Response to Letter: Hepatocellular Carcinoma

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To the Editor:
We are thankful to Kokudo et al for their interest in our article1 and insightful comments. These authors have highlighted important differences in the management of hepatocellular carcinoma (HCC) between the East and the West with regards to the use of indocyanine green retention at 15 minutes (ICG-R15) and resection of HCC with macrovascular invasion (MVI).
Liver function can be determined by various methods such as laboratory parameters, risk-scoring systems such as model for end stage liver disease (MELD), assessing the severity of underlying portal hypertension, and also dynamic tests such as ICG-R15. Although ICG-R15 has been widely utilized in the East, for various reasons, including limited validation, it has not been widely used in the West.2 It is probable that with the publication of data by Kokudo et al,3 more Western centers may incorporate this dynamic method into routine clinical practice. It is likely that multiple tools may be needed to assess the extent of underlying liver disease and promising new tools such as albumin-indocyanine green evaluation grade (ALICE grade) will continue to improve our ability to risk-stratify patients before hepatic resection. The authors also note that portal hypertension is no longer a contraindication for hepatic resection. Although some studies have documented hepatic resection in the presence of portal hypertension, it is still a major risk factor contributing to mortality and morbidity.4 The study by Berzigotti et al5 noted that the presence of clinically significant portal hypertension (CSPH) contributed to a statistically significant and higher 3 and 5-year mortality versus patients without CSPH [odds ratio (OR) 2.09]. CSPH also increased the risk of postoperative clinical decompensation (OR 3.04).
Similarly, liver resection (LR) in patients with HCC with MVI of the main or first-order branches of the portal vein (PV) remains a point of debate worldwide.4 To overcome the limitation of small sample size of the studies published on the subject, Kokudo et al have conducted a well-designed study using the registry data of 77, 268 patients with HCC (2000–2007). A total of 6474 patients with portal vein thrombosis (PVT) were analyzed including patients with HCC and main PV, and first, second, and third-order PV branch involvement. In a propensity score analysis, median overall survival (OS) in the LR group was 0.88 years longer than the non-LR group (2.45 vs 1.57 years; P < 0.001). However, performance status or comorbidities of the patients were not taken into account in the propensity match as these factors can significantly affect survival. Additionally, over 30% of the patients in the non-LR group were treated with chemotherapy or best supportive care which may have biased their results in favor of LR. Finally, there was no survival advantage amongst patients with main PV or first-order branch involvement treated with LR (median OS 9 months), and these patients had a 90-day postoperative mortality of 8.2% which is quite significant.
In summary, variations in clinical practice exist across the world, which could be due to various reasons such as differences in tumor biology and etiology, environmental influences, mode/stage of presentation, or could be related to training and practice patterns. For example, although studies in the West have shown a lack of benefit in some cancers such as pancreas and stomach, extended lymphadenectomy continues to be performed in the East.6–8 Contrast-enhanced ultrasound is not routinely used in United States, although its benefits have been documented in the East.9 Finally, practice patterns across the world do not always uniformly follow the strict algorithm-based treatment recommendations due to variations in interpretation of the algorithms.

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