1. Exophytic hepatocellular carcinoma

2. Exophytic hepatocellular carcinoma ?
Pedunculated hepatocellular carcinoma ?

3. Pathology of hepatocellular carcinoma, Masamichi Kojiro 2006
Gross classification
Three major types
Nodular, massive, diffuse by Eggel’s classifcation
Nodular
Single or multiple nodular tumors with clear demarcation
Massive type
Large tumor with an irregular boundary
Occupies almost an entire right or left lobe
Nodular type grows extensively and occupies an entire lobe -> massive type
Diffuse type
Diffuse proliferation of numerous minute tumor nodules throughout the entire lobe or liver
Mimic LC
Pathology of hepatocellular carcinoma, Masamichi Kojiro 2006

4. Subclassification of Nodular type Simple nodular type
Nodular and well demarcated
Surrounded by a distinct fibrous capsule
Grossly, extranodular tumor growth, intrahepatic metastasis, and/or vascular invaion (-)
Simple nodular type with extranodular growth
Extranodular growth beyond the capsule
Vascular invasion, small metastasis
Confluent multinodular type
Joining together of a few to numerous small tumor nodules
Portal tracts entrapped
Vascular invasion higher

5. Unusual gross types Pedunculated HCC
Extrahepatic tumor growth with or without peduncle
In the narrow sense, only HCC growging extrahepatically with a peduncle can be called
Spherical lesion without a peduncle – protruded-type HCC
Most – originates from the accessory lobe of the liver and/or heterotropic liver

6. Pedunculated HCC P-HCC
carcinoma protruding from the liver with or without a peduncle
carcinomatous invasion of the liver is slight
P-HCCs constitute 0.24% % of all HCCs in Japan
World J. Surg. Vol. 26, No. 9, September 2002

7. Clinical features of P-HCC
From 1986 to 1998
the clinical features of 18 surgically treated cases
including demographics, laboratory data, operative findings, pathologic features, and follow-up results.
414 patients with nonpedunculated hepatocellular (HCC) vs 18 patients with p-HCC
P-HCC
Larger tumor size, more capsule formation, less vascular invasion(d/t capsular formation), and wider resection margins
The 1-, 3-, and 5-year survival rates of P-HCC patients were 88.3%, 77.4%, and 45.6%, respectively.
P-HCC patients without vascular invasion might have a significantly better survival
World J. Surg. Vol. 26, No. 9, September 2002

8. Image findings On dynamic CT, an intraductal HCC
shows high density during hepatic arterial phase
washout during portal venous phase.
⇒ typical enhancement pattern of HCC, surrounding cirrhotic liver, and bile duct dilatation by the mass may be clues for the diagnosis of an exophytic HCC.
Korean J Radiol 9(1), February 2008

9. Retroperitoneal extension → mimic a right adrenal tumor
Exophytic growth of HCCs may be seen in any lobe or segment of the liver
Duodenal invasion, mimic a duodenal GIST
Bile duct and portal vein invasion
late presentations in usual intrahepatic HCCs and they may be seen in exophytic HCCs
Contiguous with a bile duct mass is a similar finding to a usual intrahepatic HCC with bile duct invasion, except for location
Korean J Radiol 9(1), February 2008

10. Prognosis of P-HCC Between 1983 and 1995
13 patients (3.4%) of 380 patients at Tottori univ. hospital patients reported previously
Macroscopically
P-HCC with pedicle and without pedicle attached in the liver surface
Surgically treated patients > TACE or TAI
P-HCC histologically moderately or poorly differentiated
Unfavorable prognosis, rapid progressive nature
Early diagnosis, early surgical resection
Oncology 1999:57;23-28

11. Treatment Gut 2003;52(Suppl III):iii1–iii8
Tumor status, Liver function, General condition
TNM classification
Tumor size, number of tumor nodules, involvement, vascular invasion, invasion of major branch of portal or hepatic veins, regional lymph node metastasis, and distant metastasis
Small HCC (< 5cm) with child A or compensated liver function → Resection
Localized HCC (>5cm) with child A or compensated liver function → Resection
For unresectable localized HCC → cytoreduction and sequential resection
Regional radiotherapy can be added
For multiple HCC → TACE
TACE can still be tried in individual patients who had tumor thrombus in the main portal vein when collateral circulation is good and liver function acceptable.
For HCC with Child C cirrhosis, only symptomatic treatment
Gut 2003;52(Suppl III):iii1–iii8

12. Surgical resection
Liver transplantation
Radiofrequency ablation (RFA)
Percutaneous ethanol or acetic acid ablation
Transarterial chemoembolization (TACE)
Cryoablation
Radiation therapy
Systemic chemotherapy

13. Surgical resection
Potentially curative partial hepatectomy is the optimal treatment for HCC.
Patients ideally suited for resection
a solitary HCC confined to the liver
no radiographic evidence of invasion of the hepatic vasculature
no evidence of portal hypertension
well-preserved hepatic function.

15. Design : Retrospective study of a multi-institutional database.
Hypothesis
Hepatocellular carcinoma (HCC) ≥ 10 cm may benefit from hepatic resection.
Design : Retrospective study of a multi-institutional database.
Patients :
300 patients who underwent hepatic resection for ≥ HCC 10 cm
Results
The perioperative mortality rate was 5%. At a median follow-up of 32 months, the median survival was 20.3 months, and the 5-year actuarial survival rate was 27%.
Poor survival : 4 clinical factors-alpha-fetoprotein of 1000 ng/mL or higher, multiple tumor nodules, the presence of major vascular invasion, and the presence of severe fibrosis
Clinical score according to the following risk factors: 1, no factor; 2, one or two factors; or 3, three or four factors.
Conclusions : Large HCCs should be considered for liver resection as this treatment is associated with a 5-year survival rate exceeding 25%. Clinical predictors should not be used to exclude patients from surgical resection because these factors do not reliably predict outcome.
Arch Surg 2005 May;140(5):450-7; discussion 457-8

16. Radiofrequency ablation
Percutaneous RFA is superior to PEI
Frist choice of treatment modality
there is no absolute tumor size
2.5cm or smaller : completely ablated
3cm : Generally indicated
>3cm : combined with TACE
Local residual and microsatellite lesions and residual microvascular invasion
For cirrhotic patients, Child-Pugh class A or B
Contraindications : jaundice, refractory ascities, a bleeding tendency, <50,000/mm plt
Relative contraindications : close to the stomach and intestine, gallbladder, and bile duct and the heart
Oncology 2010:78(suppl 1):

17. The Japan Society of Hepatology (JSH)
RFA + TACE : >3cm
4 or more nodules – RFA
Child-Pugh C HCC without refractory ascites, bilirubin 3mg/ml or lower
Europe and North America, American Association of the Study of the Liver Disease (AASLD)
≤ 3cm early-stage HCCs
≤ 2cm very-early-stage HCCs with complications – portal HTN
Large HCC
Recurrence rate↑
⇒ Lipiodol TACE-precended RFA
Oncology 2010:78(suppl 1):

18. Lesions Proximal to the Hepatic Portal Glisson’s Capsule
Rt. Subdiaphragmitic lesion and located the intraabdominal free surface
“artificial ascites method”
5% glucose solution or normal saline infused into the intrapleural or intraabdominal cavity as artificial pleural effusion or peritoneal fluid
Lesions Proximal to the Hepatic Portal Glisson’s Capsule
Large tumor – in the hepatic portal region
Ethanol injection can be performed
Endoscopic nasobiliary drainage tube is inserted into the bile duct → cooling by the perfusion of ice-cold water → markedly reduced bile duct injury
Lesions in the Caudate lobe
Many vessels when adopting a right intercostal approach
Penetrates into the intraaabdominal cavity in a left lobe approch
⇒ laparoscopic surgery
Oncology 2010:78(suppl 1):

19. For inhibiting recurrence after RFA
Interferon
Sorafenib : STORM trial, underway
Resection 후 RFA
Ablation by retinoid
Oncology 2010:78(suppl 1):

20. Prev. studies : higher local recurrence rate in subcapsular group
unifocal subcapsular hepatocellular carcinoma (HCC) vs nonsubcapsular tumors
Prev. studies : higher local recurrence rate in subcapsular group
A total of 42 patients with unifocal HCC underwent percutaneous radiofrequency ablation
between May 1998 and August Subcapsular tumors were selected
they were ablated through an indirect puncture, a gradual increase in radiofrequency power output, and needle track ablation.
Radiofrequency ablation of subcapsular HCC can be comparable to that of nonsubcapsular HCC
Proper case selection, indirect puncture of the index tumor, a gradual increase in power deposition, thermocoagulation of th e needle track
AJR:190, April 2008,

21. Transarterial chemoembolization
Injection of a chemotherapeutic agent, with or without lipiodol or a procoagulant material, into the hepatic artery
Lipiodol
oily contrast agent
promotes intratumoral retention of chemotherapy drugs
Most often for large unresectable HCCs
Bland particle embolization alone (ie, without chemotherapy) has also been used for both unresectable and locally recurrent HCC

22. Absolute contraindications
absence of hepatoportal blood flow (portal vein thrombosis)
encephalopathy
biliary obstruction
Relative contraindications
Serum bilirubin >2 mg/dL
Lactate dehydrogenase >425 unit/L
Aspartate aminotransferase >100 unit/L
Tumor burden involving >50 percent of the liver
Cardiac or renal insufficiency
Ascites, recent variceal bleed, or significant thrombocytopenia

23. Spontaneous rupture The causes Predisposing factors an uncommon
potentially life-threatening presentation with distinct geographic differences.
The causes
tumor and capsular necrosis with secondary infection
vascular injury during TACE
from inflammation secondary to the chemotherapeutic agents
Predisposing factors
large tumor size
extracapsular extension
the male sex
exophytic growth of tumor
Korean J Radiol 9(1), February 2008

24. Extrahepatic collateral arteries
Tumors are large or peripherally located
Exophytic
Interferes with effective control of the tumor with TACE
Causes of extrahepatic collateral vessel formation
Hepatic artery occlusion by surgical ligation
Hepatic artery interruption by repeated TACE or arterial dissection
The anatomic location of the tumor adjacent to the bare area and suspensory ligaments of the liver and direct invasion of or adhesions to adjacent organs
RadioGraphics 2005:25:S25-S39

26. Collateral vessels are chemoembolized
-> embolizing nontarget brandches → Selective catheterization should be achieved
Embolic materials should be infused incrementally to prevent embolic materials from refluxing into a nontarget branch
Coils and gelatin sponge particles may be used to occlude and protect the territory of the normal distal branches before chemoembolization
To reduce shoulder pain → 1% lidocaine be injected intraarterially
Both the hepatic artery and extrahepatic collateral vessels
supply a tumor
Additional extrahepatic collateral vessel chemoembolization should be attempted to increase the therapeutic efficacy of TACE for hepatocellular carcinoma.

27. Cryoablation unresectable HCC unapproachable by RFA in cases
alternating freeze thaw cycles through the use of a cryoprobe inserted directly into the tumor

28. Percutaneous ethanol or acetic acid ablation
Small HCCs who are not candidates for resection due to their poor functional hepatic reserve
acetic acid, which may have fewer side effects than ethanol

29. Radiation therapy The place of external beam radiation therapy (RT)
unresectable HCC has yet to be defined
HCC is a radiosensitive tumor
the liver can only tolerate about 20 Gy
Stereotactic radiotherapy — Stereotactic body radiation therapy (SBRT)
high dose radiation fractions are delivered to a small, precisely-defined target by using multiple, non-parallel radiation beams
small or moderated sized tumors in extracranial sites in either a single or limited number of dose fractions

30. Selective internal irradiation
An alternative means of delivering focal radiation employs radioactive isotopes
iodine-131 [131I]- labeled lipiodol or yttrium-90 [90Y]-tagged glass microspheres)
delivered selectively to the tumor via the hepatic artery

31. Case I A 68-year-old man with HBV-related cirrhosis
Sonographic and CT scan
a 17 cm × 14 cm × 10 cm tumor between left hepatic lobe and spleen, which also involved the upper pole of spleen and almost made no invasion into the liver
Celiac and hepatic arteriography displayed mass lesions taking blood from left hepatic artery, splenic artery and left inferior phrenic artery, and transarterial chemoembolization was performed
Image-guided biopsy of tumor was consistent with HCC.
He underwent spleen, tumor and partial left hepatic lobe resection in January 2008.
A negative follow-up for clinical and radiological investigation at 17 mo after surgery.
World J Gastroenterol 2009 November 7; 15(41):

33. Case II A 50-year-old woman Hepatitis B virus positive May 2000
Rt. Hemihepatectomy
Initial tumor : Segment V, 10cm in diameter with capsule invasion
Moderately differentiated HCC
January 2001
Partial resection of medial segment d/t recurrence in the form of intrahepatic metastasis
8 years f/u -> No recurrence
Journal of Oncology 2009;2009:231854

34. December 2008 January 2009 The recurrence from the remnant liver
CT : heterogenous mass, 9X7cm
Expanded to the adjacent organs, IVC, pericardium
The markedly extrahepatic growth formation and feeding routs depending on IPA and IMA
TACE 시행
January 2009
Complete surgical resection
Secondary metastases in the lung or bone

36. Case III
four patients
a laparoscopic resection for completely exophytic HCC on cirrhosis
located in segment IV (2) and in segment III and segment V
limited laparoscopic liver resections could be considered to be the best option for the treatment of extremely rare protruding HCC on cirrhosis
Indications
Well compensated cirrhosis (Child A or B < 3), having lesions of 5 cm or less
located in the left or peripheral right segments (segments II–VI of Couinaud’s classification).
Contraindications
Large tumors (deeply sited or located in the superior and posterior segments) and lesions close to the portal bifurcation or close to the suprahepatic junction
J Hepatobiliary Pancreat Surg 2005:12:488–493

37. Case IV A 79-year-old female Diarrhea, asthenia, weight loss
Abdomen CT : a large liver mass with exophytic growth towards the right iliac fossa
FNA : well differentiated HCC
Chemoembolization
Asymptomatic after 6 months of F/U
정확한 TACE 방법은 기술 (-)
Spanish journal of gastroenterology 2008, 100,

38. Conclusions Resectability 판단
Well demarcated, P-HCC c peduncle without invasion to adjacent organs : Surgical resection
Large or large exophytic HCC : TACE + RFA
TACE
Check extrahepatic arterial supply
Rupture