|
1
|
Stulpinas R, Jakiunaite I, Sidabraite A, Rasmusson A, Zilenaite-Petrulaitiene D, Strupas K, Laurinavicius A, Gulla A. Low CD8+ Density Variation and R1 Surgical Margin as Independent Predictors of Early Post-Resection Recurrence in HCC Patients Meeting Milan Criteria. Curr Oncol 2024; 31:5344-5353. [PMID: 39330022 PMCID: PMC11431076 DOI: 10.3390/curroncol31090394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/04/2024] [Accepted: 09/08/2024] [Indexed: 09/28/2024] Open
Abstract
Our study included 41 patients fulfilling the Milan criteria preoperatively and aimed to identify individuals at high risk of post-resection HCC relapse, which occurred in 18 out of 41 patients (43.9%), retrospectively. We analyzed whole slide images of CD8 immunohistochemistry with automated segmentation of tissue classes and detection of CD8+ lymphocytes. The image analysis outputs were subsampled using a hexagonal grid-based method to assess spatial distribution of CD8+ lymphocytes with regards to the epithelial edges. The CD8+ lymphocyte density indicators, along with clinical, radiological, post-surgical and pathological variables, were tested to predict HCC relapse. Low standard deviation of CD8+ density along the tumor edge and R1 resection emerged as independent predictors of shorter recurrence-free survival (RFS). In particular, patients presenting with both adverse predictors exhibited 100% risk of relapse within 200 days. Our results highlight the potential utility of integrating CD8+ density variability and surgical margin to identify a high relapse-risk group among Milan criteria-fulfilling HCC patients. Validation in cohorts with core biopsy could provide CD8+ distribution data preoperatively and guide preoperative decisions, potentially prioritizing liver transplantation for patients at risk of incomplete resection (R1) and thereby improving overall treatment outcomes significantly.
Collapse
Affiliation(s)
- Rokas Stulpinas
- Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, 08406 Vilnius, Lithuania
| | - Ieva Jakiunaite
- Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Agne Sidabraite
- Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Allan Rasmusson
- Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, 08406 Vilnius, Lithuania
| | - Dovile Zilenaite-Petrulaitiene
- Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, 08406 Vilnius, Lithuania
- Institute of Informatics, Faculty of Mathematics and Informatics, Vilnius University, 03225 Vilnius, Lithuania
| | - Kestutis Strupas
- Institute of Clinical Medicine, Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Vilnius University, 01513 Vilnius, Lithuania
| | - Arvydas Laurinavicius
- Institute of Biomedical Sciences, Department of Pathology and Forensic Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, 08406 Vilnius, Lithuania
| | - Aiste Gulla
- Institute of Clinical Medicine, Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Vilnius University, 01513 Vilnius, Lithuania
- Department of Surgery, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA
| |
Collapse
|
|
2
|
Endo Y, Munir MM, Woldesenbet S, Katayama E, Ratti F, Marques HP, Cauchy F, Lam V, Poultsides GA, Kitago M, Popescu I, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Gleisner A, Hugh T, Aldrighetti L, Shen F, Endo I, Pawlik TM. Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score. Ann Surg Oncol 2023; 30:6581-6589. [PMID: 37432523 DOI: 10.1245/s10434-023-13825-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 06/14/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND We sought to examine the prognostic impact of margin width at time of hepatocellular carcinoma (HCC) resection relative to the alpha-feto protein tumor burden score (ATS). PATIENTS AND METHODS Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from a multi-institutional database. The impact of margin width on overall survival and recurrence-free survival was examined relative to ATS using univariable and multivariable analyses. RESULTS Among 782 patients with HCC who underwent resection, median ATS was 6.5 [interquartile range (IQR) 4.3-10.2]. Most patients underwent R0 resection (n = 613, 78.4%); among patients who had an R0 resection, 325 (41.6%) had a margin width > 5 mm while 288 (36.8%) had a 0-5 mm margin width. Among patients with high ATS, an increasing margin width was associated with incrementally better overall and recurrence-free survival. In contrast, among patients with low ATS, margin width was not associated with long-term outcomes. On multivariable Cox regression analysis, each unit increase in ATS was independently associated with a 7% higher risk of death [hazard ratio (HR) 1.07; 95% confidence interval (CI) 1.03-1.11, p < 0.001]. While the incidence of early recurrence was not associated with margin width among patients with low ATS, wider margin width was associated with an incrementally lower incidence of early recurrence among patients with high ATS. CONCLUSION ATS, an easy-to-use composite tumor-related metric, was able to risk stratify patients following resection of HCC relative to overall survival and recurrence-free survival. The therapeutic impact of resection margin width had a variable impact on long-term outcomes relative to ATS.
Collapse
Affiliation(s)
- Yutaka Endo
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Muhammad Musaab Munir
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Selamawit Woldesenbet
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Erryk Katayama
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | | | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | | | - Ana Gleisner
- Department of Surgery, University of Colorado, Denver, CO, USA
| | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | | | - Feng Shen
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
| |
Collapse
|
|
3
|
Park Y, Han HS, Yoon YS, Yoon CJ, Lee HW, Lee B, Kang M, Kim J, Cho JY. Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation: A Retrospective Cohort Study with Propensity Score-Matched Analysis. Cancers (Basel) 2023; 15:4745. [PMID: 37835438 PMCID: PMC10572041 DOI: 10.3390/cancers15194745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Although radiofrequency ablation (RFA) is a well-established locoregional treatment modality for hepatocellular carcinoma (HCC), the optimal strategy to handle local recurrence after ablation is still debated. This study aims to investigate the role of salvage hepatectomy (SH) as a rescue therapy for recurrent HCC after RFA. MATERIALS AND METHODS Between January 2004 and December 2020, 1161 patients were subject to surgical resection for HCC. Among them, 47 patients who underwent SH for local recurrence after ablation were retrospectively analyzed and compared to a propensity score-matched group of controls (n = 47) who received primary hepatectomy (PH). Short-term and long-term outcomes were analyzed between the two groups. RESULTS After matching, operation time, intraoperative blood loss, postoperative hospital stay, and postoperative morbidity rates showed no statistically significant difference. Tumors in the SH group were associated with poor differentiation (SH 9 (19.1%) vs. PH 1 (2.1%), p < 0.001). The 5-year disease-free survival rates (31.6% vs. 73.4%, p < 0.001) and overall survival rates (80.3% vs. 94.2%, p = 0.047) were significantly lower in the SH group. In multivariable analysis, less extensive resection compared to the initial plan (hazard ratio (HR) 4.68, p = 0.024), higher grade (HR 5.38, P < 0.001), negative but close (<0.1 cm) resection margin (HR 22.14, p = 0.007), and R1 resection (HR 3.13, p = 0.006) were significant predictors for recurrence. CONCLUSIONS SH for recurrent tumors after ablation showed safety and effectiveness equivalent to primary resection. As recurrent tumors show a higher grade and more aggressive behavior, more extensive resections with wide surgical margins are necessary to prevent recurrence.
Collapse
Affiliation(s)
- Yeshong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Chang Jin Yoon
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - MeeYoung Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Jinju Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, Republic of Korea; (Y.P.); (Y.-S.Y.); (J.K.)
| |
Collapse
|
|
4
|
Ke Q, Guo Z, He J, Lai Z, Xin F, Zeng Y, Wang L, Liu J. Resection Margin Width Does Not Influence the Prognosis of Solitary Hepatocellular Carcinoma After Anatomic Resection: A Real-World Study from China. J Hepatocell Carcinoma 2023; 10:1353-1365. [PMID: 37605757 PMCID: PMC10440086 DOI: 10.2147/jhc.s420828] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 07/29/2023] [Indexed: 08/23/2023] Open
Abstract
PURPOSE The influence of resection margin (RM) width on the prognosis of solitary hepatocellular carcinoma (HCC) following anatomical resection (AR) has yet to be determined. Therefore, we conducted a real-world study to identify the optimal RM width and assess its impact on the outcomes of solitary HCC patients undergoing AR. METHODS The data pertaining to patients diagnosed with solitary HCC who underwent AR between December 2012 and December 2015 were retrospectively collected. The optimal cutoff value for the width of the RM was determined using X-tile software. The Kaplan-Meier method was utilized to compare the overall survival (OS) and disease-free survival (DFS) between the narrow and wide RM groups. Additionally, propensity score matching (PSM) was performed to minimize potential bias in the data. RESULTS Of the 1033 patients who met the inclusion criteria, 293 (28.4%) were categorized into the narrow RM group (≤4 mm) and 740 (71.6%) into the wide RM group (> 4mm). Before and after PSM, there were no significant differences in OS and DFS between the two groups (before PSM: OS, HR=0.78, P=0.071; DFS, HR=0.95, P=0.620; after PSM: OS, HR=0.77, P=0.150; DFS, HR=0.90, P=0.470). Multivariate analysis demonstrated that RM width was not an independent risk factor for DFS and OS both before and after PSM (all P>0.05). However, subgroup analyses revealed that patients with ALBI grade 1, absence of cirrhosis, and AJCC stage II significantly benefited from wide RM in OS (all P< 0.05). Similarly, patients without HBV infection and absence of cirrhosis also exhibited significant benefits from wide RM in DFS (both P< 0.05). CONCLUSION In patients with solitary HCC undergoing AR, the width of the RM does not appear to have a significant impact on their prognosis. However, in certain selected patients, a wider RM may confer benefits.
Collapse
Affiliation(s)
- Qiao Ke
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
| | - Zhiting Guo
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, People’s Republic of China
| | - Jian He
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
| | - Zisen Lai
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
| | - Fuli Xin
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
| | - Yongyi Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
| | - Lei Wang
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, People’s Republic of China
| |
Collapse
|
|
5
|
Chao JS, Zhu Q, Chen DS, Chen GM, Xie XQ, Liu AQ, Zhao SL, Sun HC. Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2022; 21:551-558. [PMID: 35000845 DOI: 10.1016/j.hbpd.2021.12.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 12/13/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.
Collapse
Affiliation(s)
- Jia-Shuo Chao
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Qi Zhu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - De-Sheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Gui-Ming Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Xue-Qian Xie
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Ai-Qun Liu
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Sen-Lin Zhao
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Hong-Cheng Sun
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
| |
Collapse
|
|
6
|
Zhou JM, Zhou CY, Chen XP, Zhang ZW. Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: A prospective cohort study. World J Gastrointest Oncol 2021; 13:2190-2202. [PMID: 35070051 PMCID: PMC8713310 DOI: 10.4251/wjgo.v13.i12.2190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/05/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types.
AIM To explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI.
METHODS A total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group.
RESULTS In the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491).
CONCLUSION For patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.
Collapse
Affiliation(s)
- Jiang-Min Zhou
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Chen-Yang Zhou
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xiao-Ping Chen
- Translational Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| |
Collapse
|
|
7
|
Lim C, Goumard C, Casellas-Robert M, Lopez-Ben S, Lladó L, Busquets J, Salloum C, Albiol-Quer MT, Castro-Gutiérrez E, Rosmorduc O, Feray C, Ramos E, Figueras J, Scatton O, Azoulay D. Impact on Oncological Outcomes and Intent-to-Treat Survival of Resection Margin for Transplantable Hepatocellular Carcinoma in All-Comers and in Patients with Cirrhosis: A Multicenter Study. World J Surg 2021; 44:1966-1974. [PMID: 32095855 DOI: 10.1007/s00268-020-05424-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The outcomes of liver resection (LR) with a narrow margin in patients with transplantable hepatocellular carcinoma (HCC) have not been studied. The aim was to assess whether narrow margin following up-front LR impacts the incidence, timing, pattern, and transplantability of tumor recurrence in patients with initially transplantable HCC. METHODS All initially transplantable HCC patients undergoing hepatectomy with either narrow (<10 mm) or wide (≥10 mm) margins from 2007 to 2016 at four Western university centers were compared in terms of recurrence, transplantability of recurrence, recurrence-free survival (RFS), and intention-to-treat overall survival (ITT-OS). Independent predictors of non-transplantability of recurrence were assessed. RESULTS This study included 187 patients (narrow group, n = 107 vs. wide group, n = 80). Recurrence was significantly more frequent in the narrow margin group (44% vs. 26%; p = 0.01) with a shorter RFS (p = 0.03). The transplantability of recurrence and ITT-OS were, however, not different between the two groups. The presence of satellite nodules on the resected specimens emerged as the sole independent predictor of non-transplantability of tumor recurrence. The stratification of the analysis according to the presence of cirrhosis achieved essentially the same results as in the whole study population. CONCLUSIONS Narrow margin was associated with a higher tumor recurrence rate and a shorter RFS for patients with initially transplantable HCC. However, transplantability of recurrence and long-term ITT-OS were not impaired.
Collapse
Affiliation(s)
- Chetana Lim
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpétrière Hospital, Paris, France
| | - Claire Goumard
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpétrière Hospital, Paris, France
| | - Margarida Casellas-Robert
- Department of Hepato-Biliary and Pancreatic Surgery, Hospital Universitari Dr. Josep Trueta, Girona, Catalonia, Spain
| | - Santiago Lopez-Ben
- Department of Hepato-Biliary and Pancreatic Surgery, Hospital Universitari Dr. Josep Trueta, Girona, Catalonia, Spain
| | - Laura Lladó
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, CIBERehd., Barcelona, Catalonia, Spain
| | - Juli Busquets
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, CIBERehd., Barcelona, Catalonia, Spain
| | - Chady Salloum
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Paul Brousse Hospital, Villejuif, France
| | - Maria Teresa Albiol-Quer
- Department of Hepato-Biliary and Pancreatic Surgery, Hospital Universitari Dr. Josep Trueta, Girona, Catalonia, Spain
| | - Ernest Castro-Gutiérrez
- Department of Hepato-Biliary and Pancreatic Surgery, Hospital Universitari Dr. Josep Trueta, Girona, Catalonia, Spain
| | - Olivier Rosmorduc
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpétrière Hospital, Paris, France
| | - Cyrille Feray
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Paul Brousse Hospital, Villejuif, France
| | - Emilio Ramos
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, CIBERehd., Barcelona, Catalonia, Spain
| | - Joan Figueras
- Department of Hepato-Biliary and Pancreatic Surgery, Hospital Universitari Dr. Josep Trueta, Girona, Catalonia, Spain
| | - Olivier Scatton
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpétrière Hospital, Paris, France
| | - Daniel Azoulay
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Paul Brousse Hospital, Villejuif, France. .,Department of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. .,Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Avenue Paul Vaillant Couturier, 94000, Villejuif, France.
| |
Collapse
|
|
8
|
Tsilimigras DI, Sahara K, Moris D, Hyer JM, Paredes AZ, Bagante F, Merath K, Farooq AS, Ratti F, Marques HP, Soubrane O, Azoulay D, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Guglielmi A, Hugh T, Aldrighetti L, Endo I, Pawlik TM. Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: An International Multi-Institutional Analysis. J Gastrointest Surg 2020; 24:1552-1560. [PMID: 31243714 DOI: 10.1007/s11605-019-04275-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 05/17/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1 cm) versus narrow (< 1 cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy. METHODS Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins. RESULTS Among 404 patients, median patient age was 66 years (IQR: 58-73). Most patients (n = 326, 80.7%) had surgical margin < 1 cm, while 78 (19.3%) patients had a > 1 cm margin. The majority of patients had early recurrences (< 24 months) in both margin width groups (< 1 cm: 70.3% vs > 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic (< 1 cm: 77% vs > 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin < 1 cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin > 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: < 1 cm: 49.2% vs > 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin < 1 cm (86.7% vs 47.3%, p = 0.017). On multivariable analysis, margin > 1 cm remained protective against recurrence (HR = 0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09-4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence. CONCLUSION Resection margins > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.
Collapse
Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Kota Sahara
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Dimitrios Moris
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - J Madison Hyer
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Anghela Z Paredes
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Fabio Bagante
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Katiuscha Merath
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Ayesha S Farooq
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Daniel Azoulay
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | | | - Tom Hugh
- Department of Surgery, The University of Sydney, School of Medicine, Sydney, Australia
| | | | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.
| |
Collapse
|
|
9
|
D'Souza AM, Towbin AJ, Gupta A, Alonso M, Nathan JD, Bondoc A, Tiao G, Geller JI. Clinical heterogeneity of pediatric hepatocellular carcinoma. Pediatr Blood Cancer 2020; 67:e28307. [PMID: 32307899 DOI: 10.1002/pbc.28307] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 02/11/2020] [Accepted: 03/16/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is often a chemoresistant neoplasm with a poor prognosis. Pediatric HCC may reflect unique biological and clinical heterogeneity. PROCEDURE An IRB-approved retrospective institutional review of patients with HCC treated between 2004 and 2015 was undertaken. Clinical, radiographic, and histologic data were collected from all patients. RESULTS Thirty-two patients with HCC, median age 11.5 years (range 1-20) were identified. Seventeen patients had a genetic or anatomic predisposition. Histology was conventional HCC (25) and fibrolamellar HCC (7). Evans staging was 1 (12); 2 (1); 3 (10); 4 (9). Sixteen patients underwent resection at diagnosis and five patients after neoadjuvant chemotherapy. Surgical procedures included liver transplantation (LT, 11), hemihepatectomy (9), and segmentectomy (1). Eighteen patients had medical therapy (13 neoadjuvant, 5 adjuvant). Most common initial medical therapy included sorafenib alone (7) and cisplatin/doxorubicin-based therapy (8). Overall, 14 (43.8%) patients survived with a median follow-up of 58.8 months (range 26.5-157.6). Cause of death was most often linked to lack of primary tumor surgery (11). Of the survivors, Evans stage was 1 (11), 2 (1), and 3 (2, both treated with LT). Four of 18 patients (22%) who received medical therapy, 8 of 17 patients with a predisposition (47%), and 14 of 21 patients (66%) who underwent surgery remain alive. CONCLUSIONS Genetic and anatomic predisposing conditions were seen in over half of this cohort. Evans stage 1 or 2 disease was linked to improved survival. LT trended toward improved survival. Use of known chemotherapy agents may benefit a smaller group of pediatric HCC and warrants formal prospective study through cooperative group trials.
Collapse
Affiliation(s)
- Amber M D'Souza
- Division of Pediatric Hematology/Oncology, University of Illinois College of Medicine at Peoria, Peoria, Illinois
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Anita Gupta
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Maria Alonso
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jaimie D Nathan
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alex Bondoc
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Greg Tiao
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - James I Geller
- Division of Pediatric Hematology/Oncology, University of Illinois College of Medicine at Peoria, Peoria, Illinois
| |
Collapse
|
|
10
|
Wang H, Yu H, Qian YW, Cao ZY, Wu MC, Cong WM. Impact of Surgical Margin on the Prognosis of Early Hepatocellular Carcinoma (≤5 cm): A Propensity Score Matching Analysis. Front Med (Lausanne) 2020; 7:139. [PMID: 32478080 PMCID: PMC7232563 DOI: 10.3389/fmed.2020.00139] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 03/30/2020] [Indexed: 12/11/2022] Open
Abstract
Aim: The influence of surgical margin on the prognosis of patients with early solitary hepatocellular carcinoma (HCC) (≤5 cm) is undetermined. Methods: The data of 904 patients with early solitary HCC who underwent liver resection were collected for recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was performed to balance the potential bias. Results: Log-rank tests showed that 2 mm was the best cutoff value to discriminate the prognosis of early HCC. Liver resection with a >2 mm surgical margin distance (wide-margin group) led to better 5-year RFS and OS rate compared with liver resection with a ≤2 mm surgical margin distance (narrow-margin group) among patients both before (RFS: 59.1% vs. 39.6%, P < 0.001; OS: 85.3% vs. 73.7%, P < 0.001) and after PSM (RFS: 56.3% vs. 41.0%, P < 0.001; OS: 83.0% vs. 75.0%, P = 0.010). Subgroup analysis showed that a wide-margin resection significantly improved the prognosis of patients with microvascular invasion (RFS: P < 0.001; OS: P = 0.001) and patients without liver cirrhosis (RFS: P < 0.001; OS: P = 0.001) after PSM. Multivariable Cox regression analysis revealed that narrow-margin resection is associated with poorer RFS [hazard ratio (HR) = 1.781, P < 0.001), OS (HR = 1.935, P < 0.001], and early recurrence (HR = 1.925, P < 0.001). Conclusions: A wide-margin resection resulted in better clinical outcomes than a narrow-margin resection among patients with early solitary HCC, especially for those with microvascular invasion and without cirrhosis. An individual strategy of surgical margin should be formulated preoperation according to both tumor factors and background liver factors.
Collapse
Affiliation(s)
- Han Wang
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hua Yu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - You-Wen Qian
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Zhen-Ying Cao
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| |
Collapse
|
|
11
|
Bartsch F, Baumgart J, Hoppe-Lotichius M, Straub BK, Heinrich S, Lang H. Intrahepatic cholangiocarcinoma - influence of resection margin and tumor distance to the liver capsule on survival. BMC Surg 2020; 20:61. [PMID: 32252724 PMCID: PMC7137203 DOI: 10.1186/s12893-020-00718-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 03/17/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is often diagnosed in advanced stage. Aim of this study was to analyse the influence of resection margins and tumor distance to the liver capsule on survival and recurrence in a single center with a high number of extended resections. METHODS From January 2008 to June 2018 data of all patients with ICC were collected and further analysed with Kaplan Meier Model, Cox regression or Chi2 test for categorical data. RESULTS Out of 210 included patients 150 underwent curative intended resection (71.4%). Most patients required extended resections (n = 77; 51.3%). R0-resection was achieved in 131 patients (87.3%) with minimal distances to the resection margin > 1 cm in 22, 0.5-1 cm in 11, 0.1-0.5 cm in 49 patients, and < 0.1 cm in 49 patients. Overall survival (OS) for margins > 0.5 cm compared to 0.5-0.1 cm or R1 was better, but without reaching significance. All three groups had significantly better OS compared to the irresectable group. Recurrence-free survival (RFS) was also better in patients with a margin > 0.5 cm than in the < 0.5-0.1 cm or the R1-group, but even without reaching significance. Different distance to the liver capsule significantly affected OS, but not RFS. CONCLUSIONS Wide resection margins (> 0.5 cm) should be targeted but did not show significantly better OS or RFS in a cohort with a high percentage of extended resections (> 50%). Wide margins, narrow margins and even R1 resections showed a significant benefit over the irresectable group. Therefore, extended resections should be performed, even if only narrow margins can be achieved.
Collapse
Affiliation(s)
- Fabian Bartsch
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Janine Baumgart
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Maria Hoppe-Lotichius
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Beate K Straub
- Department of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Stefan Heinrich
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
| |
Collapse
|
|
12
|
Shen A, Liu M, Zheng D, Chen Q, Wu Z. Adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2020; 44:142-154. [PMID: 31303533 DOI: 10.1016/j.clinre.2019.06.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/30/2019] [Accepted: 06/05/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Microvascular invasion (MVI) has been associated with a poor prognosis for hepatocellular carcinoma (HCC) patients. This study aimed to evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy for HCC with MVI. METHODS An online search on Embase and Ovid MEDLINE(R) was conducted to identify the appropriate articles published prior to March 11, 2019. The primary endpoint was the overall survival (OS) of patients treated using adjuvant TACE after hepatectomy (HTAT) versus hepatectomy (HT) alone for HCC with MVI. The secondary endpoints were disease-free survival (DFS) and safety. RESULTS Seven studies with 1869 patients were included in this analysis. Meta-analyses demonstrated that HTAT was superior to HT in OS (Hazard Ratio [HR]: 0.67, 95%CI: 0.58-0.77, P<0.001) and DFS (HR: 0.71, 95%CI: 0.62-0.81, P<0.001) for treating HCC with MVI. Subgroup analysis revealed that for early-stage HCC, HTAT was associated with longer OS (P=0.009) and DFS (P=0.066) as compared with HT. For HCC larger than 5cm, HTAT also prolonged the DFS (P=0.008) of patients, but the difference in OS was not statistically significant (P=0.266). Adjuvant TACE commonly caused nausea and vomiting, liver dysfunction, leucopenia, pain, and fever. CONCLUSIONS Adjuvant TACE after hepatectomy is effective and safe for patients with HCC accompanied by MVI. However, the benefit of adjuvant TACE in patients who have HCC with a diameter >5cm is not clear. Further randomized controlled studies are warranted to test these conclusions.
Collapse
Affiliation(s)
- Ai Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Hepatobiliary and Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
| | - Miao Liu
- Gastrointestinal Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
| | - Daofeng Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Qingsong Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Zhongjun Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| |
Collapse
|
|
13
|
Sellier C, Carabalona J, Hahn H, Dvm EG, Bismuth C. Use of a cavitron ultrasonic surgical aspirator for parenchyma-sparing and complex liver resections in dogs. Vet Surg 2020; 49:800-810. [PMID: 32073180 DOI: 10.1111/vsu.13401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 01/21/2020] [Accepted: 01/25/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To report the clinical use of a cavitron ultrasonic surgical aspirator (CUSA) for the resection of hepatic lesions in dogs. STUDY DESIGN Clinical prospective study. ANIMALS Eleven client-owned dogs. METHODS Dogs requiring a hepatic nodulectomy, segmentectomy, and/or a lobectomy (including complex lobectomies) were enrolled. The number and location of procedures, blood loss, duration of surgery, and short-term complications were recorded. RESULTS Dogs underwent a mean of 2.3 ± 1.1 procedures. All masses were amenable to surgical excision regardless of their location and their relationship with major hepatic vessels. Dogs lost a median of 77 mL of blood (9.9-161), which corresponded to 4.3% of blood volume (0.8%-23.2%). The dog with the highest blood loss survived without requiring transfusion. The median duration of all CUSA procedures was 33.5 minutes (15-82). Short-term outcomes were assessed for the first 15 days, during which two complications were diagnosed. Cholangiohepatitis was diagnosed in one dog and resolved after medical management, and another dog developed necrotic pancreatitis and died. CONCLUSION Liver parenchyma-sparing nodulectomies and segmentectomies and liver lobectomies including complex lobectomies were achieved with a CUSA in all dogs. CLINICAL SIGNIFICANCE Use of a CUSA can be considered as an alternative for the removal of hepatic lesions in dogs.
Collapse
Affiliation(s)
- Clément Sellier
- Department of Surgery, Small Animal, Veterinary Hospital Frégis, Arcueil, France
| | - Julien Carabalona
- Department of Surgery, Small Animal, Veterinary Hospital Frégis, Arcueil, France
| | - Harriet Hahn
- Department of Diagnostic Imaging, Small Animal, Veterinary Hospital Frégis, Arcueil, France
| | - Eymeric Gomes Dvm
- Department of Diagnostic Imaging, Small Animal, Veterinary Hospital Frégis, Arcueil, France
| | - Camille Bismuth
- Department of Surgery, Small Animal, Veterinary Hospital Frégis, Arcueil, France
| | | |
Collapse
|
|
14
|
Sakon M, Kobayashi S, Wada H, Eguchi H, Marubashi S, Takahashi H, Akita H, Gotoh K, Yamada D, Asukai K, Hasegawa S, Ohue M, Yano M, Nagano H. "Logic-Based Medicine" Is More Feasible than "Evidence-Based Medicine" in the Local Treatment for Hepatocellular Carcinoma. Oncology 2020; 98:259-266. [PMID: 32045926 DOI: 10.1159/000505554] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 12/12/2019] [Indexed: 01/18/2023]
Abstract
The optimal type of surgery (e.g., anatomic or non-anatomic resection) or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is still under debate despite numerous comparative studies based on overall survival. This debate continues not only because these endpoints are influenced by non-surgical factors, such as liver function, but because the definition of non-anatomic resection for HCC has remained unclear. The optimal surgery could be logically determined based on the mechanism of local intrahepatic metastasis, that is, the drainage of tumour blood flow (TBF), because HCC spreads locally through tumour blood flowing to the peri-tumourous liver parenchyma. Since TBF is clearly demonstrated by CT scan under hepatic arteriography, the surgical margin can be determined individually based on the drainage of TBF without deteriorating local curability. Controversy regarding RFA and surgery does not result from the curability of treatment itself but from the lack of scientific evidence on safety margins. Based on proper concepts and self-evident truths, an algorithm of loco-regional treatment for HCC is proposed.
Collapse
Affiliation(s)
- Masato Sakon
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan,
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Shigeru Marubashi
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, Fukushima Medical University, Fukushima, Japan
| | - Hidenori Takahashi
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Daisaku Yamada
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kei Asukai
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | | | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masahiko Yano
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Yamaguchi, Japan
| |
Collapse
|
|
15
|
Gruttadauria S, Pagano D, Corsini LR, Cintorino D, Li Petri S, Calamia S, Seidita A, di Francesco F. Impact of margin status on long-term results of liver resection for hepatocellular carcinoma: single-center time-to-recurrence analysis. Updates Surg 2019; 72:109-117. [PMID: 31625024 DOI: 10.1007/s13304-019-00686-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/07/2019] [Indexed: 02/06/2023]
Abstract
Occult metastasis from the initial tumor and a de novo second primary hepatocellular carcinoma (HCC) were recognized as the main causes for the onset of early and late HCC recurrence, after liver resection (LR). This study aims to compare the time to recurrence after LR for HCC in which a margin ≤ 1 mm or > 1 mm was achieved. A single-center retrospective study involving 256 patients was conducted from June 2005 to June 2019. HCC patients resected with a radical surgical approach were investigated and stratified into groups A (resection margins ≤ 1 mm) and B (> 1 mm), as measured on final pathologic assessment. Kaplan-Meier estimators were used to estimate the probability of recurrence, and the log-rank test was used to compare groups. Uni- and multivariable (stepwise) Cox regression models were used to assess the effect of several HCC pathological characteristics. Twenty patients were excluded for the presence of microscopic tumor invasion at pathologic analysis (R1); 236 patients underwent radical (R0) LR, and were included in the study and divided into group A (n = 61, 26%), and group B (n = 175, 74%). No differences between the two groups were detected regarding: epidemiology, tumor characteristics, type of LR, and follow-up. The estimated probability of recurrence for group A and group B at 12 and 24 months was 27% and 38%, and, 33% and 46%, respectively. Univariate and multivariable Cox regression model estimates showed that tumor grading (HR 2.1, 95% CI 1.2-3.4, p = 0.006), number of nodules (HR 1.2, 95% CI 1.0-1.4, p = 0.015), and extension of the resection (HR 1.8, 95% CI 1.0-1.1, p = 0.047) were independent risk factors for HCC recurrence, with no significant effect of margin status on time to recurrence. A R0 approach that considers a margin of resection > 1 mm does not improve the likelihood of HCC recurrence. Otherwise, our experience confirms that biologic tumor characteristics are the principal factors predictive of local and systemic recurrence.
Collapse
Affiliation(s)
- Salvatore Gruttadauria
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy.
- Department of Surgery, University of Catania, Catania, Italy.
| | - Duilio Pagano
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| | - Lidia R Corsini
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
- Department of Oncology, A.O.U.P. P. Giaccone, Palermo, Italy
| | - Davide Cintorino
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| | - Sergio Li Petri
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| | - Sergio Calamia
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| | - Aurelio Seidita
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| | - Fabrizio di Francesco
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Via E. Tricomi 5, 90127, Palermo, Italy
| |
Collapse
|
|
16
|
Lim C, Salloum C, Lahat E, Sotirov D, Eshkenazy R, Shwaartz C, Azoulay D. Impact of narrow margin and R1 resection for hepatocellular carcinoma on the salvage liver transplantation strategy. An intention-to-treat analysis. HPB (Oxford) 2019; 21:1295-1302. [PMID: 30833187 DOI: 10.1016/j.hpb.2019.02.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/27/2019] [Accepted: 02/04/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND No studies have investigated whether narrow margin is a risk factor for hepatocellular carcinoma recurrence outside transplantability criteria. The objective was to assess on an intent-to-treat (ITT) basis whether hepatectomy with narrow margin affects the outcomes in patients enrolled in the salvage liver transplantation (LT) strategy. METHODS From 2007 to 2016, patients enrolled in the salvage LT strategy were divided into 2 groups: narrow (<10 mm) vs. wide (≥10 mm) margin groups. R1 resection was defined as positive histologic margin involvement. Recurrence rate, transplantability rate of recurrence and ITT overall survival (ITT-OS) were evaluated. RESULTS A total of 81 patients were studied: 43 patients with narrow margin and 38 with wide margin. The recurrence rates, pattern and delay of recurrence, transplantability following recurrence, and ITT-OS were similar between the two groups. These results were maintained when comparing patients with R1 resection to those with R0 resection. CONCLUSION On an ITT basis, hepatectomy with narrow margin or R1 resection did not impair the transplantability of recurrence and survival of patients enrolled in the salvage LT strategy. Narrow margin and even R1 resection following hepatectomy in the setting of salvage LT strategy should not be the basis for altering the strategy.
Collapse
Affiliation(s)
- Chetana Lim
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil, France
| | - Chady Salloum
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil, France
| | - Eylon Lahat
- Department of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dobromir Sotirov
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil, France
| | - Rony Eshkenazy
- Department of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Chaya Shwaartz
- Department of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Daniel Azoulay
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil, France; Department of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| |
Collapse
|
|
17
|
Donadon M, Terrone A, Procopio F, Cimino M, Palmisano A, Viganò L, Del Fabbro D, Di Tommaso L, Torzilli G. Is R1 vascular hepatectomy for hepatocellular carcinoma oncologically adequate? Analysis of 327 consecutive patients. Surgery 2019; 165:897-904. [PMID: 30691871 DOI: 10.1016/j.surg.2018.12.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/23/2018] [Accepted: 12/04/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND R1 vascular resection for liver tumors was introduced in the early twenty-first century. However, its oncologic adequacy remains controversial. The aim of this study was to determine the oncologic adequacy of R1 vascular hepatectomy in hepatocellular carcinoma patients. METHODS A prospective cohort of patients with hepatocellular carcinoma resected between the years 2005 and 2015 was reviewed. R0 was any resection with a minimum 1 mm of negative margin. R1 vascular was any resection with tumor exposure attributable to the detachment from major intrahepatic vessel. R1 parenchymal was any resection with tumor exposure at parenchymal margin. The end points were the calculation of the local recurrence of R0, R1 parenchymal, and R1 vascular hepatectomy and their prognostic significances. RESULTS We analyzed 327 consecutive patients with 532 hepatocellular carcinoma and 448 resection areas. We found that 205 (63%) resulted R0, 56 (17%) resulted R1 parenchymal, 50 (15%) resulted R1 vascular, and 16 (5%) resulted both R1 parenchymal and R1 vascular. After a median follow-up of 33.5 months (range 6.1-107.6), the 5-year overall survival rates were 54%, 30%, 65%, and 36%, respectively for R0, R1 parenchymal, R1 vascular, and R1 parenchymal + R1 vascular (P = .031). Local recurrence rates were 3%, 14%, 4%, and 19%, respectively for R0, R1 parenchymal, R1 vascular, and R1 parenchymal + R1 vascular (P = .001) per patient, and 4%, 4%, 12%, and 18%, respectively for R0, R1 vascular, R1 parenchymal, and R1 parenchymal + R1 vascular (P = .001) per resection area. At multivariate analysis R1 parenchymal and R1 vascular + R1 parenchymal were independent detrimental factors. CONCLUSION R1 vascular hepatectomy for hepatocellular carcinoma is not associated with increased local recurrence or decreased survival. Thus, detachment of hepatocellular carcinoma from intrahepatic vessels should be considered oncologically adequate.
Collapse
Affiliation(s)
- Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy; Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Alfonso Terrone
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Matteo Cimino
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Angela Palmisano
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy; Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Humanitas University and Research Hospital, Rozzano, Milan, Italy; Department of Pathology, Humanitas University and Research Hospital, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Research Hospital, Rozzano, Milan, Italy; Humanitas University and Research Hospital, Rozzano, Milan, Italy.
| |
Collapse
|
|
18
|
D'Souza AM, Shah R, Gupta A, Towbin AJ, Alonso M, Nathan JD, Bondoc A, Tiao G, Geller JI. Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma. Pediatr Blood Cancer 2018; 65:e27293. [PMID: 29968976 DOI: 10.1002/pbc.27293] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 05/13/2018] [Accepted: 05/30/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that is often chemoresistant. Complete surgical resection remains the mainstay of therapy. The role of liver transplantation (LT) in pediatric HCC is in evolution, as is the role of adjuvant chemotherapy for stage I disease. METHODS A retrospective review of patients < 18 years of age with completely resected HCC treated with surgical intervention alone at our institution from 2004 to 2015 was conducted. RESULTS Twelve patients with a median age of 12 years (range = 1-17; number of females = 7) with upfront resected HCC (Evans stage I) were identified. Four patients had HCC without identifiable risk factors (fibrolamellar-HCC = 2; early HCC arising in focal nodular hyperplasia = 1, well-differentiated [wd] HCC = 1). Four patients had early or wd-HCC in the context of portosystemic shunts (Abernethy = 2; mesocaval shunt and portal vein thrombosis = 2). Four patients had moderate to wd-HCC in the context of pre-existing liver disease with cirrhosis (progressive familial intrahepatic cholestasis type-2 = 2, alpha-1 antitrypsin deficiency = 1, Alagille syndrome = 1). Seven patients underwent LT (multifocal = 5; solitary = 2); five exceeded Milan criteria (MC) by imaging. Five patients underwent complete resection (segmentectomy = 2; hemihepatectomy = 3). Ten patients received no adjuvant chemotherapy. All patients are alive without evidence of disease with a median follow-up of 54.1 months (range = 28.1-157.7 months). CONCLUSIONS Pediatric and adolescent patients with upfront, completely resected HCC can be effectively treated without chemotherapy. LT should be considered for nonmetastatic HCC, especially in the context of pre-existing chronic liver disease, even when the tumor exceeds MC. Distinct pediatric selection criteria are needed to identify patients most suitable for LT.
Collapse
Affiliation(s)
- Amber M D'Souza
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Rachana Shah
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Anita Gupta
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Maria Alonso
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jaimie D Nathan
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alex Bondoc
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Greg Tiao
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - James I Geller
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| |
Collapse
|
|
19
|
Kim JM, Lee SH, Shin WY, Lee KY, Kim JM, Ahn SI. Intrahepatic recurrence of single nodular hepatocellular carcinoma after surgical resection: an analysis by segmental distribution. ANZ J Surg 2018; 88:E840-E844. [PMID: 30225975 PMCID: PMC6586000 DOI: 10.1111/ans.14824] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 06/26/2018] [Accepted: 07/20/2018] [Indexed: 12/19/2022]
Abstract
Background Intrahepatic recurrence is the major cause of management failure after surgical resection of hepatocellular carcinoma (HCC). In the present study, we analysed intrahepatic recurrence by HCC distribution using Couinaud's liver segments. Methods Recurrence proximity levels were defined with respect to primary tumour locations from Level LR (locoregional) to Level IV. Initial and recurrent tumours were compared with segmental distribution of their locations, and recurrence proximity levels were compared with initial tumour locations and disease‐free survival. Results Eighty‐five (58.2%) of 146 patients with single nodular HCC experienced intrahepatic recurrence after surgical resection with a mean disease‐free survival of 20.8 ± 21.1 months. Segmental distributions of initial and recurrent tumour locations were not significantly different (P > 0.05), and both were similar to the normal segmental volume distribution except segments S5, S6 and S8. Recurrences in proximity levels LR to IV were 11.1%, 34.9%, 25.4%, 21.4%, and 7.1%, respectively, and this distribution agreed well with theoretical proximity level distribution (P > 0.05). Disease‐free survivals for different recurrence levels were not different (P = 0.530). Conclusion Intrahepatic recurrences after surgical resection of single nodular HCC occurred evenly in the remnant liver, and the timing was independent of the proximity between initial and recurrent tumours. Prevention was found to be proportional to the amount of liver segments removed. Surgical plans should take this into consideration.
Collapse
Affiliation(s)
- Jin-Min Kim
- Department of Surgery, Inha University School of Medicine, Incheon, South Korea
| | - Seung-Hyun Lee
- Department of Surgery, Inha University School of Medicine, Incheon, South Korea
| | - Woo Young Shin
- Department of Surgery, Inha University School of Medicine, Incheon, South Korea
| | - Keon-Young Lee
- Department of Surgery, Inha University School of Medicine, Incheon, South Korea
| | - Jun Mee Kim
- Department of Pathology, Inha University School of Medicine, Incheon, South Korea
| | - Seung-Ik Ahn
- Department of Surgery, Inha University School of Medicine, Incheon, South Korea
| |
Collapse
|