Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy Antonia Valenzuela, MD,* Nghiem B. Ha, BS,* Amy Gallo, MD,w Clark Bonham, MD,w Aijaz Ahmed, MD,* Marc Melcher, MD, PhD,w Lily H. Kim, BA,* Carlos Esquivel, MD, PhD,w Waldo Concepcion, MD,w Walid S. Ayoub, MD,* Glen A. Lutchman, MD, MS,* Tami Daugherty, MD,* and Mindie H. Nguyen, MD, MAS* Goals: We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. Background: Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; how- ever, postoperative recurrence is frequently observed. Methods: This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow- up, or last visit without HCC. Results: The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P = 0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection. Conclusions: HCC recurrence rate is higher among those under- going left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence. Key Words: hepatocellular carcinoma, recurrence, hepatectomy (J Clin Gastroenterol 2015;49:158–164) H epatocellular carcinoma (HCC) is the sixth most common cancer worldwide. 1,2 Its incidence is rising in the United States, and is projected to increase in the next 2 decades. 3 Currently, there are approximately 1 million new cases annually. 4 HCC is also one of the leading causes of death globally, with an increasing incidence in the devel- oped world in the last few decades. 5 The majority of HCC patients have underlying liver disease and the presence of cirrhosis particularly will increase the risk of HCC development. 6 Among the several available treatment modalities for HCC, the only potentially curative treatments are partial hepatectomy and liver transplantation. 5 As the non- tumorous diseased liver tissue is also removed with liver transplantation, it is generally the preferred treatment modality. Partial hepatectomy is, however, often performed in transplant-eligible patients due to donor organ short- age. 7,8 With improvements in surgical techniques and per- ioperative care in the recent decades, surgical mortality is currently <5%, but long-term patient outcomes remain poor due to the high tumor recurrence rate (up to 80% at year 3 to 5). 8–11 In addition, salvage transplant is often not an option at recurrence, as tumor burden may be beyond the Milan criteria at that time. 12 Recurrent HCC can result from intrahepatic dissem- ination of the primary tumor or by de novo carcino- genesis. 13 Factors associated with recurrent HCC correlate with shorter survival. 14 Major predictors of recurrence are the presence of microvascular invasion and additional tumor besides primary lesion. 3 Nonanatomic resection has also been proposed as a predictor of recurrence but the literature is still conflicting in this regard. 15–17 To our knowledge HCC recurrence rates in patients undergoing left-sided resection versus right-sided partial hepatectomy have not been well studied. The primary objective of the current study was to determine the incidence of recurrent HCC after partial hepatectomy and to identify potential predictors of recur- rence, specifically with regard to left-sided versus right- sided resection. METHODS Study Design and Patient Population This is a retrospective cohort study of 107 consecutive HCC patients who underwent curative partial hepatectomy at the Stanford University Medical Center between January Received for publication August 23, 2013; accepted March 14, 2014. From the *Division of GI and Hepatology; and wDepartment of Sur- gery, Stanford University Medical Center, Palo Alto, CA. A.V.: study concept and design, data acquisition, data analysis, and interpretation and drafting of the manuscript. N.B.H.: study con- cept and design, data analysis and interpretation, critical review of manuscript. A.G.: study concept and design, data acquisition, data interpretation, and critical review of manuscript. C.B. and A.A.: study concept and design, data interpretation, and critical review of manuscript. M.M., C.E., W.C., T.D., W.S.A., and G.A.L.: data interpretation and critical review of manuscript. L.H.K.: data acquisition, data interpretation, and critical review of manuscript. M.H.N.: study concept and design, data acquisition, data analysis and interpretation, critical revision of the manuscript. A.V. reports been supported by a scholarship from the Chilean Gov- ernment (Becas Chile/CONICYT). The authors declare that they have nothing to disclose. Reprints: Mindie H. Nguyen, MD, MAS, 750 Welch Road, Suite 210, Palo Alto, CA 94304 (e-mail: mindiehn@stanford.edu). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE 158 | www.jcge.com J Clin Gastroenterol  Volume 49, Number 2, February 2015