ruptured hepatocellular carcinoma ( hcc ) requires immediate diagnosis and treatment due to its high mortality .
the diagnosis is comparatively easy when made based on clinical course , symptoms , and demonstration of hemorrhagic ascites by abdominal paracentesis , but identification of sites of bleeding is important for immediate treatment .
contrast - enhanced computed tomography ( cect ) is performed for identification of these sites in many cases because a wide area can be observed . however , cect is invasive because of iodine allergy , exposure to radiation , and decreased renal function by administration of the contrast agent .
contrast - enhanced ultrasonography ( ceus ) is a non - invasive alternative approach that may be useful for identification of bleeding sites [ 2 , 3 ] .
we experienced a case of ruptured hcc that developed as a complication of alcohol - related cirrhosis .
the patient had multiple hccs , but the culprit artery was readily treated with transarterial embolization ( tae ) after identification of the bleeding site using ceus with sonazoid ( daiichi sankyo pharmaceutical , tokyo , japan ) . here
he had no relevant medical or family history , but he was a heavy drinker who consumed > 2  l of beer every day .
he visited a nearby hospital for a chief complaint of general malaise and was diagnosed with multiple hccs caused by alcohol - related cirrhosis .
approximately 1  month after the first visit , he was admitted to our hospital for rapid development of abdominal fullness .
physical findings at admission showed blood pressure 148/98  mmhg , pulse rate 64  bpm , ascites retention , and a palpable fist - sized tumor in the epigastric region .
blood tests upon admission showed hb 10.4  g / dl ( normal 14.017.0  g / dl ) , ast 55  u / l ( normal 1235  u / l ) , alt 35  u / l ( normal 631  u / l),-gtp 283  u /
l ( normal 958  u / l ) , t - bil 4.9  mg / dl ( normal 0.11.0  mg / dl ) and pt  % 68  % ( normal 70  % ) , suggesting mild anemia and increased hepatobiliary enzymes .
tumor markers were high , as shown by the levels of afp and pivka ii of 27.4  ng / ml ( normal 0.015.0  ng / ml ) and 567  mau / ml ( normal < 40  mau / ml ) , respectively .
hemorrhagic ascites was found in abdominal paracentesis and the case was diagnosed as ruptured hcc .
abdominal cect showed a large hcc with a maximum diameter of 15  cm in s7/8 of the liver and multiple hccs in both lobes ( fig .  1 ) .
the attenuation value of the ascites was as high as 30 hounsfield units , but no clear extravasation was found in the arterial and equilibrium phase , and thus the bleeding site could not be identified .
abdominal ultrasonography also showed multiple tumors in both lobes and ascites with high echo density ( fig . 
however , even with these data the bleeding site was unclear , and ceus was performed for the large hcc in s7/8 as the region of interest .
the ultrasound equipment used in this examination was ssa-790a ( toshiba medical systems , tokyo , japan ) with a convex probe ( pvt-375bt , 3.75-mhz center frequency ) .
the imaging mode used was wideband harmonic imaging ( pulse subtraction ) with transmission / reception frequencies of 1.8 and 3.5  mhz , respectively .
the mechanical index for acoustic output was set to 0.2 ; the dynamic range was set to 6065  db .
a intravenous bolus injection of sonazoid ( 0.5  ml ) was administered via a left cubital venous line followed by 10  ml normal saline flush .
observation in the arterial phase showed no clear leakage of contrast agent from this tumor , but punctate high - intensity echoes of sonazoid microbubbles were observed in ascites . in particular ,
extremely high - intensity echoes of sonazoid microbubbles were present in ascites surrounding the tumor , close to the s5 gallbladder bed .
the tumor was imaged again using the re - injection method   with sonazoid in the post - vascular phase and leakage of the contrast agent from the tumor into the abdominal cavity was observed , indicating that this was the site of bleeding ( fig . 
.  1dynamic computed tomography scan in the arterial phase showed multiple hypervascular lesions in both hepatic lobes with highly attenuated peritoneal fluidfig .  2 
 a gray - scale ultrasonography demonstrated a lesion closed to the s5 gallbladder bed ( arrow heads ) with fluid .
b contrast - enhanced ultrasonography ( ceus ) using the re - injection method with sonazoid in the post - vascular phase showed pulsating active bleeding as extravasation of microbubbles ( arrow ) from this lesion ( arrow heads ) into the abdominal cavity dynamic computed tomography scan in the arterial phase showed multiple hypervascular lesions in both hepatic lobes with highly attenuated peritoneal fluid 
 a gray - scale ultrasonography demonstrated a lesion closed to the s5 gallbladder bed ( arrow heads ) with fluid .
b contrast - enhanced ultrasonography ( ceus ) using the re - injection method with sonazoid in the post - vascular phase showed pulsating active bleeding as extravasation of microbubbles ( arrow ) from this lesion ( arrow heads ) into the abdominal cavity abdominal angiography was urgently performed .
however , since the tumor on the gallbladder bed was suspected as the bleeding site based on ceus , selective cannulation of the cystic artery was performed ( fig . 
the artery was imaged using carbon dioxide ( co2 ) , which is a highly sensitive method for evaluation of blood flow .
leakage of co2 out of the vessel was apparent , confirming that the bleeding site was the tumor in s5 , which was fed by the cystic artery ( fig . 
tae was conducted using a gelatin sponge ( gelpart ; astellas pharma , tokyo , japan ) with a particle size of 1  mm , and the clinical course after tae was favorable with arrest of bleeding.fig . 
3 
 a cystic angiography findings showed multiple tumor stains without extravasation of contrast agent .
b cystic angiography findings with carbon dioxide showed extravasation ( arrow ) . these findings agreed with the ceus findings 
 a cystic angiography findings showed multiple tumor stains without extravasation of contrast agent .
b cystic angiography findings with carbon dioxide showed extravasation ( arrow ) . these findings agreed with the ceus findings
ruptured hcc is a common cause of acute non - traumatic intra - abdominal hemorrhage and has an incidence of about 10  % in patients with terminal hcc . ruptured hcc causes severe intraperitoneal bleeding and acute hepatic failure with a poor prognosis , and therefore immediate diagnosis and treatment are required .
symptoms include sudden epigastric pain or right hypochondrial pain caused by rapid expansion of glisson s capsule .
hemorrhagic shock is observed in 5990  % of patients with ruptured hcc , peritoneal irritation and abdominal prominence occur in 60100  % , and hemorrhagic ascites is present in almost all patients [ 7 , 8 ] .
ruptured hcc should be the first suspected condition when such symptoms occur in patients with cirrhosis or hcc . ruptured
hcc may be a rupture of a parasitic artery or vein , such as the inferior phrenic vessel , feeding or draining the tumor , with accompanying hemorrhage .
this rupture may be caused by secondary trauma to a tumor on the surface of the liver or increased pressure within a tumor due to rapid tumor growth causing invasion and obstruction of a hepatic vein .
the risk of rupture is particularly high in patients with large hcc on the hepatic surface , and the clinical course of such cases should be observed carefully , taking this risk into account . in our case with multiple hccs ,
ruptured hcc was suspected and abdominal paracentesis was performed because of rapid onset of abdominal fullness , which suggested hemorrhagic ascites , despite no abdominal pain or decreased blood pressure .
identification of the bleeding site is important to facilitate immediate treatment in a case of suspected ruptured hcc .
this is commonly achieved with cect , but there is a possibility that a bleeding site may not be apparent in an image due to the imaging timing , even if active hemorrhage is present .
this is because cect has superior spatial resolution , but requires a certain period of time for imaging .
several recent reports have suggested that ceus with levovist ( schering , berlin , germany ) or sonazoid may also be useful for this purpose [ 2 , 3 ] . in 10 patients with ruptured hcc who underwent ceus with levovist and abdominal angiography , matsumoto et al
.   found that ceus could be used to differentiate active hemorrhage from inactive hemorrhage by examining the contrast agent in ascites .
.   found that ceus with sonazoid was effective for identification of the bleeding site in a hepatic surface after radiofrequency ablation ( rfa ) based on a jet - like high - intensity echo in pleural effusion , although the findings could not be confirmed with color doppler imaging .
other reports   have suggested the usefulness of ceus with levovist for large ruptured hcc in cases of single tumors , large tumors , or tumors in which bleeding sites were identified for bleeding caused by rfa .
the high temporal resolution of ceus is useful for evaluation of hemodynamics , but identification of bleeding sites is difficult in patients with multiple hccs because ceus evaluates only a single cross - sectional image .
however , the bleeding site in our case could not be identified with cect because of the presence of multiple hccs , in contrast to previous cases , whereas ceus enabled identification of the bleeding site . in our case
, active hemorrhage was suspected because of leakage of sonazoid bubbles in ascites observed in the arterial phase .
this led to a detailed examination of potential hcc under the hepatic surface , which has a risk of rupture in a case with multiple hccs .
many sonazoid bubbles were found in ascites around hcc on the s5 gallbladder bed , and thus bleeding from this site was suspected .
sonazoid was again intravenously injected using the re - injection method with this site as an area of interest and leakage of contrast agent from the tumor surface was confirmed . in subsequent abdominal angiography
, selective cannulation was performed for the cystic artery based on ceus findings and imaging with co2 showed extravasation from the hcc .
extravasation may not be observed on cect in patients with multiple hccs , as seen in our case , but bleeding sites may be indicated by sonazoid microbubbles in the ascites .
the re - injection method   with sonazoid to examine the potential bleeding site in the post - vascular phase in ceus permits the site to be identified rapidly , even in patients with multiple hccs . in conclusion , we experienced a case of ruptured hcc .
the patient had multiple hccs , but the culprit artery was readily treated with tae after identification of the bleeding site using ceus with sonazoid .
 the identification of bleeding sites of ruptured hepatocellular carcinoma ( hcc ) is important for immediate treatment . 
 we experienced a case of ruptured hcc readily treated with transarterial embolization ( tae ) after identification of the bleeding site using contrast - enhanced ultrasonography ( ceus ) with sonazoid . 
 we report the case of a 61-year - old male with multiple hccs caused by alcohol - related cirrhosis , who was admitted for rapid development of abdominal fullness . 
 the diagnosis was established by hemorrhagic ascites by abdominal paracentesis . 
 no clear extravasation was found on contrast - enhanced computed tomography . 
 ceus using the re - injection method in the post - vascular phase showed active bleeding from a lesion close to the s5 gallbladder bed . 
 abdominal angiography was urgently performed . 
 based on ceus findings , selective cannulation of the cystic artery was performed . 
 cystic angiography findings with carbon dioxide showed extravasation . 
 he was treated by tae . 
 our case had multiple hccs , but ceus was useful for the identification of bleeding sites . 
Introduction
Case report
Discussion