Abstract
Backgrounds
In the era of multidisciplinary treatment strategy, resectability for hepatocellular carcinoma (HCC) should be defined. This study aimed to propose and validate a resectability classification of HCC.
Methods
We proposed following the three groups; resectable-(R), borderline resectable-(BR), and unresectable (UR)-HCCs. Resectable two groups were sub-divided according to the value of indocyanine green clearance of remnant liver (ICG-Krem) and presence of macrovascular invasion (MVI); BR-HCC was defined as resectable HCCs with MVI and/or ICG-Krem≥0.03–<0.05, and R-HCC was the remaining. Consecutive patients with HCC who underwent liver resection (LR) and non-surgical treatment(s) (i.e., UR-HCC) between 2011 and 2017 were retrospectively analyzed to validate the proposed classification.
Results
A total of 361 patients were enrolled in the study. Of these, R-, BR- and UR-HCC were found in 251, 46, and 64 patients, respectively. In patients with resected HCC, ICG-Krem≥0.05 was associated with decreased risk of clinically relevant posthepatectomy liver failure (p=0.013) and the presence of MVI was associated with worse overall survival (OS) (p<0.001). The 3–5-years OS rates according to the proposed classification were 80.3, and 68.3% versus 51.4, and 35.6%, in the R and BR groups, respectively (both p<0.001). Multivariate analysis showed BR-HCC was independently associated with poorer OS (p<0.001) after adjusting for known tumor prognostic factors. Meanwhile, BR-HCC was associated with benefit in terms of OS compared with UR-HCC (p<0.001).
Conclusion
Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC and may help to determine treatment strategy.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, showing a worldwide increasing incidence [1, 2]. Among the available treatment options, liver resection (LR) is one of the most common treatments which yields long-term survival for selected patients with HCC [3, 4]. Especially, aggressive surgical procedures such as vascular resection/reconstruction may allow for achieving R0 resection in advanced cases; however, long-term outcomes for these patients still remain unsatisfactory [5]. Therefore, further improvement of the treatment strategy would be required.
To refine the treatment strategy, we would like to propose a concept of “resectability” for HCC. The concept of resectability was initiated in patients with pancreatic cancer and might allow for developing a new treatment strategy [6]. Resectability classification consists of three categories; resectable (R), borderline resectable (BR), and unresectable (UR) diseases [7]. Of these, the definition of BR should be debatable and BR seems to comprise surgical/anatomical complexity as well as oncological disadvantages [6, 7]. In other words, BR tumors represent worse survival than R tumors and surgery may provide limited benefit for patients with BR tumors in current practice; meanwhile, BR tumors require more complicated surgical technique to achieve R0 resection than R tumors (i.e., risk of residual tumor).
In the era of multidisciplinary treatment, the concept of resectability may have a potential to develop a new treatment strategy in patients with HCC; however, its application for HCC remains ill-defined. The main reason was that the balance between liver function and tumor progression should be taken into consideration for HCC. To date, some criteria combining liver and tumor factors (e.g., Barcelona Clinic Liver Cancer staging [1], or Cancer of the Liver Italian Program score [8]) have been adopted in the clinical practice; however, these criteria were not specified in patients undergoing LR. In the context of focusing on LR-specific population, we propose BR-HCC as a high-risk group of posthepatectomy liver failure (PHLF) and/or advanced disease (Fig. 1); indocyanine green clearance of remnant liver (ICG-Krem) and macrovascular invasion (MVI) were selected as determinants of BR-HCC based on our previous data, published series and practical guidelines [1, 2, 9,10,11,12,13,14]. The aim of the present study was to propose a classification of resectability for HCC combining these two factors and assess whether this classification could stratify the survival outcomes in patients with HCC.
Methods
Study design
The protocol of this retrospective observational study was approved by Kyoto University Graduate School and Faculty of Medicine, Ethics Committee (approval code: R3013). Written informed consent was obtained from all study participants.
Proposal of resectability classification for HCC
Our conceptual classification of resectability for HCC is shown in Fig. 2. UR-HCC was defined as the disease with distant metastasis or inability for macroscopic curative resection. Among the resectable disease, BR-HCC was defined as a high-risk group of clinically relevant PHLF (CR-PHLF) assessed by ICG-Krem and/or HCC with MVI (HCC-MVI); R-HCC was the remaining.
Proposed resectability classification of HCC. *Macrovascular invasion was defined as involvement of Vp2-Vp4 and/or Vv2-Vv3 according to the Japanese staging system [17]. Abbreviations: HCC hepatocellular carcinoma
Risk assessment of PHLF should be prioritized, and a combination of the future liver remnant volume (FLRV) and the parameter of liver functional preserve may be its determinant [15]. ICG-Krem, which most hepatobiliary centers routinely measure in Japan, simultaneously balances these two aspects and therefore we selected it as an indicator of a high-risk group of CR-PHLF. ICG-Krem was calculated using the following formula with reference to a previous study [13]: ICG-Krem=preoperative ICG-K (ICG clearance)×FLRV / total liver volume (TLV). In our center, ICG-Krem<0.03 was defined as contraindication for LR (i.e., UR-HCC) [10]; ICG-Krem<0.05–≥0.03 was set as high-risk of CR-PHLF according to the previous studies (i.e., BR-HCC) [10, 13, 14].
We also selected MVI as an indicator of tumor progression based on the fact that MVI represents surgical/anatomical complexity as well as oncological disadvantages [1, 2, 9, 16]. MVI was defined as involvement of Vp2-Vp4 and/or Vv2-Vv3 according to the Japanese staging system [9, 17], where Vp2, Vp3, and Vp4 represent portal vein tumor thrombosis (PVTT) in the second-order branch, first-order branch, and main trunk/contralateral branch of the portal vein, respectively; where Vv2 and Vv3 represent hepatic vein tumor thrombosis (HVTT) in the first branch of the hepatic vein and inferior vena cava (IVC), respectively. From the technical aspects [18, 19] and the Hong Kong Liver Cancer classification [20], MVI was further classified into intra- (i.e., Vp2, Vp3, and Vv2) and extra-hepatic (i.e., Vp4 and Vv3) ones.
Patients
We reviewed a prospectively maintained institutional database of consecutive patients who underwent LR (LR study population) and non-surgical treatment(s) for HCC at the Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, between January 2011 and December 2017.
In the LR study population, the inclusion criteria were (1) patients with histologically diagnosed HCC. Exclusion criteria were (1) patients with apparent distant metastasis detected on computed tomography (CT), magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography or intraoperatively; (2) patients unavailable for prospective CT volumetry and/or ICG measurement; (3) patients who underwent repeated LR during the study period; (4) patients who underwent LR and concomitant ablative therapy because it was impossible for calculating actual ICG-Krem. Patients were divided into the two groups; R- and BR-HCC groups. Our database also included patients with HCC who were referred to our department to explore resectability, but eventually not indicated for LR; these patients were used as a control subject (i.e., UR-HCC group).
Clinicopathological data including sex, age, hepatitis virus markers, treatment-related variables, and survival data were retrieved from the database. Tumor characteristics including MVI were determined by the final clinicopathological findings. Routinely, ICG was administered intravenously at a dose of 0.5 mg/kg for assessing liver function within 2 weeks before LR. For the volume assessment, volumetric computed tomography was performed using a Virtual Place Lexus workstation (AZE, Tokyo, Japan) and SYNAPSE VINCENT (FUJITSU Tokyo) [10, 21]. Postoperative complications were defined according to the Clavien-Dindo classification [22]; complication was defined Clavien-Dindo≥grade II. CR-PHLF was defined as PHLF≥grade B according to the classification of the International Study Group of Liver Surgery (ISGLS) [23]. The follow-up protocol was previously reported [24].
Surgical strategy of LR for HCC
The indications for LR included a CP grade of A or B, and ICG-Krem<0.03 is defined as a contraindication. Surgical procedures of LR were reported elsewhere [24, 25]. During the study period, postoperative hepatic arterial infusion therapy (HAIC) was administered for Vp3-Vp4 cases if appropriate [11]. In cases of advanced Vv3, preoperative HAIC rather than immediate resection was firstly considered [12]. Sorafenib, radiation therapy, and transcatheter arterial chemoembolization were added as supportive treatments for HAIC. Advanced Vv3 was defined as the following: (1) suspected extrahepatic metastasis; (2) the expected need for extracorporeal circulation, (e.g., right atrial tumor thrombus); (3) marginal liver function (i.e., ICG-Krem<0.05); and 4) multiple bilobar tumors. During the study period, postoperative sorafenib was administrated for patients with HVTT if appropriate [12].
Statistical analysis
Categorical variables were analyzed with Chi-square test and Fisher’s exact test as appropriate. Continuous variables were analyzed using the Mann–Whitney U test. Overall survival (OS) was calculated from the date of operation (R- and BR-HCC) or the date of admission (UR-HCC) until death due to any cause, or the date of the last follow-up. Recurrence-free survival (RFS) was calculated from the date of the operation (R- and BR-HCC only) until the date of recurrence, or any cause of death. Survival curves were estimated using the Kaplan–Meier method, and a comparison was performed with the long-rank test. A multivariate analysis was performed using the Cox regression model using selected variables for variables with p<0.100 in univariate analysis. When collinearity was encountered, a choice was made based on the p value and clinical reasoning. All p values were two-sided and values less than 0.050 were considered statistically significant. Statistical analyses were performed using JMP Pro14.1 software (SAS Institute Inc., Cary, NC).
Results
Figure 3 shows a flow diagram of the present study. Between 2011 and 2017, 354 hepatectomies for HCC were performed. According to the study definition, a total of 297 patients were included in the LR study; of these, 251 and 46 patients were found in the R- and BR-HCC groups, respectively. Patient demographics in the LR study population are shown in Table 1. Meanwhile, 64 patients were identified as UR-HCC. Patient demographics in the UR-HCC group are shown in Supplementary Table 1.
Validity to use ICG-Krem and MVI for defining BR-HCC
ICG-Krem < 0.05 is a significant risk factor of CR-PHLF
Median ICG-Krem was 0.099 (range, 0.036–0.345), and ICG-Krem<0.05 was found in 10 patients (3.3%). Of these, four patients (40%) preoperatively underwent portal vein embolization (PVE). No patients showed ICG-Krem<0.030 according to our strategy as aforementioned. Meanwhile, CR-PHLF was occurred in 31 patients (10.4%). ICG-Krem<0.05 was significantly associated with CR-PHLF (p=0.013, Fig. 4a).
Impact of MVI on survival outcomes in patients with HCC after LR
Next, we assess the survival outcomes in patients with MVI after LR. A total of 38 patients with HCC (12.8%) showed MVI; of these, 23 and 15 patients showed intrahepatic MVI (i.e., Vp2, Vp3, or Vv2) and extrahepatic MVI (i.e., Vp4 or Vv3), respectively. Meanwhile, 27 patients with HCC-MVI underwent some adjuvant therapie(s) (the main treatment; HAIC, n=22; sorafenib, n=5). Survival outcomes according to the grade of MVI are shown in Fig. 4b. Patients with MVI showed worse OS than those without (p<0.001); meanwhile, there was no significant difference with regards to OS between intrahepatic and extrahepatic MVIs (p=0.903, Fig. 4b).
Survival outcomes according to the proposed classification
Clinicopathological characteristics between the R- and BR-HCC groups are also shown in Table 1. Compared with the R-HCC group, BR-HCC group showed younger age, worse liver function, worse perioperative outcomes and aggressive tumor characteristics.
The median OS time and the 1, 3, and 5-year OS rates of patients in the R-HCC group were significantly better compared with the BR-HCC group (not reached and 94.8, 80.3, and 68.3% vs. 36.2 months and 75.4, 51.4, and 35.6% for R- vs. BR-HCC groups, respectively, p<0.001; Fig. 5). In the UR-HCC group, the median OS time, and 1, 3, and 5-year OS rates were 16.2 months and 65.1%, 16.3%, and 9.8%, respectively. Better OS were found in both the R- and BR-HCC groups compared with the UR-HCC group (both p<0.001). The median RFS time and the 1, 3, and 5-year RF rates of patients in the R-HCC group were significantly better compared with the BR-HCC group (35.0 months, and 75.8%, 47.7% and 40.8% vs. 8.9 months, and 33.9, 23.5 and 20.1% for R- vs. BR-HCC groups, respectively, p<0.001, Supplemental Fig. 1).
To assess the prognostic independency of the proposed BR-HCC, multivariate analysis for OS was performed in the LR study population. Seven selected factors which might be preoperatively available were entered into the multivariate model. After adjusting for these factors, BR-HCC was independently associated with poorer OS (hazard ratio: 2.597, 95% confidence interval; 1.558–4.329, p<0.001, Table 2).
Discussion
In the era of multidisciplinary approach or multiple choice of treatments for malignancies, refinement of surgical strategy for HCC would be required. In this context, we proposed a resectability classification of HCC which consisted of three categories; R-, BR-, and UR-HCCs. We defined BR-HCC, the most debatable subgroup, as a high-risk group of PHLF assessed by ICG-Krem and/or HCC-MVI. In this setting, a proposed resectability classification significantly stratified OS among the R-, BR-and UR-HCCs.
The concept of resectability was initiated in pancreatic cancer and has already been accepted worldwide [6, 7], yet, its application for HCC remains ill-defined. From a surgical perspective for HCC, liver function and tumor progression should be balanced. Of note, liver function should be prioritized the most to avoid postoperative mortality, and therefore, many guidelines prioritized assessment of liver function [1, 2]. According to our recent systematic review, preoperative FLRV and the status of portal hyper-pressure seem to determine the PHLF [15]. This study advocated the use of ICG-Krem. The reason was that measurement of ICG is a standard practice for determining surgical indication in liver surgery especially in Japan [27] and many investigators have reported that ICG-Krem<0.05 was a significant risk factor of PHLF [10, 13, 14].
Meanwhile, we focused on MVI as a tumor factor for resectability classification based on its anatomical/surgical complexity as well as poor prognosis [28, 29]. From the oncological aspect, the European Association for the Study of Liver disease guideline does not recommend LR for HCC-MVI; meanwhile, a Japanese national-wide study reported that LR for selected HCC-MVI (e.g., up to Vp3 in PVTT cases) might be associated with benefit compared with non-surgical therapy [28, 29]. This controversy prompted us to include MVI into the resectability classification of HCC. Although we investigated the prognostic impact of intrahepatic and extrahepatic MVIs based on the surgical difficulty or tumor aggressiveness [12, 18, 19], their prognostic value was comparable. Therefore, HCC-MVI would not be sub-divided. We have taken several efforts to improve the long-term outcomes of HCC-MVI; postoperative HAIC was administrated for Vp3-Vp4 cases to prevent early intrahepatic recurrence [11], and preoperative HAIC was administrated for advanced Vv3 to evaluate the biological aggressiveness because those who progress under chemotherapy may not benefit from LR [12]. These strategies were associated with benefit, suggesting LR and some additional therapy may have a potential to improve survival outcomes of these patients.
The definition of BR-HCC represents clinical relevance for developing a new treatment strategy or contribution to future prospective studies in the era of multidisciplinary treatment strategy. In this study, BR-HCC was identified as an only independent prognostic factor in patients with HCC who underwent LR, and therefore, our classification may have a potential for these perspectives. For one example, we propose neoadjuvant therapy for expecting downsizing the tumor or biological change especially for BR-HCC in line with pancreatic cancer [6, 7]. Downsizing the tumor may change surgical procedures, which may result in increasing the FLRV/TLV and decreasing the risk of PHLF. As demonstrated by a recent randomized control trial (RCT) [30], effective preoperative therapy can prolong survival in patients with HCC-MVI. Besides, it should be noted that neoadjuvant therapy has another aspect to identifying its good responders. Considering these aspects, neoadjuvant strategy is worthwhile to be considered to improve the outcomes of BR-HCC and future RCT may allow for determining the best neoadjuvant approach. For the other examples, macroscopically no-margin LR which prioritizes the liver function [31], or preoperative PVE to increase the FLRV [32] may be selected. Besides, non-surgical approach (e.g., systemic chemotherapy) may be considered according to the overall patients’ condition.
A recent retrospective study demonstrated a possible role of chemotherapy that might allow patients with UR-HCC to become eligible for LR (i.e., “conversion” LR) [33]. At a present, LR might provide benefit for selected patients in our practice (Fig. 5). Although UR-HCC represents a dismal prognosis, conversion LR may shed a light for these patients and clinicians should not miss the chance.
Several limitations of this study should be pointed out. The main limitation of this study was that this resectability classification was derived from a single institution’s experience. To assess the validity of this classification, we used a different cohort from previous ones [10,11,12]. To assess the further validity of our proposal, external studies would be required. Secondly, the true contribution of LR for BR-HCC on long-term survival remains unknown. This was also biased by a single institutional analysis. Lastly, the disadvantage of ICG clearance (e.g., flow-dependency or unavailability in some countries) may limit generalization of our proposal for overall the world. According to our recent systematic review [15], combination of the FLRV and the parameter of liver functional preserve determines the occurrence of PHLF; however, the most general parameter of liver function is not clarified. At present, we consider ICG-Krem is the most reproducible parameter for assessing risk of PHLF based on our experience and recent studies [10, 13,14,15]. When unavailable for ICG, alternative parameter(s) (e.g., platelet count, albumin levels, liver stiffness by elastography, etc. [15]) should be used and further studies would be required for this context. Despite these limitations, we believe this classification contributes to the development of a new treatment strategy and is worthwhile to be validated by other centers.
Conclusions
Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC. We hope the future prospective studies will be conducted using our resectability classification of HCC.
Change history
23 November 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00268-022-06838-w
References
European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943. https://doi.org/10.1016/j.jhep.2011.12.001
Bruix J, Sherman M (2011) American association for the study of liver diseases. management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022. https://doi.org/10.1002/hep.24199
Chang YJ, Chung KP, Chang YJ et al (2016) Long-term survival of patients undergoing liver resection for very large hepatocellular carcinomas. Br J Surg 103:1513–1520. https://doi.org/10.1002/bjs.10196
Torzilli G, Donadon M, Marconi M et al (2008) Hepatectomy for stage B and stage C hepatocellular carcinoma in the barcelona clinic liver cancer classification: results of a prospective analysis. Arch Surg 143:1082–1090. https://doi.org/10.1001/archsurg.143.11.1082
Hyun MH, Lee YS, Kim JH et al (2018) Hepatic resection compared to chemoembolization in intermediate- to advanced-stage hepatocellular carcinoma: a meta-analysis of high-quality studies. Hepatology 68:977–993. https://doi.org/10.1002/hep.29883
Truty MJ, Kendrick ML, Nagorney DM et al (2021) Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Ann Surg 273:341–349. https://doi.org/10.1097/SLA.0000000000003284
Tempero MA, Malafa MP, Al-Hawary M et al (2017) Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15:1028–1061. https://doi.org/10.6004/jnccn.2017.0131
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the cancer of the liver italian program (CLIP) investigators (1998). Hepatology, 28: 751–755 https://doi.org/10.1002/hep.510280322
Costentin CE, Ferrone CR, Arellano RS et al (2017) Hepatocellular carcinoma with macrovascular invasion: defining the optimal treatment strategy. Liver Cancer 6:360–374. https://doi.org/10.1159/000481315
Iguchi K, Hatano E, Yamanaka K et al (2015) Validation of the conventional resection criteria in patients with hepatocellular carcinoma in terms of the incidence of posthepatectomy liver failure and long-term prognosis. Dig Surg 32:344–351. https://doi.org/10.1159/000431189
Kojima H, Hatano E, Taura K et al (2015) Hepatic resection for hepatocellular carcinoma with tumor thrombus in the major portal vein. Dig Surg 32:413–420. https://doi.org/10.1159/000437375
Kasai Y, Hatano E, Seo S et al (2017) Proposal of selection criteria for operative resection of hepatocellular carcinoma with inferior vena cava tumor thrombus incorporating hepatic arterial infusion chemotherapy. Surgery 162:742–751. https://doi.org/10.1016/j.surg.2017.05.011
Kobayashi Y, Kiya Y, Sugawara T et al (2019) Expanded Makuuchi’s criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection. HPB (Oxford) 21:990–997. https://doi.org/10.1016/j.hpb.2018.12.001
Nagino M, Kamiya J, Nishio H et al (2006) Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up. Ann Surg 243:364–372. https://doi.org/10.1097/01.sla.0000201482.11876.14
Yoshino K, Yoh T, Taura K, Seo S et al (2021) A systematic review of prediction models for post-hepatectomy liver failure in patients undergoing liver surgery. HPB (Oxford) 23:1311–1320. https://doi.org/10.1016/j.hpb.2021.05.002
Lee MK 4th, Gao F, Strasberg SM (2016) Completion of a liver surgery complexity score and classification based on an international survey of experts. J Am Coll Surg 223:332–342. https://doi.org/10.1016/j.jamcollsurg.2016.03.039
Kudo M, Izumi N, Kokudo N et al (2011) Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan society of hepatology (JSH) 2010 updated version. Dig Dis 29:339–364. https://doi.org/10.1159/000327577
Yamamoto Y (2013) Ante-situm hepatic resection for tumors involving the confluence of hepatic veins and IVC. J Hepatobiliary Pancreat Sci 20:313–323. https://doi.org/10.1007/s00534-012-0525-7
Fukumoto T, Kido M, Takebe A et al (2017) New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch. Surg Today 47:1094–1103. https://doi.org/10.1007/s00595-017-1507-9
Yau T, Tang VY, Yao TJ et al (2014) Development of Hong Kong liver cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 146:1691–1700. https://doi.org/10.1053/j.gastro.2014.02.032
Nishio T, Taura K, Koyama Y et al (2016) Prediction of posthepatectomy liver failure based on liver stiffness measurement in patients with hepatocellular carcinoma. Surgery 159:399–408. https://doi.org/10.1016/j.surg.2015.06.024
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213. https://doi.org/10.1097/01.sla.0000133083.54934.ae
Rahbari NN, Garden OJ, Padbury R et al (2011) Posthepatectomy liver failure: a definition and grading by the international study group of liver surgery (ISGLS). Surgery 149:713–724. https://doi.org/10.1016/j.surg.2010.10.001
Yoh T, Seo S, Taura K et al (2021) Surgery for recurrent hepatocellular carcinoma: achieving long-term survival. Ann Surg 273:792–799. https://doi.org/10.1097/SLA.0000000000003358
Yoh T, Seo S, Ogiso S et al (2022) Learning process of laparoscopic liver resection and postoperative outcomes: chronological analysis of single-center 15-years’ experience. Surg Endosc 36:3398–3406. https://doi.org/10.1007/s00464-021-08660-2
Strasberg SM (2005) Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg 12:351–355. https://doi.org/10.1007/s00534-005-0999-7
Sunagawa Y, Yamada S, Kato Y et al (2021) Perioperative assessment of indocyanine green elimination rate accurately predicts postoperative liver failure in patients undergoing hepatectomy. J Hepatobiliary Pancreat Sci 28:86–9430. https://doi.org/10.1002/jhbp.833
Kokudo T, Hasegawa K, Matsuyama Y et al (2017) Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: a Japanese nationwide survey. Hepatology 66(510):517. https://doi.org/10.1002/hep.29225
Kokudo T, Hasegawa K, Matsuyama Y et al (2016) Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 65(938):943. https://doi.org/10.1016/j.jhep.2016.05.044
Wei X, Jiang Y, Zhang X, Feng S, Zhou B, Ye X, Xing H, Xu Y, Shi J, Guo W, Zhou D, Zhang H, Sun H, Huang C, Lu C, Zheng Y, Meng Y, Huang B, Cong W, Lau WY, Cheng S (2019) Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol 37:2141–2151. https://doi.org/10.1200/JCO.18.02184
Oguro S, Yoshimoto J, Imamura H et al (2018) Clinical significance of macroscopic no-margin hepatectomy for hepatocellular carcinoma. HPB (Oxford) 20:872–880. https://doi.org/10.1016/j.hpb.2018.03.012
Shindoh J, Tzeng DCW, Vauthey JN (2012) Portal vein embolization for hepatocellular carcinoma. Liver Cancer 1:159–167. https://doi.org/10.1159/000343829
Zhu XD, Huang C, Shen YH, Ji Y et al (2021) Downstaging and resection of initially unresectable hepatocellular carcinoma with tyrosine kinase inhibitor and anti-PD-1 antibody combinations. Liver Cancer 10:320–329. https://doi.org/10.1159/000514313
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Ethical standard
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This was a retrospective and single-center observational study; the protocol was approved by Kyoto University Graduate School and Faculty of Medicine, Ethics Committee (approval code: R3013).
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The original online version of this article was revised due to a retrospective Open Access order.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Yoh, T., Ishii, T., Nishio, T. et al. A Conceptual Classification of Resectability for Hepatocellular Carcinoma. World J Surg 47, 740–748 (2023). https://doi.org/10.1007/s00268-022-06803-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-022-06803-7