the first time that preoperative eob - mri and simultaneous treatment of ehcc prolonged recurrence - free survival of progressed hcc patients following hepatic resection . however , because our data were based on a retrospective study and limited number of patients , further prospective studies are required to fully evaluate the significance of preoperative eob - mri and simultaneous treatment of ehcc .