INTRODUCTION

Liver cancer is the sixth most common cancer and, in 2018, was the fourth leading cause of cancer-related death worldwide. The rates of incidence and mortality are approximately 2 to 3 times higher for men than for women. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for 75% to 85% of diagnoses, followed by intrahepatic cholangiocarcinoma (10%–15%), and other rare liver histologies. The improvement and safety of surgical techniques for liver resection and transplant, and advancements in ablation, transarterial chemoembolization (TACE), and systemic therapies have expanded the treatment options for patients with HCC. Liver transplant is the ideal treatment option for patients with HCC and poorly compensated liver disease because it removes both HCC and damaged liver and reduces the risk for early recurrence. However, shortages in donor liver and long waiting times to transplant are significant barriers to this treatment approach. As such, liver resection remains an effective treatment option for patients with HCC. The use of a multidisciplinary approach and the knowledge of each therapeutic option is critical in the management of patients with HCC.

SURGICAL RESECTION

Minimal future liver remnant requirements
Liver resection remains the treatment of choice for HCC. Two major preoperative considerations for HCC resection are the patient’s liver function and the predicted future liver remnant (FLR). The intrinsic liver function of patients with HCC is often impaired because this patient population generally has chronic liver disease, including viral hepatitis, alcoholic hepatitis, and nonalcoholic steatohepatitis. As such, studies report that more FLR is needed for patients undergoing resection for HCC than for patients undergoing resection of secondary liver cancer (ie, metastatic disease). The minimal requirement of FLR/standardized liver volume (standardized liver volume 5 x 794 1 1267.28 x body surface area) is 30% in patients with hepatic injury and fibrosis and 40% in patients with cirrhosis, whereas it is 20% to 25% for patients with normal liver.

Anatomic resection versus nonanatomic resection
Anatomic resection of Couinaud segment for small HCC was reported in 1981 by Makuuchi and colleagues. HCC frequently invades to the intrahepatic vascular structures and spreads through the portal vein. As such, the complete removal of tumor-bearing portal territory was reported to be theoretically superior to nonanatomic resection. The technique proposed by Makuuchi and colleagues is detailed as follows: (1) under the guidance of intraoperative ultrasonography, the portal vein of interest is identified and punctured using a 22-gauge needle; (2) blue dye is injected into the portal vein; (3) the territory of the dyed surface is marked using electrocautery; and (4) liver resection is performed using ultrasonography guidance and intersegmental hepatic veins are exposed. This technique was recently refined using fluorescence imaging. By using transportal injection or systemic intravenous injection of indocyanine green, the portal vein territory was more clearly visualized on the liver surface compared with the traditional method. Many retrospective studies reported that anatomic resection was associated with better survival and lower recurrence than nonanatomic resection. In contrast, other studies showed that survival did not differ significantly between patients undergoing anatomic resection and those undergoing nonanatomic resection. Therefore, this clinical question remains unanswered and needs to be further elucidated.

Laparoscopic liver resection
Laparoscopic liver resection (LLR) has been increasingly used worldwide. In their systemic review, Nguyen and colleagues reported on the safety of LLR with low rates of morbidity and mortality for both major and minor resections, as well as appropriate oncologic results compared with open liver resection (OLR). These results are most likely caused by patient selection and the advantages of the laparoscopic approach, including a magnified view and the hemostatic effect caused by pneumoperitoneum. Three retrospective studies including more than 200 patients showed that the 5-year overall survival (OS) was not significantly different between patients undergoing LLR for HCC and those undergoing OLR for HCC. However, no randomized controlled trials (RCTs) comparing long-term outcomes in patients undergoing LLR versus OLR for HCC have been reported. For patients with colorectal liver metastases, a recent RCT (Oslo-CoMet study) showed that median OS in patients undergoing LLR was similar to those undergoing OLR: 80 months versus 81 months.

Liver Resection Versus Ablation
It remains unclear whether liver resection or ablation is the most effective treatment of small HCC lesions. To answer this clinical question, 5 RCTs have been reported. Two of these studies showed that liver resection was associated with better survival than radiofrequency ablation and 3 showed that survival did not differ significantly between patients undergoing resection and those undergoing ablation. The shortcomings of these RCTs include insufficient patient follow-up; unclear treatment allocation; and different inclusion criteria, including tumor number, tumor diameter, and Child-Pugh grade. Nonetheless, for patients with small HCCs (ie,<3 cm), the current evidence shows that both resection and ablation can be recommended.

Liver Resection Versus Transarterial Chemoembolization
There has been 1 RCT comparing the outcomes of patients undergoing resection for HCC with those undergoing TACE. For patients outside of Milan criteria, resection was associated with better survival than TACE. The authors found 8 cohort studies comparing outcomes after resection with TACE using the propensity score adjustment. Although the studies had different inclusion criteria, the data show that resection is associated with better survival than TACE in selected patients who have multiple HCCs.

Liver Resection Versus Liver Transplant
Liver transplant is an established treatment option for patients who have early-stage HCC and poorly compensated cirrhosis and/or portal hypertension. However, the preferred treatment of patients who have early-stage HCC and wellcompensated cirrhosis is not established. Several retrospective studies have evaluated outcomes after liver resection for HCC in this setting, comparing them with those of transplant. However, most are limited by small sample sizes and low statistical power. No prospective studies have been performed on this topic given the inability to randomize patients to liver resection versus transplant. The authors found 2 studies including more than 200 patients. They both suggest that transplant is associated with better survival than liver resection in patients within Milan criteria and Child-Pugh A or B. Nonetheless, it should be noted that graft availability and waiting times for transplant differ between countries, which greatly influences the selection of liver resection versus transplant for patients with early-stage HCC.

CONCLUSION

The current evidence suggests that, for patients with small HCC lesions (<3 cm), OS is likely to be similar for patients undergoing liver resection versus ablation. For selected patients with multiple HCCs, liver resection may be associated with better OS than TACE. For the past 10 years, sorafenib has been the only effective medical therapy available for unresectable HCC. Recently, several promising new therapies, including multikinase inhibitors and immunotherapies, have been reported. Perioperative use of these new therapies may further improve outcomes in patients undergoing liver resection for HCC and potentially change the current treatment guidelines.

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