Invited Lecture (JSH)
November 3 (Thu.), 9:00–9:40, Room 4 (Portopia Hotel South Wing Ohwada A)
Invited Lecture-11

How ultrasound guidance impacts HCC guidelines

G. Torzilli
Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University and Humanitas Research Hospital
Liver surgery has become an established therapy for patient with hepatocellular carcinoma (HCC) on cirrhosis. However, controversies remain between surgeons and oncologists in regard to the tumor burden suitable to be surgically removed with adequate survival. Indeed, in the current guidelines (1), surgery is confined to those patients in the very early or early stages of disease (Barcelona Clinic LC 0-A). However, several studies have shown a more than potential role of surgery for patients with large, multinodular and macrovascular invasive HCC (BCLC B and C). Furthermore, surgery disappeared as a suitable treatment for patients with intermediate and advanced HCC on the basis of randomized trials in which unresectability was the main inclusion criteria in that admitting surgery as the best treatment of choice whenever suitable (2-4)
Certainly surgery has to be carried out in tertiary referral centers and in a parenchyma sparing and anatomical fashion. Parenchyma sparing (5), and anatomical fashion (6) means imaging guidance and imaging guidance means essentially ultrasound guided surgery (7). Within this perspective surgery of HCC has proven to be a safe approach (8) even utilizing simple selection criteria (9), and even once offered to patients with advanced disease (10,11).
A recent multicentric study showed that the 5-year overall survival of patients within the stages B and C were 57% and 38% respectively (12). That study was criticized as biased by the misinterpretation of the class B, which should have been considered inclusive of just those patients with multinodular HCC, while those with single and larger than 5 cm HCC should have not. It is evident by the literature that there is a lack of clarity in the classification (1,13,14), if even in the latest releases the B class includes also those patients with single, larger than 5 cm HCC in one (1), and does not in the other (13). On the other hand it should be clarified the rationale based on which a large HCC, if not intermediate, could be defined as early: recently on this issue there has been a release supporting the inclusion of the large HCC within the B class (15). In any case, wherever B class should be inclusive or not of large HCC, the aforementioned multicentric study (12) showed that 50% of patients carrier of intermediate or advanced HCC are treated routinely with surgery in tertiary referral centers worldwide representative. This is undoubtedly sustaining, that surgery is not an anecdotal solution for these patients, and the remarkable survival is not justifying exclusion a priori of surgery from the available therapies. Following this snapshot, a nomogram based on that multicentric series has been proposed for aiding physician in realizing the prognostic benefit provided by the surgical treatment according to HCC stage (16). Thus, surgery should at least be considered in a multidisciplinary setting as a potentially curative therapy also for patients in stage B and C of the BCLC and a therapeutic flow-chart for these patients should recognize this role.

1. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56(4): 908-43
2. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002; 35:1164-1171
3. Llovet JM, Real MI, Montana X, et al. Arterial embolization or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734-1739
4. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390
5. Torzilli G, Montorsi M, Donadon M, et al. "Radical but conservative" is the main goal for ultrasonography-guided liver resection: prospective validation of this approach. J Am Coll Surg 2005;201:517-528
6. Hasegawa K, Kokudo N, Imamura H, et al. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg 2005;242:252-259
7. Torzilli G, Makuuchi M, Inoue K, et al. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg 1999;134:984-992
8. Donadon M, Costa G, Cimino M, et al. Safe hepatectomy selection criteria for hepatocellular carcinoma patients: a validation of 336 consecutive hepatectomies. The BILCHE score. World J Surg. 2015;39:237-243
9. Torzilli G, Donadon M, Marconi M, et al. Hepatectomy for stage B and stage C hepatocellular carcinoma in the Barcelona Clinic Liver Cancer classification: results of a prospective analysis. Arch Surg. 2008;143:1082-1090
10. Ishizawa T, Hasegawa K, Aoki T, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008;134:1908-1916
11. Torzilli G, Belghiti J, Kokudo N et al. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West study group. Ann Surg 2013;257(5):929-937.
12. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet, 2012; 379(9822): 1245-55
13. Torzilli G, Belghiti J, Kokudo N, et al. Reply to Letter: "Dissecting EASL/AASLD Recommendations With a More Careful Knife: A Comment on 'Surgical Misinterpretation' of the BCLC Staging System": Real Misinterpretation or Lack of Clarity Within the BCLC? Ann Surg. 2015; 262(1): e18-9
14. Jung YK, Jung CH, Seo YS, et al. BCLC stage B is a better designation for single large hepatocellular carcinoma than BCLC stage A. J Gastroenterol Hepatol. 2015 Sep 1. doi: 10.1111/jgh.13152. [Epub ahead of print]
15. Torzilli G, Donadon M, Belghiti J, et al. Predicting individual survival after hepatectomy for Hepatocellular Carcinoma: a novel nomogram from the "HCC East & West Study Group". J Gastrointest Surg, 2016; 20(6): 1154-62
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