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      The Negative Effect of Preoperative Transcatheter Arterial Chemoembolization on Long-Term Outcomes for Resectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

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          Abstract

          Background

          Preoperative transcatheter arterial chemoembolization (TACE) is administered to improve long-term outcome after surgical resection of hepatocellular carcinoma (HCC). However, the survival benefit of preoperative TACE is controversial. We conducted a retrospective case-control study to evaluate the effect of preoperative TACE on prognosis.

          Methods

          A total of 121 patients who underwent curative resection of HCC were divided into two groups according to whether they received preoperative TACE. We determined the control group ( n = 34) and TACE group ( n = 34) through propensity score matching. The primary endpoint of this study was overall survival, and the secondary endpoints were recurrence-free survival.

          Results

          The overall survival rate and the recurrence free survival rate were significantly lower in the TACE group than in the control group ( P = 0.014 and P = 0.043, respectively). Furthermore, recurrence free survival within less than 2 years after resection was significantly worse in the TACE group than in the control group ( P = 0.035).

          Conclusion

          Preoperative TACE seemed to worsen the long-term outcomes of the patients who underwent surgical resection for the treatment of resectable HCC. Therefore, preoperative TACE should not be considered as a standard therapy in patients with resectable HCC.

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          Most cited references25

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          Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy.

          Hiroshi Imamura, Yutaka Matsuyama, Eiji Tanaka … (2003)
          We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC). The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years. Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level >or=32 ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification. Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.
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            A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma.

            Sasan Roayaie, Iris N Blume, Swan Thung … (2009)
            Hepatocellular carcinoma (HCC) recurs in approximately 70% of cases after resection. Vascular invasion by tumor cells can be classified as gross or microscopic (microvascular invasion [mVI]) and is a risk factor for recurrence. We examined a large cohort of patients with HCC who were treated by resection to identify features of mVI that correlated with recurrence and survival. We reviewed the records of all HCC resections performed at the Mount Sinai School of Medicine between January 1990 and March 2006 to identify those with mVI, established by histologic analysis. The numbers and sizes of vessels invaded, invasion of a vessel with a muscular wall, distance from the tumor, and satellite nodules were recorded. Of the 384 patients who underwent resection for HCC, 131 (34.1%) met the entry criteria. The median follow-up period was 28.9 months. There were 68 recurrences and 54 deaths. In multivariate analysis, invasion of a vessel with a muscular wall predicted recurrence (hazard ratio, 1.8; P = .02), and invasion of a vessel with a muscular wall (hazard ratio, 2.2; P = .018) and invasion of a vessel that was more than 1 cm from the tumor (hazard ratio, 2.1; P = .015) predicted survival. A risk score that assigned points for the presence of each variable correlated with recurrence (P = .028) and survival (P < .0001). A novel classification system that includes invasion of a vessel with a muscular wall and invasion of a vessel that is more than 1 cm from the tumor can accurately predict risk of recurrence and survival of patients with mVI after resection of HCC.
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              Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.

              Ronnie Tung-Ping Poon, Sheung-Tat Fan, John Wong (2000)
              To evaluate the current knowledge on the risk factors for recurrence, efficacy of adjuvant therapy in preventing recurrence, and the optimal management of recurrence after resection of hepatocellular carcinoma (HCC). The long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. Prevention and effective management of recurrence are the most important strategies to improve the long-term survival results. A review of relevant English articles was undertaken based on a Medline search from January 1980 to July 1999. Pathologic factors indicative of tumor invasiveness such as venous invasion, presence of satellite nodules, large tumor size, and advanced pTNM stage, are the best-established risk factors for recurrence. Active hepatitis activity in the nontumorous liver and perioperative transfusion also appear to enhance recurrence. Recent molecular research has identified tumor biologic factors such as the proliferative and angiogenic activities of the tumor as new risk factors for recurrence. There is a lack of convincing evidence for the efficacy of neoadjuvant or adjuvant therapy in preventing recurrence. Retrospective studies suggested that postoperative hepatic arterial chemotherapy might improve disease-free survival, but results were conflicting. For the management of postoperative recurrence, studies have consistently indicated that surgical resection should be the treatment of choice for localized recurrence, be it in the liver remnant or extrahepatic organs. Transarterial chemoembolization and percutaneous ethanol injection are widely used to prolong survival in patients with unresectable intrahepatic recurrence, and combined therapy with these two modalities may offer additional benefit. Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to prevention. Minimal surgical manipulation of tumors to prevent tumor cell dissemination, avoidance of perioperative blood transfusion, and suppression of chronic hepatitis activity in the liver remnant are strategies that may be useful in preventing recurrence. The efficacy of postoperative adjuvant regional chemotherapy deserves further evaluation. New concepts on the influence of tumor biologic factors such as angiogenic activity on recurrence of HCC suggest a potential role of novel approaches such as antiangiogenesis for adjuvant therapy in the future. Currently, the most realistic approach in prolonging survival after resection of HCC is early detection and aggressive management of recurrence. Randomized trials are needed to define the roles of various treatment modalities for recurrence and the benefit of multimodality therapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Yonago Acta Med
                Journal ID (iso-abbrev): Yonago Acta Med
                Journal ID (publisher-id): YAm
                Title: Yonago Acta Medica
                Publisher: Tottori University Faculty of Medicine
                ISSN (Print): 0513-5710
                ISSN (Electronic): 1346-8049
                Publication date (Electronic): 26 December 2016
                Publication date Collection: December 2016
                Volume: 59
                Issue: 4
                Pages: 270-278
                Affiliations
                [1]*Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
                [2]†Division of Radiology, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan
                Author notes
                Corresponding author: Masataka Amisaki, MD
                amisakim@ 123456med.tottori-u.ac.jp
                Article
                Publisher ID: yam-59-270
                PMC ID: 5214693
                PubMed ID: 28070164
                SO-VID: c9dea1a6-adec-43e0-80e0-333f85cbe881
                Copyright © 2016 Yonago Acta medica
                History
                Date received : 15 September 2016
                Date accepted : 24 October 2016
                Categories
                Subject: Original Article
                Custom metadata
                Abbreviations AFP, alpha-fetoprotein; ALT, alanine transaminase; AST, aspartate transaminase; CT, computed tomography; HCC, hepatocellular carcinoma; ICG-R15, rate of indocyanine green disappearance 15 min after injection; IRB, institutional review board; MRI, magnetic resonance imaging; TACE, transcatheter arterial chemoembolization

                Keywords: surgical resection,survival,hepatectomy,neoadjuvant
                Data availability:
                Keywords: surgical resection, survival, hepatectomy, neoadjuvant

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