Technical Aspects of Orthotopic Liver Transplantation for Hepatocellular Carcinoma a a,b, Lung-Yi Lee, MD , David P. Foley, MD * KEYWORDS Liver transplantation Surgery Hepatocellular carcinoma Piggyback technique Portal vein thrombosis KEY POINTS In the majority of cases, patients with cirrhosis and hepatocellular carcinoma (HCC) who undergo liver transplantation are transplanted based on their higher Model for End-Stage Liver Disease (MELD) exception score and not their physiologic MELD score; this usually results in fewer physiologic derangements during liver transplantation. Patients who have previously undergone locoregional therapy or liver resection for HCC can develop significant perihepatic adhesions that increase the complexity of the hepa- tectomy during transplant. Implantation strategy of the inferior vena cava (IVC) during liver transplant may need to be modified based on location of previously treated HCC. Patients who undergo transarterial chemoembolization for pretransplant HCC therapy may have higher rates of hepatic artery thrombosis after liver transplant; therefore, aorto- hepatic bypass grafting with donor iliac artery may be required for arterial in flow to the liver allograft. Patients with portal vein (PV) thrombosis with a bland thrombus and a patent superior mesenteric vein (SMV) can undergo successful liver transplant through either PV throm- bectomy and standard end-to-end PV-PV anastomosis, or the use of SMV-PV bypass graft with donor iliac vein. a Department of Surgery, University of Wisconsin School of Medicine and Public Health, Clinical Sciences Center, H4/766, 600 Highland Avenue, Madison, WI 53792-3284, USA; b Veterans Administration Surgical Services, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA * Corresponding author. Clinical Science Center, H4/766, 600 Highland Avenue, Madison, WI 53792-7375. E-mail address: [email protected] Surg Clin N Am 96 (2016) 269–281 http://dx.doi.org/10.1016/j.suc.2015.11.004 surgical.theclinics.com 0039-6109/16/$ – see front matter Published by Elsevier Inc. 270 Lee & Foley INTRODUCTION Hepatocellular carcinoma (HCC) remains a significant worldwide malignancy. Liver cancer, primarily HCC, is the fifth most common cancer in men, the ninth most com- mon cancer in women, and the second leading cause of cancer death in the world.1 In the United States, HCC ranks tenth in new estimated cancers but represents the fifth leading cause of cancer death.2 Most cases of HCC develop in the setting of cirrhosis secondary to viral hepatitis (hepatitis B virus [HBV] and hepatitis C virus [HCV]) and alcohol overuse.3 However, there has been a rising association between obesity, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and HCC.4,5 In fact, more reports have described an increased incidence of HCC in noncirrhotic patients with NAFLD or nonalcoholic steatohepatitis (NASH).6 Due to the ongoing obesity epidemic, it is likely that the incidence of NAFLD and NASH will increase, as will the presence of HCC in these patients. There are multiple therapies aimed at treating patients with HCC. Locoregional ther- apies for HCC include radiofrequency ablation,7 microwave ablation,8 cryotherapy,9 transarterial embolization,10 and radioembolization.11 The decision to use a specific therapy is based on multiple factors, including but not limited to tumor size, biology, location, and number, as well as institutional expertise. Surgical resection of HCC can be a viable option for patients with compensated hepatic function.12 The decision to perform resection is based upon the location of the tumor, absence of macrovas- cular invasion and extrahepatic disease, size of the remnant liver, severity of portal hy- pertension, and the lack of significant comorbidities. Patients who are not candidates for surgical resection can be considered candi- dates for liver transplantation. However, careful selection of the appropriate candidate is critical for obtaining optimal outcomes after transplantation. This article discusses the selection of candidates with HCC for liver transplantation and the technical as- pects of orthotopic liver transplantation for HCC. PATIENT SELECTION All patients with cirrhosis who are evaluated for liver transplantation undergo an extensive workup to be sure that they can tolerate the complexities of the surgical procedure. Some of these tests include, but are not limited to, noninvasive cardiac stress test, cardiac catheterization, 2-dimensional echocardiogram, and abdominal imaging to assess the hepatic vascular anatomy and the presence of tumors. When a diagnosis of HCC is made, the Milan criteria are used to determine which pa- tients with HCC are suitable candidates for liver transplantation. The Milan criteria were established from a prospective study performed by Mazzaferro and col- leagues13 in 1996. In this report, the eligibility criteria for transplantation were the presence of a tumor 5 cm or less in diameter in patients with a single HCC, and no more than 3 tumor nodules each 3 cm or less in diameter in patients with multiple tu- mors. Recipients who met these criteria had overall and tumor-free 4-year survival rates of 85% and 92%, while patients with greater tumor burden had survival rates of 50% and 59%, respectively. Because these survival rates were similar to those in liver transplant recipients without HCC, the Milan criteria became and have remained the standard tumor accep- tance criteria for patients with HCC undergoing liver transplantation. However, in the past, some had felt that the Milan criteria were too restrictive, meaning that that pa- tients with tumor burden outside Milan criteria may be suitable for liver transplantation. In 2001, Yao and colleagues14 established the University of San Francisco (UCSF) criteria by studying patients with expanded criteria. These criteria included single Transplantation for Hepatocellular Carcinoma 271 tumors of no more than 6.5 cm or no more than 3 tumors, with each tumor being no more than 4.5 cm, with a sum tumor diameter of no more than 8 cm. When these pa- tients were transplanted, their 5-year survival after liver transplantation was 75%. These data suggested that the selection of patients with tumor burden that is outside Milan criteria but within UCSF criteria may have acceptable outcomes after liver transplantation. Despite these favorable results in patients within UCSF criteria, the allocation of deceased donor livers for patients with HCC depends upon the Model for End-Stage Liver Disease (MELD) score and the Milan criteria. The MELD scoring system was imple- mented in 2003 as a predictor of mortality for patients on the liver transplant waiting list. The physiologic MELD score is based on the patient’s creatinine, total bilirubin, and in- ternational normalized ratio (INR), and it is predictive of 90-day waitlist mortality.15 In many cases, patients with HCC have compensated liver function with low physiologic MELD scores, and they are less likely to be transplanted in a timely manner. If liver allo- cation were solely based on their physiologic scores, there would be a high likelihood of tumor growth outside of Milan criteria, thus making the patient ineligible for liver trans- plant. In order to create equipoise for these patients on the list, MELD exception scores are given to HCC patients to increase their likelihood of being transplanted. With the implementation of MELD exception points for patients with HCC, there has been an increase in the number of patients transplanted with HCC exception scores over time. According to the most recent Scientific Registry for Transplant Recipients Annual Report, the number of liver transplants per 100 wait-list years performed in 2012 was three times higher among active adult candidates with HCC exceptions compared with those candidates without HCC exceptions.16 In most instances, wait-listed patients with cirrhosis and HCC have MELD exception scores that are higher than their physiologic MELD scores. Therefore, these exception scores become their allocation scores. From a technical standpoint, liver transplantation is generally less complicated for patients with HCC due to the fact that they are usually receiving livers based on their MELD exception scores that are higher than their physiologic MELD scores. Because of compensated liver function in most of these patients, the authors have generally observed less coagulopathy, reduced portal hypertension, and preserved renal func- tion during liver transplant. For these reasons, the hepatectomy and liver transplant are usually more straightforward. However, there are exceptions in these patients that can make the liver transplant in the setting of HCC more technically challenging. This article will discuss the technical aspects of orthotopic liver transplantation for pa- tients with cirrhosis and HCC. SURGICAL TECHNIQUE Preoperative Planning If patients with HCC do not have a potential living donor, they can be placed on the deceased donor waiting list. If their tumor burden is initially within Milan criteria and remains there for 6 months, they receive a MELD exception score of 28. As long as they remain within Milan criteria, they receive a 10% increase for each subsequent 3-month interval until their score is capped at 34. Patients who are within UCSF criteria are not eligible for an automatic exception score but can be downstaged into Milan criteria with locoregional therapy. A recent analysis revealed that successful