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Aimee M. Crago, HMS IV Gillian Lieberman, MD March 17, 2003 Perioperative management of liver transplantation Aimee M. Crago, HMS Year IV Gillian Lieberman, MD Aimee M. Crago, HMS IV Gillian Lieberman, MD J.I. is a 66y.o. man with liver mass • The patient presented to his PCP for an annual examination and routine follow-up. • His PMH was significant for hepatitis B virus (HbsAg positive at time of presentation) and cirrhosis. • Blood tests detected elevated levels of the tumor marker AFP (24.3 compared to a normal value between 0-7). This result raised concern that the patient had developed hepatocellular carcinoma (HCC), a common sequela of cirrhosis. • The patient underwent ultrasound which demonstrated a 10cm mass in the right hepatic lobe. 2 Aimee M. Crago, HMS IV Gillian Lieberman, MD This is a classic presentation for HCC. • Chronic hepatitis B or C virus infection and cirrhosis are risk factors for the disease. • Patients such as J.I. are asymptomatic until late in the course of the disease. • Because of this fact, unless regular surveillance is performed, at time of presentation on 30% are surgically resectable. • Symptoms in advanced disease may present as – – – – – Obstructive jaundice representing bile duct obstruction Diarrhea representing malabsorption or paraneoplastic syndrome Bone pain or dyspnea reflecting metastasis Peritoneal bleed from tumor rupture Paraneoplastic syndromes (hypoglycemia, erythrocytosis, hypercalcemia, watery diarrhea, cutaneous change). 3 Aimee M. Crago, HMS IV Gillian Lieberman, MD Four main roles for imaging in this patient’s medical management I. II. III. IV. Identification and diagnosis of HCC Staging and determination of therapeutic strategy Identification of anatomical variants of import in surgical planning Post-operative surveillance and diagnosis of complications 4 Aimee M. Crago, HMS IV Gillian Lieberman, MD Differential diagnosis of a liver mass Vascular lesions • • • • • • • • Cavernous hemagioma Hemangioendothelioma Hepatocellular carcinoma Metastases Adenoma Hamartoma Hemangiosarcoma Focal nodular hyperplasia Avascular lesions • • • • • • • • • • • Cholangiocarcinoma Hepatocellular carcinoma Extrinsic mass Fatty infiltrate Hydatid cyst Liver abscess Metastases Regenerative nodular hyperplasia Polycystic disease Traumatic liver cyst Lymphoma 5 Aimee M. Crago, HMS IV Gillian Lieberman, MD I. Identification and characterization of a liver mass In context of cirrhosis, diagnosis is made by findings consistent with HCC (mass with irregular margins, heterogenous composition, hypervascularity) on two imaging modalities, one of which demonstrates hypervascularity. Aimee M. Crago, HMS IV Gillian Lieberman, MD Menu of tests to characterize a liver mass • • • • • • Ultrasound CT scan MRI Angiography (if other modalities fail to demonstrate hypervascularity) Nuclear medicine scan utilizing Tc99-labeled AFP (experimental) Histopathology under CT or ultrasound guidance (for small lesions) Biopsy of the mass is avoided unless the mass is <2cm and is unable to be adequately evaluated by non-invasive measures. This prevents possible complications related to seeding along the biopsy needle track. 7 Aimee M. Crago, HMS IV Gillian Lieberman, MD Ultrasound evaluation of a liver mass • Advantages – Readily available, low cost – Can be used intra-operatively or for screening – Can be used to evaluate vessel patency • Disadvantages – Difficult to determine identity of mass • Ultrasound appearance of hepatocellular carcinoma – Hypo-, iso-, or hyperechoic mass – Irregular echoes or margins 8 Aimee M. Crago, HMS IV Gillian Lieberman, MD US identification of hepatic mass hepatic mass – note irregular margins, heterogenic echogenicity Beth Israel-Deaconess Medical Center, PACS System 9 Aimee M. Crago, HMS IV Gillian Lieberman, MD CT evaluation of a HCC • Advantages – 90% sensitivity • Disadvantages – Does not detect lesions which are isoattenuating on non-contrast and venous phase CT – Difficulty in differentiating carcinoma from cirrhotic nodules – Reduced availability compared to ultrasound • CT appearance of hepatocellular carcinoma – Enhancing lesions observed in arterial phase of CT with contrast 10 Aimee M. Crago, HMS IV Gillian Lieberman, MD CT evaluation of HCC arterial phase venous phase hepatic mass – note mass is readily apparent in arterial phase CT, but difficult to visualize in the venous phase Kemmerer, S.R., et al. Radiol. Clin. of North America. 1998; 247-61. 11 Aimee M. Crago, HMS IV Gillian Lieberman, MD MR evaluation of a liver mass • Advantages – Improved ability to differentiate hepatocellular carcinoma and cirrhotic nodules – No nephrotoxic agents • Disadvantages – Decreased availabity versus US and CT • MR appearance of hepatocellular carcinoma – High density appearance on T2-weighted images, low density on T1weighted images. – Cirrhotic nodules appear hypodense on both T1- and T2- weighted images. 12 Aimee M. Crago, HMS IV Gillian Lieberman, MD MRI evaluation of HCC hepatic mass T1-weighted T2-weighted Beth Israel-Deaconess Medical Center, PACS System 13 Aimee M. Crago, HMS IV Gillian Lieberman, MD II. Staging and determination of therapeutic strategy Imaging studies are essential for determination of tumor resectability and for appropriate use of hepatic transplantation. Aimee M. Crago, HMS IV Gillian Lieberman, MD Treatment of hepatocellular carcinoma • Medical therapy – Systemic chemotherapy • Minimally invasive therapy – Percutaneous ethanol injection – Radioablation therapy – Trans-arterial chemoembolization • Surgical therapy – Resection – Consider transplantation if tumor is unresectable or patient has concurrent Child’s class C cirrhosis. 15 Aimee M. Crago, HMS IV Gillian Lieberman, MD Resection is performed based on the Couniard segments defined by branches of the portal vein. Meyers, W.C., et al. In: Townsend: Sabiston Textbook of General Surgery, 16th ed. pp. 997-1005. 16 Aimee M. Crago, HMS IV Gillian Lieberman, MD Contraindications to resection of HCC • Multifocal intrahepatic disease • Extrahepatic extension (local invasion of adjacent organs or visceral peritoneum) • Inadequate functional reserve (can resect less than 50% of the liver in patients with cirrhosis) • Inability to obtain adequate margins (1cm) • Involvement of confluence of hepatic/portal veins • Nodal involvement • Metastases Resectability is confirmed by intraoperative ultrasound which may change management in many cases. 17 Aimee M. Crago, HMS IV Gillian Lieberman, MD Contrandications for liver transplantation in treatment of HCC • General – Active drug or alcohol abuse – Extrahepatic malignancy – Severe heart or lung disease • HCC-specific – – – – Size of tumor >5cm Vascular invasion Metastases (CT lung and abdomen, consider bone scan) HCV infection is a relative contraindication 18 Aimee M. Crago, HMS IV Gillian Lieberman, MD Liver transplantation for HCC • Major benefit is concurrent treatment of HCC and cirrhosis therefore can be performed in patients with poor functional reserve. • Comparable 5yr. survival when compared to non-malignant causes. • Comparable outcomes as compared to resection in most studies. • HCC patients are given extra points toward severity of need as compared to others awaiting transplant. • Poor prognostic indicators include – – – – – High histologic grade Tumor >5cm Bilobar tumor Lymph node involvement Vascular invasion 19 Aimee M. Crago, HMS IV Gillian Lieberman, MD Chemoembolization of HCC is sometimes used as a bridge to transplant The protocol involves selective cannulation of the hepatic artery feeding a tumor and injection of chemotherapeutic agents (e.g., adriamycin), a contrast agent such as ethiodol, and Gelfoam which causes decrease in blood flow through the cannulated artery. common hepatic artery right hepatic artery hepatic mass branches of gastroduodenal artery Beth Israel-Deaconess Medical Center, PACS System 20 Aimee M. Crago, HMS IV Gillian Lieberman, MD Chemoembolization of HCC Ethiodolenhanced hepatic lesion – note significant reduction in size of lesion over time immediately post-chemoembolization Beth Israel-Deaconess Medical Center, PACS System 6 months post-chemoembolization 21 Aimee M. Crago, HMS IV Gillian Lieberman, MD Liver transplantation procedure Barker, C.F., et al. In: Townsend: Sabiston Textbook of General Surgery, 16th ed., 1999. pp. 429-46. 22 Aimee M. Crago, HMS IV Gillian Lieberman, MD III. Identification of anatomical variants of import in surgical planning • Pre-transplant work-up should include assessment of vascular anatomy as variants may require vessel reconstruction at the time of surgery. • Can generally be assessed by CTA or MRA • Includes evaluation for – – – – – variant hepatic artery anatomy celiac axis stenosis absent IVC thrombosis portal vein splenic artery aneurysm Aimee M. Crago, HMS IV Gillian Lieberman, MD CTA of classic arterial supply to the liver right and left hepatic arteries common hepatic artery celiac trunk proper hepatic artery Beth Israel-Deaconess Medical Center, PACS System 24 Aimee M. Crago, HMS IV Gillian Lieberman, MD Variations in the anatomy of the hepatic artery Meyers, W.C., et al. In: Townsend: Sabiston Textbook of General Surgery, 16th ed. pp. 997-1005.25 Aimee M. Crago, HMS IV Gillian Lieberman, MD IV. Post-operative surveillance and diagnosis of complications Post-operative period Late complications • • • • • • • • • • • • • Infection Post-operative bleeding Graft failure Acute rejection Biliary leak Vascular thrombosis Hepatic artery stenosis Hepatic artery pseudoaneurysm Bile duct stenosis Recurrent disease Opportunistic infection New malignancy Chronic rejection Post-operative screening performed with ultrasound at 24 to 48h after procedure and at least weekly until discharge. 26 Aimee M. Crago, HMS IV Gillian Lieberman, MD Hepatic artery thrombosis and stenosis • Clinical presentation of hepatic artery thrombosis and stenosis – – – – • Thrombosis – – – – • Elevation in LFTs Bile leaks or bile duct stricture Hepatic necrosis Relapsing septicemia Results in graft ischemia and failure Occurs in 3-12% of adult orthotopic liver transplantations Most common cause of graft loss Mortality greater than 50% if not retransplanted Stenosis – Occurs in first three months post-transplantation – 5% incidence – Sequelae similar to those of hepatic artery thrombosis 27 Aimee M. Crago, HMS IV Gillian Lieberman, MD Hepatic artery Doppler Rapid upstroke Continuous flow Resistive index = (peak systolic flow – end diastolic flow)/end diastolic flow Normal value is >0.5 and <0.8 • In HA thrombosis, see absent blood flow • In HA stenosis see prolonged upstroke with increased diastolic flow (parvis and tardus pulse) Beth Israel-Deaconess Medical Center, PACS System 28 Aimee M. Crago, HMS IV Gillian Lieberman, MD CT findings in hepatic artery thrombosis • • • • Infarction (peripheral wedge or large periportal hypodensities) Bilioma Bile duct dilitation Abscesses Hypodensity in the periportal region reflecting ischemiarelated necroses and edema Hypodense fluid collection Olliff, S. In: Grainger and Allison’s Diagnostic Radiology, 4th ed. 2001; pp. 1333-40. 29 Aimee M. Crago, HMS IV Gillian Lieberman, MD Normal angiogram Angiogram evaluation of hepatic artery patency is gold standard for diagnosis. Proper hepatic artery Hepatic artery stenosis Celiac trunk Celiac trunk Absent hepatic flow Splenic artery Right and left hepatic arteries 30 Beth Israel-Deaconess Medical Center, PACS System Aimee M. Crago, HMS IV Gillian Lieberman, MD Treatment of hepatic artery stenosis or thrombosis • Consider angioplasty or stent placement • Thrombolysis • Normally require retransplantation 31 Aimee M. Crago, HMS IV Gillian Lieberman, MD Portal vein thrombosis/stenosis • Incidence is 1-3% of orthotopic liver transplants • Treat by – – – – – percutanous angiography/stent placement thromboembolectomy venous graft placement shunt placement retransplant • US seeks to define portal vein thrombosis or stenosis as manifest by absent blood flow through the vessel. • Portal vein patency can also be visualized by CT. 32 Aimee M. Crago, HMS IV Gillian Lieberman, MD Doppler of the portal vein Normal ultrasound of the portal vein shows constant flow with minimal respiratory variation. Beth Israel-Deaconess Medical Center, PACS System 33 Aimee M. Crago, HMS IV Gillian Lieberman, MD Bile leak • Most common complication of orthotopic liver transplantation • Occurs at site of T-tube placement or bile duct anastamosis • Can reflect hepatic ischemia so must evaluate for hepatic artery patency • Hypoechoic fluid collection observed on ultrasound • Diagnosis made definitively by cholangiography with contrast placed via T-tube or percutaneous route. • Treat with observation, drainage, stent placement or surgical revision of the duct anastamosis. 34 Aimee M. Crago, HMS IV Gillian Lieberman, MD Cholangiography Contrast extravasation at the site of anastamosis between the bile duct and the duodenal Roux loop in a hepatojejunostomy reconstruction. Olliff, S. In: Grainger and Allison’s Diagnostic Radiology, 4th ed. 2001; pp. 1333-40. 35 Aimee M. Crago, HMS IV Gillian Lieberman, MD Bile duct stricture • Often due to ischemia so must rule out hepatic artery stenosis. • Other causes include – Recurrent sclerosing cholangitis – Sphincter of Oddi dysfunction – Biliary sludge/stones • Diagnosis made by observation of stricture and dilation of the bile ducts seen by US or CT and then on ERCP or MRCP. • Treat with balloon dilation or stent placement. 36 Aimee M. Crago, HMS IV Gillian Lieberman, MD ERCP Bile duct stricture Balloon dilation Bile duct postprocedure demonstrating improved patency Rerknimitr, R., et al. Gastrointestinal Endosc. 2002; 55:224-31. 37 Aimee M. Crago, HMS IV Gillian Lieberman, MD Conclusions: Role of imaging in the perioperative management of liver transplantation for HCC I. II. III. IV. Identification and diagnosis of tumor Staging and determination of therapeutic strategy Identification of anatomical variants of import in surgical planning Post-operative surveillance and diagnosis of complications 38 Aimee M. Crago, HMS IV Gillian Lieberman, MD • • • • • • • • • • • • References Barker, C.F., Brayman, K.L., Markmann, J.F., et al. Transplantation of abdominal organs. In: Townsend: Sabiston Textbook of General Surgery, 16th ed. W.B. Sauders, 1999. P. 429-46. Curley, S.A., Barnett, C.C., and Abdalla, E.K. Liver transplantation for hepatocellular carcinoma. www.UpToDate.com 2003. Ferris, J.V., Marsh, J.W., and Little, A.F. Presurgical evaluation of the liver transplant candidate. Radiologic Clinics of North America. 1995; 33:497-520. Garcia-Criado, A., Gilabert, R., et al. Radiology in liver transplantation. Semin. in US, CT, and MRI. 2002; 23:114-129. Holbert, B.L., Campbell, W.L., and Skolnik, M.L. Evaluation of the transplanted liver and postoperative complications. Radiologic Clinics of North America. 1995; 521-540. Kemmerer, S.R., Mortele, K.J., and Ros, P.R. CT scan of the liver. Radiol. Clin. of North America. 1998; 247-61. Meyers, W.C., Ricciardi, E., and Chari, R.S. Liver. In: Townsend: Sabiston Textbook of General Surgery, 16th ed. W.B. Sauders, 1999. P. 997-1005. Olliff, S. The radiology of liver transplantation. In: Grainger and Allison’s Diagnostic Radiology: A textbook of medical imaging, 4th ed. Churchill-Livingstone, 2001; pp. 1333-40. Quiroga, S., Sebastia, C., Margarit, C., et al. Complications of orthotopic liver transplantation: spectrum of findings with helical CT. Radiographics. 2001; 76:1085-102. Reeder, M.M. and Felson, B. Vascular lesions of the liver. In: Gamuts in Radiology. Audiovisual radiology of Cinncinnati, 1992. Rerknimitr, R., Sherman, S., Fogel, E., et al. Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastamosis: endoscopic findings and results of therapy. Gastrointestinal Endosc. 2002; 55:224-31. Schwartz, J.M., and Carithers, R.L. Clinical features, diagnosis, and screening for primary 39 hepatocellular carcinoma. www.UpToDate.com 2003. Aimee M. Crago, HMS IV Gillian Lieberman, MD Acknowledgements • Larry Barbaras and Cara Lyn D’amour • Gillian Lieberman, MD • Pamela Lepkowski 40