For DebateLiver resection for HCC with cirrhosis: Surgical perspectives out of EASL/AASLD guidelines
Introduction
Hepatocellular carcinoma (HCC) with cirrhosis is the fifth tumor in the world and it is the most common primary neoplasm of the liver.1, 2 Three treatment options can be considered as radical therapies for this tumor: liver transplantation, liver resection, and radiofrequency thermal ablation. The indications for different treatments are widely debated and overlapping: the best candidates for each option are the same.
EASL (European Association for Study of Liver) in 20011 and AASLD (American Associations for Study of Liver Diseases) in 20052 published guidelines for HCC treatment trying to define the role of each therapeutic option. They reported well-defined indications for hepatectomy for HCC: patients with single HCC and completely preserved liver function without portal hypertension. Nodule size was not considered a limit to hepatic operation but the authors emphasized that it is uncommon to resect tumors larger than 5 cm because of the high risk of vascular invasion. Considering the strict indications for liver transplantation (Milan criteria) and for interstitial treatments (≤3 cm), according to EASL/AASLD guidelines, a large portion of patients affected by HCC should be scheduled for non-curative treatments. In order to offer a chance of cure to a larger number of patients, the most experienced surgical centers continue to perform liver resections out of EASL/AASLD indications, suggesting that good long-term results are achievable, better than those reported after non-curative treatments.
The aim of our analysis is to review data available in the literature in order to discuss results of liver resection out of EASL/AASLD indications, i.e. in patients affected by
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large HCC
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multinodular HCC
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HCC with portal vein thrombosis
Moreover, we will discuss surgical results in the presence of portal hypertension, a contraindication to operation according to the EASL/AASLD point of view.
Section snippets
Large HCC
Even if screening programs for patients affected by hepatic cirrhosis allow an increasing number of diagnoses of small HCC, large tumors are still frequent.3 In Japan 10–20% of newly diagnosed HCCs are larger than 10 cm.4 These patients are not suitable for interstitial treatments and they are excluded from transplantation programs.1, 2 EASL/AASLD guidelines suggest that resection for HCCs larger than 5 cm should be exceptional because of the high rate of vascular invasion and the dismal
Multinodular HCC
HCC is frequently a multicenter disease. EASL/AASLD guidelines considered the presence of multiple nodules as a contraindication to liver resection and liver transplantation is accepted only within Milan criteria (three nodules ≤3 cm)1, 2; similar indications have been considered for interstitial treatments. All patients with multiple HCCs beyond these strict indications should be scheduled for non-curative therapies. These data are based on the high risk of postoperative recurrence.15
The
Portal vein thrombosis
During the natural history of HCC with cirrhosis, tumor invasion of portal pedicles and the main portal trunk is common. The Liver Cancer Study Group of Japan reported a thrombosis incidence of 62% in the portal vein and of 26% in the hepatic vein at autopsy.27 Portal vein thrombosis (PVT) incidence in surgical series is about 5–15%.28 According to EASL/AASLD guidelines, these patients should be considered for non-curative therapies because of the dismal prognosis and the high risk of
Portal hypertension
EASL/AASLD guidelines considered portal hypertension as a contraindication to liver resection and referred these patients for other treatments.1, 2 This evaluation has been based on Barcelona group studies. In 1996, Bruix analysed 29 Child-Pugh A class cirrhotic patients undergoing liver resection for HCC with preoperative measurement of hepatic venous pressure gradient (HVPG).35 At multivariate analysis HVPG ≥ 10 mmHg was the most powerful predictor of postoperative liver decompensation. These
Surgical series and EASL/AASLD guidelines
We reviewed the presence of debated characteristics in large published series20, 40, 41, 44, 45, 46 (Table 1). All the most experienced surgical teams usually treated patients with HCC beyond EASL/AASLD criteria, large tumors (30–75%), multinodular disease (25–40%) and HCC with major vascular invasion (3–15%).
In our series published in 2005,23 216 patients underwent hepatectomy for HCC with cirrhosis between 1985 and 2001; we focused our attention on 169 Child-Pugh A patients. Forty-one
Conclusions
EASL/AASLD guidelines clearly define indications for hepatic resection for HCC: patients with single HCC and completely preserved liver function without portal hypertension. These guidelines exclude from operation many patients that could benefit from radical resection and that are daily scheduled for hepatectomy in surgical centers. Patients with large tumors or with portal vein thrombosis cannot be transplanted or treated by interstitial treatments. In selected cases hepatic resection may
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