Focal liver lesion

Liver TumorsDr Rajendra DesaiMS, DNB, MCh (GI Surgery), FRCSDept of General SurgeryShadan Institute of Medical SciencesWORKUP ALGORITHM FOR LIVER MASS

HistorySymptoms - abdominal pain/ pressure effect,fever,anorexia,weight loss

Patient characteristics (age, gender, use of OCP, risk factors for chronic liver disease )

History or findings of extra-hepatic malignancyPhysical examination and investigationSign of chronic liver stigmata or portal hypertentionLymphadenopathyCBC with PLT , coagulogram , LFT , hepatitis profile , tumor markerUltrasound , CT scan , MRI

Study show accurate preoperative evaluation of liver mass lesions without fine-needle biopsy about 98% by history and lab (including tumor markers) and a variety of imaging studies

Fine needle biopsycommonly used to assist in the diagnosis of a variety of liver lesionsDisadvantageIncrease risk of bleeding and seeding of neoplastic cellsSome type liver lesion cannot diagnosis such as hepatic adenomas and focal nodular hyperplasia MalignancyMetastatic liver tumors HCCCholangiocarcinoma Rare tumor hepatoblastoma , Germ cell tumor , Angiosarcoma , non-Hodgkin lymphoma

Metastatic liver tumors Most common metastasis malignant hepatic neoplasmThe most common primaries : breast, lung, colon

History or findings of extrahepatic malignancy menifestation

U/S multiple and hypoechoic lesion with Hypoechoic rims and internal heterogeneityCT Hypovascular or hypervascular mass depend on metastasis originMRI metastatic lesions appear as low signal areas on T1-weighted images and moderately high signal on T2-weighted images

Hepatocellular CarcinomaEpidemiologyHepatocellular carcinoma is the 5th most common malignancy worldwide & the 3rd cause of cancer related death with male-to-female ratio5:1 in Asia2:1 in the United States Tumor incidence varies significantly, depending on geographical location.

HCC with age. 53 years in Asia67 years in the United States.

135-year survival less than 10%Maximum increase in obesityIncidence of HCC

EtiologyHepatitis B-increase risk 100 -200 fold- 90% of HCC are positive for (HBs Ag)Hepatitis CCirrhosis- 70% of HCC arise on top of cirrhosisToxins -Alcohol -Tobacco - AflatoxinsAutoimmune hepatitisStates of insulin resistance- Overweight in males Diabetes mellitus

15Incidence according to etiology

Abbreviations: WD, Wilsons disease; PBC, primary biliary cirrhosis, HH, hereditary hemochromatosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection.Signs & symptomsNonspecific symptoms abdominal pain Fever, chills anorexia, weight loss jaundice

Physical findings abdominal mass in one third splenomegaly ascites abdominal tenderness

17Guidlines(a) which patients are at high risk for the development of HCC and should be offered surveillance(b) what investigations are required to make a definitediagnosis (c) which treatment modality is most appropriate in a given clinical context.

18Guidlines- M &F with established cirrhosis due to HBV and/ or HCV, particularly those with ongoing viral replication

- M &F with established cirrhosis due to genetic haemochromatosis

- M with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment

- M with primary biliary cirrhosis

Abdominal US and AFP/ 6 months(a) which patients are at high risk for the development of HCC & should be offered surveillance19Diagnosis(b) what investigations are required to make a definite diagnosis

AFP produced by 70% of HCC> 400ng/ml AFP over time

2) Imaging- focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC

- Spiral CT of the liver

- MRI with contrast enhancement20

Hepatocellular carcinoma, CT of the liver before (a) and 15 sec (b), 45 sec (c) and 90 sec (d), respectively, following intravenous contrast medium administrationDiagnosis3) Biopsy is rarely required for diagnosis in 13%. Biopsy of potentially operable lesions should be avoided where possibleseeding22DiagnosisCirrhosis +Mass > 2 cmRaised AFPNormal AFPConfirmed diagnosisCT, MRI23DiagnosisCirrhosis + Mass < 2 cmRaised AFPNormal AFPAssess for surgeryCT, MRI lesion by examFNAC or biopsy Confirmed diagnosis24Treatment (Surgery)The only proven potentially curative therapy for HCC Hepatic resection or liver transplantation

Patients with single small HCC (5 cm) or up to three lesions 3 cm

Involvement of large vessels (portal vein, Inferior vena cava) doesnt automatically militate against a resection; especially in fibrolamellar histology

No randomised controlled trials comparing the outcome of surgical resection and liver transplantation for HCC.

Treatment (Surgery)Hepatic resection should be considered in HCC and a non-cirrhotic liver (including fibrolamellar variant)

Resection can be carried out in highly selected patients with cirrhosis and well preserved hepatic function (Child-Pugh A) who are unsuitable for liver transplantation. It carries a high risk of postoperative decompensation.

Perioperative mortality in experienced centres remains between 6% and 20% depending on the extent of the resection and the severity of preoperative liver impairment.

The majority of early mortality is due to liver failure.

Treatment (Surgery)Recurrence rates of 5060% after 5 years after resection are usual (intrahepatic)

Liver transplantation should be considered in any patient with cirrhosis

Patients with replicating HBV/ HCV had a worse outlook due to recurrence and were previously not considered candidates for transplantation.

Effective antiviral therapy is now available and patients with small HCC, should be assessed for transplantation

Treatment (non-Surgical)should only be used where surgical therapy is not possible.

Percutaneous ethanol injection (PEI) has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3 cm in diameter

Radiofrequency ablation (RFA)High frequency ultrasound to generate heatgood alternative ablative therapy No survival advantageUseful for tumor control in patients awaiting liver transplant

Treatment (non-Surgical)3) Cryotherapyintraoperatively to ablate small solitary tumors outside a planned resection in patients with bilobar disease

4) Chemoembolisation Concurrent administration of hepatic arterial chemotherapy (doxirubicin) with embolization of hepatic arteryProduce tumour necrosis in 50% of patientsEffective therapy for pain or bleeding from HCCAffect survival in highly selected patients with good liver reserveComplications: (pain, fever and hepatic decompensation)Treatment (non-Surgical)5) Systemic chemotherapy very limited role in the treatment of HCC with poor esponse rate Best single agent is doxorubicin (RR: 10- 20%)Combination chemotherapy didnt response but survivalshould only be offered in the context of clinical trials

6) Hormonal therapyNolvadex, stilbestrol and flutamide

7) Interferon-alfa8) retinoids and adaptive immunotherapy (adjuvant)

Selection of agents for targeted therapy in HCCNameTargetGefitinibErlotinibLapatanibCetuximabBevacizumabSorafenib (Nexavar) Sunitinib VatalanibCediranibRapamycinEverolimusBortezomib (Velcade) EGFREGFREGFREGFRVEGFRaf1, B-Raf, VEGFR , PDGFRPDGFR, VEGFR, c-KIT, FLT-3VEGFR, PDGFR, c-KITVEGFRmTOR (mammalian target of rapamycin)mTORProteasomeTargeting angiogenesis for HCCHCC is one of the most vascular tumorMajor driver of angiogenesis is vascular endothelial growth factor (VEGF)Sorafenib and bevacezumab target VEGF in HCC

Bevacizumzb: Median OS of approximately 12 monthsBevacizumab + erlotinib: Medain OS 15-17 months

32HCC (Whats ahead?)Combinations therapy

Bevacizumzb or Sorafenib + ErlotinibSorafenib + mTOR inhibitor

Early sequential therapies

Fibrolamellar hepatocellular carcinoma (FCHC)FHCC is a rare form ofhepatocellular Approximately 200 new cases are diagnosed worldwide each year.FHCC often does not produceAFP However, FHCC is elevatedNeurotensin and Vitamin B12 Binding protein levels.FHCC generally occurs in young adults without underlyingcirrhosis.FHCC grows slowly and has better prognosis, Fibrolamellar hepatocellular carcinoma (FCHC)The histopathology of FHCC is characterized by laminated fibrous layers, interspersed between the tumor cells.FHCC has a highresectability rate

Hepatoblastomamost common liver cancer in childrenmost commonly diagnosed during a child's first three years of lifeusually present with an abdominal massPatients with familial adenomatous polyposis (FAP) are risk factorOften elevated AFPTreatment : Surgicalresection,adjuvant CMT, andliver transplantation

Germ cell tumorGerm cell tumor is a neoplasm derived from germ cells.can be cancerous or non-cancerous ClassificationGerminomatous or seminomatousNon-germinomatous or non-seminomatous

CholangiocarcinomaIt has an annualincidencerate of 12 cases per 100,000 in the Western worldrates of cholangiocarcinoma have been rising worldwide over the past several decades.CholangiocarcinomaIt may be suspected in a patient withobstructive jaundice. CT scanning is an important role in the diagnosis of cholangiocarcinoma.may be challenging in patients with primary sclerosing cholangitis (PSC)ERCP advantages include the ability to obtainbiopsiesand to place stentsor perform other interventions to relieve biliary obstruction.Benign HemangiomasFocal nodular hyperplasiahepatic adenomasSimple cystsHemangiomasMost common benign liver tumorsFemale : male > 3 : 1Most are asymptomatic and no malignant transformationLarge hemangiomas can cause symptoms as a result of compression of adjacent organs or intermittent thrombosisSurgery may be considered an option if the patient is symptomaticGross : round pink or red capsule

HemangiomasU/Sechogenic spot, well demarcatedCT scan Early phase hypodense peripheral enhancement Delay phase contrast fillling mass MRI High sens and spec , high acurracy Hyperdense in T2 and blood fill space

Peripheral nodular enhancement follow by gradual centripetal enhancement

Focal nodular hyperplasia

Most commonly in women and asymptomaticNo malignant transformationGross : subcapsular lesion and central scarSurgery indicate in symptomatic patient

Focal nodular hyperplasiaU/S Nodule with varying echogenicityCT scanNon contrast phase low density masscontrast phase rapid enhance and wash out with central scarMRI Hyperdense and central scar

HomogeneousIsoattenuationImmediate Intense enhancement

Central scar 2/3FNH & Hemangioma

Symptomatic : Surgery Hepatic Adenomas

Benign epithelial liver tumor that usually occurs in non-cirrhotic livermost commonly seen in premenopausal women older than 30 years of age and relate with oral contraceptives useAbout 50 % abdominal pain and 30 % bleedingRisk of malignant transformation 10%Surgery indicate in mass > 4 cm , no decrease size when stop pill

hepatic adenomasU/S often large and in the right lobe of the liver and hyperechoic lesionCT scanNon-contrast scan well-demarcated low density massContrast-enhanced scans Rapid enhance and wash out same FNHNo central scar difference from FNHHA

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