Diagnosing and Managing Cancers of the Liver and Bile Ducts Jeffrey S. Weinstein, MD Medical...

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Transcript of Diagnosing and Managing Cancers of the Liver and Bile Ducts Jeffrey S. Weinstein, MD Medical...

  • Diagnosing and Managing Cancers of the Liver and Bile Ducts

    Jeffrey S. Weinstein, MDMedical Director of Liver Transplantation Methodist Dallas Medical CenterApril 25, 2015

  • Types of Malignant Liver Tumors Metastatic tumors (most common) Hepatocellular carcinoma (HCC) Cholangiocarcinoma (CCA) Combined HCC/CCA Fibrolamellar carcinoma Hepatoblastoma Cystadenocarcinoma Epitheliod hemangioendothelioma Angiosarcoma

  • Hepatobiliary Anatomy

  • Hepatocellular (HCC)

    Clinical features Diagnostic studies Staging Treatment options Role of transplant

  • Clinical Features of HCC Usually occur in background of chronic liver disease and cirrhosis Small tumors usually cause no symptoms Larger tumors can be associated with: - abdominal pain - loss of appetite and weight loss - worsening liver function - fever - jaundice - intra-abdominal bleeding

  • Diagnostic studies for HCC Labs - AFP tumor marker Radiologic studies - Ultrasound - Multiphase MRI - Multiphase CT Biopsy

  • AFP Limitations and Uses Limitations - may be elevated with chronic hepatitis - elevated in HCC in only about ~ 40% Uses - level > 20 useful for screening but adds to costs and false positive rates - level > 400-500 about 99% specific - level > 400-500 have worse prognosis

  • Non-Invasive Radiologic Studies Used for HCC Ultrasound- screening and staging Multiphase contrast enhanced CT or MRI of abdomen and pelvis - screening, diagnosis, and staging Chest CT +/- Bone scan- staging

  • Invasive Studies Used for HCC Ultrasound or CT guided biopsy - diagnosis and staging Endoscopic ultrasound - diagnosis and staging Angiography - diagnosis and treatment

  • HCC findings on Contrast Enhanced MRI or CT Requires dedicated 4-phase study - Early and late arterial phases - Portal venous phase - Late venous phase Typical HCC - early arterial enhancement - late venous washout

  • MRI Appearance of HCCArterial phase Portal venous phase Late venous phase

  • Diagnostic Approach to HCCMass < 1cm on Ultrasound Repeat Ultrasound every 3- 6 monthsfor 2 years0rMRI/CT x 1No growthResume surveillance every 6 monthsGrowth in massContrast enhanced CT or MRITypical vs. Atypical for HCC

  • Diagnostic Approach to HCCMass < 1cm on MRI/CT Typical for HCCTreat for HCCGrowth in massRepeat MRI/CTAtypical for HCCAtypical for HCCCheck CA 19-9, biopsy or resect mass

    Monitor with U/S q 3 months

  • Diagnostic Approach to HCCMass > 1cm on MRI/CT Typical for HCCTreat for HCCObtain other study MRI/CT Atypical for HCCAtypical for HCCCheck CA 19-9, biopsy or resect mass

  • Tumor Staging for HCC Critical for determining treatment options

    Based on:

    1) Size and number of tumors2) Extension of tumor into adjacent structures3) Presence of metastases4) Severity of underlying liver disease 5) Overall physical condition of the patient

  • Staging Severity of Liver DiseaseChild Pugh Score AscitesBilirubin level Hepatic encephalopathyAlbumin level Prothrombin time/INRMELD score Prothrombin time/INRBilirubin level Serum creatinineSigns of Portal Hypertension VaricesLow platelets AscitesEnlarged spleen

  • Treatment Options for HCC Surgical resection Liver transplant (OLTx) Microwave or radiofrequency ablation Transarterial chemoembolization (TACE) Transarterial radioembolization Radiation and stereotactic radiotherapy Systemic chemotherapy Cryoablation Percutaneous alcohol ablation

  • Surgical Resection for HCC Non-cirrhotic liver or well-compensated liver disease Lesion size and location amenable to surgery Tumor confined to the liver No invasion of large vessels

  • UNOS Guidelines for OLTx & HCC Tumor < 5cm or three tumors all < 3cm Surgical resection not possible Tumor confined to liver No invasion of large vessels or lymph nodes Cirrhotic liver No other contraindications to OLTx Candidates allocated MELD score of 22 MELD upgrade every 3 months if UNOS criteria remain fulfilled

  • OLTx and HCC Bridging therapies if waiting time expected to be 6 months or more - MWA or RFA for tumors < 3 cm - TACE or Radioembolization for larger or multiple tumors About 20% will be removed from list for tumor progression before OLTx 5 year survival after OLTx ~ 75%

  • Locoregional Therapies for HCC MWA or RFA for tumors < 3cm TACE, Radioembolization and Stereotactic radiotherapy for larger or multiple tumors Tumor or tumors confined to liver Absence of severe liver dysfunction Reduce tumor burden before resection Bridging therapy before OLTx Primary treatment for those who are not candidates for surgery or OLTx

  • Systemic Therapies for HCC For advanced tumors and intact liver function Vascular endothelial growth factor inhibitors - Sorafenib* - Bevacizumab Epidermal growth factor inhibitors - Erlotinib - Cetuximab Chemotherapy - Gemcitabine + Cisplatin or Oxaliplatin - Low dose Doxorubicin or Capecitabine

  • Cholangiocarcinoma (CCA)

    Diagnostic studies Staging Treatment options Unique issues related to PSC Role of liver transplant (OLTx)

  • Anatomic Classification for CCA

    Intrahepatic 10% - arise from intrahepatic biliary tree Distal 40% - arise below the cystic duct insertion Perihilar 50% (most common in PSC) - Bismuth-Corlette classification - Klatskin tumor any involvement of hepatic duct bifurcation

  • Anatomic Classification for CCA

  • CCA and PSC

    Incidence of 0.6 to 1.5% per year Lifetime risk 5 t0 15% Younger age of onset ~ 30-50 than with CCA not associated with PSC ~ 50-70 Most tumors are perihilar 1/3 of cases diagnosed within 2 years of when PSC is first diagnosed Smoking and alcohol use may increase risk

  • When to Suspect CCA in Patients with PSC Rapid deterioration in clinical condition for those with PSC Jaundice, dark urine, pale stools, itching Dull RUQ pain Weight loss Rising Alkaline phosphatase and bilirubin Elevated CA 19-9 (> 100)

  • Diagnosing CCA

    Clinical and laboratory abnormalities Elevated tumor markers CA 19-9 Radiologic changes on MRCP, MRI/CT or PET scan Endoscopic findings on ERCP or EUS Tumor cells identified on brushings or biopsy Findings at time of Laparoscopy or Surgery

  • Studies Used to Diagnose CCA Serum tumor markers - CA 19-9 Radiologic studies - Ultrasound (U/S), MRCP, CT, MRI, and PET scans Interventional studies - ERCP and Endoscopic Ultrasound (EUS) - Percutaneous cholangiogram (PTC) - CT/MRI guided biopsies

  • CA 19-9 Limitations and Uses Limitations - cannot be detected in 5-10% of patients - may be elevated in other conditions pancreatic CA, acute cholangitis, or biliary obstruction Uses - level > 1000 correlated with advanced tumors - level > 37 useful for screening but poor specificity - level > 100-129 useful for screening or in patients with suspicious stricture - monitoring response to therapy

  • Non-Invasive Radiologic Studies Used for CCA Ultrasound +/- dopplerscreening and staging MRCPscreening, diagnosis, and staging Contrast enhanced multiphase CT or MRIdiagnosis and staging PET/CT scandiagnosis and staging

  • Radiologic Changes in PSC with Suspected CCA Stricture progression Dominant stricture Increased dilation of the biliary tree proximal to stricture Polypoid mass within the bile duct

  • Radiologic Changes in PSC with Suspected CCACCA Changes on MRCP

  • Radiologic Procedures and Interventions for CCA Percutaneous cholangiography - diagnose & stage tumor, alleviate obstruction - assess, brush, biopsy, and stent strictures - more difficult to do in PSC

    CT/MRI guided biopsies - confirm lymph node involvement with tumor - confirm suspected primary tumor* * risk of tumor seeding with biopsies

  • Endoscopic Procedures and Interventions for CCA ERCP +/- cholangiography or intraductal U/S - diagnose & stage tumor, alleviate obstruction - assess extent of tumor in and around bile duct - visualize, brush, and biopsy suspected tumors - stent obstructing tumors - has risk for infection (cholangitis) Endoscopic ultrasound - diagnose & stage tumor - assess tumor extent, regional lymph nodes and vessels - biopsy tumor* or regional lymph nodes * risk of tumor seeding when tumor biopsied

  • CCA Changes on ERCP

  • CCA on CholangiographyUlcerated strictureUlcerated and nodular stricture

  • Diagnostic Challenges Related to CCA in Patients with PSC Symptoms of PSC progression can mimic that of tumor CA 19-9 may be elevated from acute cholangitis or benign causes for impaired biliary excretion Mass lesions less common Biliary dilation proximal to point of obstruction is less common

  • Tumor Staging for CCA Critical for determining treatment options

    Based on:

    1) Extent of tumor2) Severity of underlying liver disease 3) Overall physical condition of the patient

    Laparoscopy and/or open surgery often required to complete the staging process

  • Treatment Options for Extrahepatic CCA Surgery for patients without PSC Transplant for select patients with PSC Chemoradiotherapy Systemic chemotherapy Intra-arterial chemotherapy Intra-arterial radiotherapy Photodynamic therapy

  • CCA and PSCWhats the Difference? Bile duct dama