ALPPS Procedure for Hepatocellular Carcinoma in Patients With Chronic Liver Disease: Revealing a Terra Incognita

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To the Editor:
We read with great interest the recent publication of Chan et al1 presenting their breakthrough results on anterior approach ALPPS for hepatocellular carcinoma (HCC) in patients with chronic liver disease that the group from Hong Kong has pioneered.2,3
The rising interest in ALPPS has, and will further, evaluate the efficacy of technical innovations such as the use of the anterior approach to address the initial concern about high complication rates and long-term survival.4 In order a novelty to gain fidelity, the dominance of its advantages against its obstacles and the complete understanding of the pathophysiology of each disease, that a modality should treat, are crucial.
As far as the technical analysis of this approach is concerned, it seems that it offers significant advantages in treating HCC in cirrhotic patients. By allowing a complete parenchymal dissection down to the inferior vena cava without prior mobilization of the right liver, the amount of adhesions was found to be much less. This is of great importance, since the presence of several hypervascularized adhesions is very common in cirrhotic patients and makes any reintervention very challenging. The latter can have an impact on perioperative morbidity in terms of bowel injury and bleeding. Furthermore, anterior approach avoids iatrogenic tumor rupture during right liver mobilization, which may put in jeopardy the safety and efficacy of the Stage II operation.2 Besides, judicious use of radiofrequency energy devices facilitates exposure and meticulous control before division of intraparenchymal bile ducts. Thus, the chance of bile leakage and further negate the use of plastic bag is minimized.2
Beyond these advantages, the indications of the application of ALPPS in cirrhosis are not well established. Despite the fact that the approach seems feasible for HCC in Child–Pugh A patients, there are not clear data about its role in patients with Child–Pugh B or C grade liver function. Moreover, it was recently shown that beyond Child–Pugh grading, the morphologic severity of cirrhosis is an independent predictor of post-hepatectomy liver failure. Thus, the extent of resection should be inversely correlated with the severity of the cirrhosis.5
Moreover, no data about the oncological safety and the follow-up are demonstrated. That would be of importance, since the ultimate “judge” of every new technique, especially when applied in oncological patients, is its efficacy and the disease-free survival. Additionally, there is high heterogeneity of the selection of the patients in terms of number of tumors and its size.
Another issue to highlight is that, despite the fact that all patients were deemed appropriate for Stage II operation, there was a great heterogeneity of the days needed to proceed to Stage II among patients. The reason for this difference is not clear and there are no data about the possible differences between the patients who had chronic HBV infection compared with cirrhotic ones. Furthermore, the authors evaluated the efficacy of ALPPS in a patient group with an age range of 30 years. Age differences could have an impact on data interpretation since it is also thought as a factor that could predispose to different liver regenerative and functional potential. It was recently shown in an experimental model that older age was correlated with impaired liver regeneration after liver resection, which was expressed by decreased cell cycle activity and increased autophagy and programmed cell death.6
The authors claimed that the differences of post-hepatectomy liver regenerative potential, between patients with metastatic disease in an otherwise normal liver and patients with HCC in chronic liver disease, are reasonable.

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