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1
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He J, Liu Y, Xu H, Wei X, Chen M. Insights into the variations in microbial community structure during the development of periodontitis and its pathogenesis. Clin Oral Investig 2024; 28:675. [PMID: 39617812 DOI: 10.1007/s00784-024-06074-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 11/25/2024] [Indexed: 12/20/2024]
Abstract
OBJECTIVE To characterize the subgingival microbiota in subjects with stage I/II periodontitis (moderate periodontitis, MP), stage III/IV periodontitis (severe periodontitis, SP), and periodontal health (PH) at the same probing depth (PD) (shallow ≤ 3 mm, moderate 4-6 mm, or deep ≥ 7 mm), and to investigate the changes associated with probing depth progression. MATERIALS AND METHODS 100 subgingival plaque samples were collected from 50 subjects (16 MP, 17 SP and 17 PH), forming six groups: PHS (PH, shallow), MPS (MP, shallow), MPM (MP, moderate), SPS (SP, shallow), SPM (SP, moderate), and SPD (SP, deep). Samples were analyzed using high-throughput sequencing. RESULT The subgingival microbiome showed significant differences associated with both PD and periodontitis stage (p < 0.05). With increasing PD, alpha diversity initially increased and then decreased. Pathogenic genera like Fusobacterium, Filifactor, and Porphyromonas increased, while health-associated genera like Streptococcus and Haemophilus decreased. At shallow sites, the PHS, MPS, and SPS groups showed similar community structure. At moderate and deep sites, the SPM and SPD groups exhibited significant differences in community structure compared to the MPM group, with the SPM and SPD groups showing decreased abundances of Actinomyces and increased abundances of Treponema. The microbial co-networks in the SPD and SPM groups exhibited greater complexity and connectivity and were more resilient to random microbial or node removal. CONCLUSIONS The subgingival microbiome shows strong associations with PD and periodontitis stage. CLINICAL RELEVANCE Once periodontitis progresses to stage III/IV, reconstructing a healthy subgingival microbiome may be challenging, emphasizing the importance of early prevention.
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Affiliation(s)
- Junlin He
- Department of Periodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China
| | - Yefei Liu
- Department of Endodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China
| | - Hongzhen Xu
- Department of Prosthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China
| | - Xiaolin Wei
- Department of Endodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China.
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China.
| | - Meihua Chen
- Department of Periodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China.
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China.
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2
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Wang D, Xiao M, Wan ZM, Lin X, Li QY, Zheng SS. Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges. World J Gastrointest Surg 2023; 15:544-552. [PMID: 37206072 PMCID: PMC10190723 DOI: 10.4240/wjgs.v15.i4.544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 03/21/2023] [Indexed: 04/22/2023] Open
Abstract
Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.
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Affiliation(s)
- Di Wang
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Min Xiao
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Zhen-Miao Wan
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Xin Lin
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Qi-Yong Li
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Shu-Sen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
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3
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Liu H, Bai Y, Li F, Tian Z. Combined serum CXCL8, CXCL9 and CXCL13 tests for the prediction of microvascular invasion in hepatocellular carcinoma. Biomark Med 2023; 17:265-272. [PMID: 37218545 DOI: 10.2217/bmm-2023-0064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2023] Open
Abstract
Aim: This work is to explore the predictive and diagnostic value of chemokine C-X-C motif ligand 8 (CXCL8), CXCL9 and CXCL13 combined detections for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Materials & methods: A total of 82 HCC patients with MVI were recruited as the MVI group and 154 patients with non MVI were recruited as the non MVI group. Results: In HCC patients with MVI, CXCL8, CXCL9, CXCL13 levels were significantly elevated. Child-Pugh scores and serum α-fetoprotein level had positive correlation with CXCL8, CXCL9 and CXCL13 levels. The serum levels of CXCL8, 9 and 13 were effective in predicting MVI in HCC patients. Conclusion: CXCL8, CXCL9 and CXCL13 levels in HCC patients are valuable parameters in the prediction of MVI.
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Affiliation(s)
- Hong Liu
- Department of General Surgery, Fifth People's Hospital, No. 1215 Guangrui Road, Liangxi District, Wuxi, Jiangsu, 214007, China
| | - Yang Bai
- Department of Hepatobiliary Surgery, the 904th Hospital of Joint Logistic Support Force of PLA, No. 101 Xingyuan North Road, Wuxi, Jiangsu, 214044, China
| | - Fuli Li
- Department of General Surgery, Fifth People's Hospital, No. 1215 Guangrui Road, Liangxi District, Wuxi, Jiangsu, 214007, China
| | - Zhiqiang Tian
- Department of General Surgery, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, China
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4
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Zhang SR, Ma Y, Zhou B, Li GY, Chen P, Chen G. Case report and literature review: Isolated HCC- recurrence in gallbladder after curative resection. Front Surg 2023; 10:1115181. [PMID: 37181591 PMCID: PMC10174458 DOI: 10.3389/fsurg.2023.1115181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 04/04/2023] [Indexed: 05/16/2023] Open
Abstract
Background Liver resection (LR) is considered the mainstay treatment for eligible patients with hepatocellular carcinoma (HCC) and provides a 5-year overall survival (OS) of 60%-80%. However, the recurrence rate within five years after LR remains high, ranging from 40% to 70%. Recurrence in gallbladder after liver resection is extremely rare. Here, we present a case of isolated recurrence in gallbladder after curative resection of HCC and review the relevant literature. No similar cases have been reported before. Case presentation A 55-year-old male patient was diagnosed with HCC in 2009 and subsequently underwent a right posterior sectionectomy of the liver. In 2015, the patient underwent liver tumor radiofrequency ablation and three transarterial chemoembolization (TACE) procedures in succession for HCC recurrence. In 2019, a gallbladder lesion was detected by computed tomography (CT) without perceivable intrahepatic focus. We performed an en bloc resection of the gallbladder and hepatic segment IVb. The pathological biopsy suggested that the gallbladder tumor was moderately differentiated HCC. The patient survived more than 3 years in good condition, and there were no signs of tumor recurrence. Conclusions In patients with isolated gallbladder metastasis, if the lesion can be resected en bloc without remnants, surgery should be the preferred option. Both postoperative molecularly targeted drugs and immunotherapy are expected to improve the long-term prognosis.
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5
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L R, T I, Mpaw C, H M, G S. THE MANAGEMENT OF POST-TRANSPLANTATION RECURRENCE OF HEPATOCELLULAR CARCINOMA. Clin Mol Hepatol 2021; 28:1-16. [PMID: 34610652 PMCID: PMC8755475 DOI: 10.3350/cmh.2021.0217] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/03/2021] [Indexed: 11/15/2022] Open
Abstract
The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.
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Affiliation(s)
- Rajendran L
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Ivanics T
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Claasen Mpaw
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands
| | - Muaddi H
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Sapisochin G
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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Gupta S, Khan S, Kawka M, Gujjuri R, Chau I, Starling N, Cunningham D, Jiao LR, Gall T. Clinical utility of clonal origin determination in managing recurrent hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:1159-1167. [PMID: 34402366 DOI: 10.1080/17474124.2021.1967144] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Recurrence is the driving factor for reduced long-term survival in patients following resected hepatocellular carcinoma (HCC). Extensive research efforts have been conducted to understand the molecular processes precipitating disease recurrence. Modern genomic techniques have identified two distinct mechanisms for recurrent HCC (RHCC): Intrahepatic metastasis (IM-HCC); and multicentric origin (MO-HCC). Medline, EMBASE and Cochrane library were methodically searched for primary research articles in English with the aim of appraising existing literature on the identification of clonal origin of RHCC and its potential clinical utility. AREAS COVERED Molecular and next-generation sequencing techniques, when applied to clonal origin identification, yield superior accuracy than traditional clinicopathological criteria. Despite various treatment modalities, no optimal therapy has yet been identified for treating clonally differentiated RHCC. Patients with MO-HCC appear to experience improved long-term survival following re-treatment compared to their IM-HCC counterparts (91.7% vs 22.9% 5-year survival, p < 0.001). However, cautious interpretation is advised as heterogeneous classification criteria and small sample sizes restrict the generalizability of such findings. EXPERT OPINION Improved identification of clonal origin in RHCC may facilitate further research on RHCC treatment strategies and enable the development of novel therapeutic targets, potentially leading to individualized treatment approaches in the future.
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Affiliation(s)
- Shubham Gupta
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK
| | - Sikandar Khan
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK
| | - Michal Kawka
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK
| | - Rohan Gujjuri
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK
| | - Ian Chau
- Department Of Oncology And Surgery, The Royal Marsden Hospital, London, UK
| | - Naureen Starling
- Department Of Oncology And Surgery, The Royal Marsden Hospital, London, UK
| | - David Cunningham
- Department Of Oncology And Surgery, The Royal Marsden Hospital, London, UK
| | - Long R Jiao
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK.,Department Of Oncology And Surgery, The Royal Marsden Hospital, London, UK
| | - Tamara Gall
- Department of Medicine, Imperial College London, South Kensington Campus, London, UK.,Department Of Oncology And Surgery, The Royal Marsden Hospital, London, UK
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7
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Different Risk Factors for Early and Late Recurrence After Curative Resection of Hepatocellular Carcinoma. World J Surg 2021; 46:197-206. [PMID: 34533588 DOI: 10.1007/s00268-021-06308-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Factors of early and late recurrence after curative resection of hepatocellular carcinoma (HCC) may be different. The aim of this study was to identify clinical factors, including liver stiffness measurement (LSM), which are associated with HCC recurrence after curative resection. METHODS Patients who underwent preoperative LSM and primary curative resection for HCC between October 2015 and May 2018 were retrospectively reviewed, with 1 year as the cut-off between early and late recurrence. RESULTS Recurrence was observed in 42/149 (28.2%) patients over a median follow-up of 38.3 months (early recurrence: 10 [6.7%] patients; late recurrence: 32 [21.5%] patients). Multivariate analysis identified LSM (P = 0.026) and tumor size (P = 0.010) as the only factors that were significantly associated with recurrence-free survival. Compared with patients without recurrence, those with early recurrence had larger tumor size (P = 0.035) and those with late recurrence had higher LSM (P = 0.024). Receiver-operating characteristic analysis indicated that the optimal LSM cut-off value for predicting HCC recurrence was 7.4 kPa. CONCLUSION Tumor size was associated with early HCC recurrence after curative resection and LSM was associated with late recurrence. LSM cut-off of 7.4 kPa is recommended in predicting recurrence.
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8
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Anatomical resection is useful for the treatment of primary solitary hepatocellular carcinoma with predicted microscopic vessel invasion and/or intrahepatic metastasis. Surg Today 2021; 51:1429-1439. [PMID: 33564928 DOI: 10.1007/s00595-021-02237-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 01/02/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM). METHODS This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared. RESULTS Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors. CONCLUSION The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM.
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9
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Preoperative Predictors of Futile Resection of Intraabdominal Extrahepatic Metastases from Hepatocellular Carcinoma. World J Surg 2021; 45:1144-1151. [PMID: 33521877 DOI: 10.1007/s00268-020-05907-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND The management of post-liver resection recurrence is often the life-limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post-resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post-metastasectomy. METHODS We performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution. RESULTS Of the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15-89 months). Twenty-one patients (84%) developed recurrence post-metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post-metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9-23.0)) compared to those who did not (89 months (95% CI 24.8-153.1), p = 0.004). CONCLUSION Patients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post-metastasectomy.
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10
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Invenizzi F, Iavarone M, Donato MF, Mazzucco A, Torre M, Conforti S, Rimessi A, Zavaglia C, Schiavon M, Comacchio G, Rea F, Boetto R, Cillo U, Dondossola D, De Carlis L, Lampertico P, Nosotti M, Mendogni P. Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience. Front Oncol 2020; 10:381. [PMID: 32351877 PMCID: PMC7175841 DOI: 10.3389/fonc.2020.00381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 03/04/2020] [Indexed: 12/11/2022] Open
Abstract
Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9–306) since LT and PMR was performed after 2.4 months (0–43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50–365); median post-operative overall stay 5 days (2–11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7–213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12–74), respectively, with a median OS of 51 months (95%CI 24–78). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.
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Affiliation(s)
- Federica Invenizzi
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Maria Francesca Donato
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Alessandra Mazzucco
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Massimo Torre
- Thoracic Surgery Unit, Ospedale Niguarda, Milan, Italy
| | | | | | - Claudio Zavaglia
- Hepatology and Gastroenterology Department, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Marco Schiavon
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Giovanni Comacchio
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Federico Rea
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Riccardo Boetto
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, Padua, Italy
| | - Daniele Dondossola
- HBP Surgery and Liver Transplantation Unit, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.,University of Milan, Milan, Italy
| | - Mario Nosotti
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Paolo Mendogni
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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11
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Okamura Y, Sugiura T, Ito T, Yamamoto Y, Ashida R, Ohgi K, Uesaka K. The Achievement of a Sustained Virological Response Either Before or After Hepatectomy Improves the Prognosis of Patients with Primary Hepatitis C Virus-Related Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:4566-4575. [PMID: 31602577 DOI: 10.1245/s10434-019-07911-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC). Achieving a sustained virological response (SVR) is associated with a reduced risk of recurrence. The recent introduction of direct acting antivirals (DAAs) has resulted in SVR rates of nearly 100% in treated patients. The purpose of the present study was to clarify the outcomes in patients who underwent antiviral therapy and patients without antiviral therapy. METHODS This retrospective study included 220 patients with primary HCV-related HCC who underwent hepatectomy. An SVR was defined as a serum HCV-RNA titer below the detection sensitivity limit at 6 months after the termination of antiviral therapy. Postoperative antiviral therapy was introduced after confirming that there was no early recurrence. RESULTS Eighty-eight patients received antiviral therapy. Among these, 58 patients (66%) obtained an SVR. With the exception of one patient, all patients who received DAAs obtained an SVR. The overall survival rate of the pre-operative SVR group was significantly better than that of the preoperative untreated group (P = 0.045). Moreover, there was no recurrence at 3 years after surgery in the pre-operative SVR group. The achievement of an SVR was an independent predictor of overall survival [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59-0.94, P = 0.011] and recurrence (HR 0.61, 95% CI 0.40-0.94, P = 0.024). CONCLUSIONS Obtaining an SVR either before or after surgery was associated with the suppression of HCC recurrence after hepatectomy in patients with primary HCV-related HCC.
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Affiliation(s)
- Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto-Nagaizumi, Shizuoka, Japan
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12
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Long-Term Survival and Prognostic Factors of Pulmonary Metastasectomy in Liver Cancer: A Systematic Review and Meta-Analysis. World J Surg 2018; 42:2153-2163. [PMID: 29435629 DOI: 10.1007/s00268-017-4431-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Lung is the most common extrahepatic metastatic organ of liver cancer. Surgical resection is a common local treatment for pulmonary metastasis. But the long-term prognosis of pulmonary metastasectomy varies greatly due to the small sample size and different results of previous studies. Therefore, we conducted this meta-analysis to evaluate the combined 5-year overall survival (OS) rate and prognostic factors after pulmonary metastasectomy in liver cancer. METHODS Key words such as liver cancer pulmonary metastasis and metastasectomy were retrieved firstly in PubMed, Cochrane Library, Embase and Chinese Wanfang databases. Eligible studies were identified by manual searches. Each included study should report 5-year OS rate and/or prognostic factors of pulmonary metastasectomy. Newcastle-Ottawa Scale was used for quality assessment, and heterogeneity was estimated by I2. We calculated the combined 5-year survival rates and determined the prognostic factors for OS by the hazard ratios (HR) and number of events. RESULTS Seventeen cohort studies with a total of 513 patients were included in this meta-analysis. The combined 5-year survival rates after pulmonary metastasectomy were 33% [95% confidence interval (95% CI) 29-37%]. The poor prognostic factors were disease-free interval (DFI) < 12 months (HR = 2.421 95% CI 1.384 4.236) and existence of cirrhosis (HR = 1.936 95% CI 1.031 3.636). CONCLUSION The 5-year OS rate of patients with pulmonary metastasectomy after resection of primary liver cancer is 33%. DFI < 12 months and existence of cirrhosis are probably poor prognostic factors.
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13
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Nagano H, Obi S, Hatano E, Kaneko S, Kanai F, Omata M, Tsuji A, Itamoto T, Yamamoto K, Tanaka M, Kubo S, Hirata K, Nakamura H, Tomimaru Y, Yamanaka T, Kojima S, Monden M. Multicenter, randomized, controlled trial of S-1 monotherapy versus S-1 and interferon-α combination therapy for hepatocellular carcinoma with extrahepatic metastases. Hepatol Res 2018; 48:717-726. [PMID: 29377364 DOI: 10.1111/hepr.13067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 01/20/2018] [Accepted: 01/24/2018] [Indexed: 02/08/2023]
Abstract
AIM No effective therapies for extrahepatic metastases from hepatocellular carcinoma (HCC) have yet been identified. Previous studies suggested a potentially promising antitumor effect of combination therapy of S-1, a novel oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)-α. The present study aimed to investigate the clinical efficacy of single agent S-1 and S-1/IFN-α for HCC patients with extrahepatic metastases in a randomized, open-label, multicenter trial. METHODS A total of 103 patients with HCC with extrahepatic metastases were randomly assigned to the S-1/IFN-α group, receiving the combination of S-1 and IFN-α, or the S-1 group, receiving the single agent of S-1. Clinical efficacy and adverse events were compared between the two groups. RESULTS A total of 49 patients in the S-1/IFN-α group and 51 patients in the S-1 group were included in the efficacy analysis. The response rate was 22.4% (11/49) in the S-1/IFN-α group and 13.7% (7/51) in the S-1 group; there was no significant difference. Overall and progression-free survival in the two groups were also not significantly different (1-year overall survival 50.8% vs. 72.4%, median progression-free survival 127 days vs. 157 days). The incidence of grade ≥3 adverse events in the S-1/IFN-α group was 62.7% (32/51), which tended to be higher than in the S-1 group (43.1% [22/51]). CONCLUSIONS Oncological outcomes in both treatment groups were favorable compared with previous reports, though there was no significant beneficial effect of adding IFN-α to S-1 for the treatment of HCC patients with extrahepatic metastases.
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Affiliation(s)
- Hiroaki Nagano
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.,Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shuntaro Obi
- Department of Gastroenterology and Hepatology, Kyoundo Hospital of the Sasaki Institute, Tokyo, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Fumihiko Kanai
- Department of Gastroenterology, University of Tokyo, Tokyo, Japan
| | - Masao Omata
- Department of Gastroenterology, University of Tokyo, Tokyo, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Kochi Health Science Center, Kochi, Japan
| | - Toshiyuki Itamoto
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuhide Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masatoshi Tanaka
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koichi Hirata
- Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan
| | - Hideji Nakamura
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yoshito Tomimaru
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Takeharu Yamanaka
- Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan
| | - Shinsuke Kojima
- Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan
| | - Morito Monden
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
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14
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Noda T, Eguchi H, Iwagami Y, Yamada D, Asaoka T, Gotoh K, Kawamoto K, Kobayashi S, Hashimoto Y, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M. Minimally invasive liver resection for hepatocellular carcinoma of patients with liver damage B: A propensity score-based analysis. Hepatol Res 2018; 48:539-548. [PMID: 29316082 DOI: 10.1111/hepr.13057] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 01/05/2018] [Accepted: 01/06/2018] [Indexed: 12/16/2022]
Abstract
AIM Minimally invasive liver resection (MILR) is considered a safe and feasible treatment for malignant liver tumors. However, few studies have investigated the surgical outcomes of MILR in patients with impaired liver function. Liver damage is used for consideration of hepatectomy. The aim of this study is to clarify the efficacy of MILR for patients with impaired liver function by using propensity score matching. METHODS Ninety-nine patients with liver damage B underwent hepatic resection were analyzed. The patients were divided into two groups, the MILR group (n = 24) and the open liver resection (OLR) group (n = 75). After matching of a propensity score, we compared clinicopathological features and surgical outcomes. RESULTS After matching, 36 patients (18 patients from each group) were selected and the patients' characteristics and tumor characteristics were not significantly different between the two groups. Blood loss (P = 0.0163) and complication rate (P = 0.0162) were significantly decreased in the MILR group. Complications were observed in eight patients, comprising one patient in the MILR group and seven patients in the OLR group. The postoperative hospital stay was significantly shortened in the MILR group (P = 0.0118). CONCLUSION Minimally invasive liver resection might be effective for patients with impaired liver function. It reduces surgical complications and consequently shortens hospitalization time.
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Affiliation(s)
- Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Koichi Kawamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yasuji Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.,Department of Surgery, Yao Municipal Hospital, Osaka, Japan
| | - Yutaka Takeda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.,Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.,Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Koji Umeshita
- Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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15
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Zhang X, Li C, Wen T, Peng W, Yan L, Yang J. Outcomes of Salvage Liver Transplantation and Re-resection/Radiofrequency Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma: A New Surgical Strategy Based on Recurrence Pattern. Dig Dis Sci 2018; 63:502-514. [PMID: 29238896 DOI: 10.1007/s10620-017-4861-y] [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: 09/04/2017] [Accepted: 11/19/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND The treatment of intrahepatic recurrent hepatocellular carcinoma (HCC) has been poorly investigated, and the optimal treatment strategy remains unclear. AIMS The aim of this study was to compare outcomes between salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) for intrahepatic recurrent HCC according to recurrence pattern. METHODS Based on postoperative histopathological examination, 122 patients with intrahepatic recurrent HCC were divided into an intrahepatic metastasis (IM, n = 75) group and a multicentric occurrence (MO, n = 47) group. The demographic, clinical, and primary and recurrent tumor characteristics of the IM group and the MO group were collected and compared. Overall survival (OS) and disease-free survival (DFS) were analyzed, and subgroup analysis according to retreatment type (SLT vs. RR/RFA) was conducted. Twenty-nine clinicopathological variables potentially related to prognostic factors affecting survival were analyzed using a Cox proportional hazard model. RESULTS The patients that received SLT treatment exhibited favorable DFS compared to patients that received RR/RFA (P = 0.002). OS (P < 0.001) and DFS (P = 0.008) rates were significantly increased in the MO group compared with in the IM group. Subgroup analysis revealed that DFS was significantly improved for patients in the MO group treated with SLT compared to patients treated with RR/RFA (P = 0.017). Recurrence pattern was an independent prognostic factor for both OS [hazard ratio (HR) = 0.093, 95% confidence interval (CI): 0.026-0.337, P < 0.001] and DFS (HR = 0.318, 95% CI: 0.125-0.810, P = 0.016; HR = 3.334, 95% CI: 1.546-7.18, P = 0.002). CONCLUSIONS For patients with intrahepatic recurrent HCC, an MO recurrence pattern is associated with better long-term outcomes than the IM pattern. SLT is the preferred option for intrahepatic recurrent HCC, especially for MO cases.
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Affiliation(s)
- Xiaoyun Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China.
| | - Wei Peng
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Lunan Yan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China
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16
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Takahashi Y, Ikeda N, Nakajima J, Sawabata N, Chida M, Horio H, Okumura S, Kawamura M. Prognostic Analysis of Surgical Resection for Pulmonary Metastasis from Hepatocellular Carcinoma. World J Surg 2017; 40:2178-85. [PMID: 27255943 DOI: 10.1007/s00268-016-3580-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Pulmonary metastases are the most common among extrahepatic recurrences from hepatocellular carcinoma (HCC). It causes high risk of HCC-related death, despite recent progress in therapeutic options. However, a role of pulmonary metastasectomy as well as prognostic factors after metastasectomy has not been well established. We aimed to investigate survival outcomes and prognostic factors after pulmonary resection for metastases from HCC. METHODS A series of 93 patients who underwent pulmonary resections for metastases from HCC between June 1990 and July 2013 from multi-institutional database were retrospectively evaluated. Perioperative clinicopathological data and their association with prognosis were investigated. RESULTS Of 93 patients, 77 had one pulmonary metastasis, and 16 had two or more. Recurrence after pulmonary resection was noted in 60 patients (64.5 %). The estimated 5-year overall survival rate was 41.4 % with median survival time after pulmonary metastatectomy of 39.0 months. Univariate prognostic analysis showed that disease-free interval of ≥12 months was significantly associated with favorable outcomes in both overall survival (5-year rate, 59.3 vs. 28.7 %, p = 0.026) and disease-specific survival (5-year rate, 62.5 vs. 36.2 %; p = 0.038) after pulmonary metastatectomy. A multivariate analysis revealed that disease-free interval was an independent prognostic factor (HR = 2.020, 95 % CI, 1.069-3.816, p = 0.030). CONCLUSION We have shown that a disease-free interval was an independent prognostic factor in patients who underwent pulmonary resection for metastasis from HCC. Also, pulmonary metastasectomy can be one of the therapeutic choices for select patients.
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Affiliation(s)
- Yusuke Takahashi
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
| | - Norihiko Ikeda
- Department of Surgery, Tokyo Medical University, Tokyo, Japan
| | - Jun Nakajima
- Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | | | - Masayuki Chida
- Department of General Thoracic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Hirotoshi Horio
- Department of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Sakae Okumura
- Department of Chest Surgery, Cancer Institute Hospital, Tokyo, Japan
| | - Masafunmi Kawamura
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
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17
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Preoperative maximal removal rate of technetium-99m-galactosyl-human serum albumin of the remnant liver is associated with postoperative tumor relapse in hepatitis C virus-related hepatocellular carcinoma. Nucl Med Commun 2017; 39:28-34. [PMID: 29099413 DOI: 10.1097/mnm.0000000000000773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Prognosis in patients with hepatocellular carcinoma (HCC) is not only influenced by tumor-related factors but also by the background liver functions. The maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) of the remnant liver (rGSA-Rmax) is a useful candidate for predicting the liver function and clarifying the relationship between the remnant liver functional reserve and tumor-free survival in patients who have undergone hepatectomy. PATIENTS AND METHODS One hundred and sixty-five patients with HCC who underwent curative hepatectomy were divided into three groups of hepatitis B virus (B-HCC; n=42), hepatitis C virus (C-HCC, n=58), and non-B, non-C (NBNC-HCC, n=65). The relationship between rGSA-Rmax and survival was examined by univariate and multivariate analyses. RESULTS In the C-HCC group, the albumin, or LHL15, level was significantly lower, and alanine aminotransferase, ICGR15, and the prevalence of grade B liver damage were significantly higher than other two groups (P<0.05). GSA-Rmax or rGSA-Rmax was not different between the three groups. Lower GSA-Rmax and rGSA-Rmax were only significantly associated with lower tumor-free survival in the C-HCC group by the univariate analysis (P<0.05) but not significantly by the multivariate analysis. CONCLUSION GSA-Rmax and rGSA-Rmax reflect the severity of liver dysfunction and furthermore, the lower rGSA-Rmax is useful as a complementary factor to predict the early HCC recurrence after hepatectomy.
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18
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Yang SL, Luo YY, Chen M, Zhou YP, Lu FR, Deng DF, Wu YR. A systematic review and meta-analysis comparing the prognosis of multicentric occurrence and vs. intrahepatic metastasis in patients with recurrent hepatocellular carcinoma after hepatectomy. HPB (Oxford) 2017; 19:835-842. [PMID: 28734693 DOI: 10.1016/j.hpb.2017.06.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 06/02/2017] [Accepted: 06/07/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this meta-analysis was to evaluate the prognosis of patients with different types of hepatocellular cancer (HCC) recurrence following hepatectomy. Specifically, it evaluated overall survival and disease-free survival in HCC patients with multicentric occurrence (MO) or intrahepatic metastasis (IM). METHODS Medline, Cochrane, EMBASE, and Google Scholar were searched until August 22, 2016 using the following search terms: hepatocellular carcinoma, multicentric occurrence, intrahepatic metastasis, early recurrence, and late recurrence. Prospective, retrospective, and case control studies were included. RESULTS The pooled results showed that patients in the MO group had lower risk of death than the IM group (pooled HR = 0.495, 95% CI = 0.378 to 0.648, P < 0.001). The MO group also had significantly longer disease-free survival than the IM group (pooled HR = 0.774, 95% CI = 0.663 to 0.903, P = 0.001). Sensitivity analysis indicated that no one study dominated the findings and that the data are robust. Overall the included studies were of good quality. CONCLUSION This study found that MO patients have greater survival following surgery than IM patients, indicating the prognosis of MO patients is significantly better than that for IM patients.
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Affiliation(s)
- Sheng-Lan Yang
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
| | - Ying-Ying Luo
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
| | - Min Chen
- Department of Geriatric, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, PR China.
| | - Yan-Ping Zhou
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
| | - Fu-Rong Lu
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
| | - Dan-Fang Deng
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
| | - Yan-Ran Wu
- Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China
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19
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Surgical Resection of Metachronous Lymph Node Metastasis From Hepatocellular Carcinoma: Three Case Reports and Review of the Literature. Int Surg 2017. [DOI: 10.9738/intsurg-d-15-00114.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The prognosis for hepatocellular carcinoma (HCC) patients with lymph node (LN) metastasis is generally poor, and no consensus has yet been reached on the optimum treatment strategy. We observed 3 cases involving patients with HCC and associated metachronous LN metastasis, who benefited from surgical resection of the metastatic LNs. Each of the 3 patients had solitary LN metastasis for which selective LN resection was performed, and all had C-type cirrhosis as a background disease. There were no other uncontrolled lesions at the time of LN resection. However, additional treatments were required in cases 1 and 3 to control intrahepatic lesions that recurred following the lymphadenectomy. The overall survival in cases 1 and 3 has been >5 years, with case 1 still under observation. Case 2 also remains under follow-up at 6 months after surgery. Surgical resection could be a beneficial strategy for treatment of metachronous LN metastasis arising from HCC in some cases, particularly those involving a solitary LN metastasis with no other uncontrolled lesions.
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20
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Distinct Recurrence Risk Factors for Intrahepatic Metastasis and Multicenter Occurrence After Surgery in Patients with Hepatocellular Carcinoma. J Gastrointest Surg 2017; 21:312-320. [PMID: 27815759 DOI: 10.1007/s11605-016-3311-z] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 10/13/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND OBJECTIVES Intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) includes intrahepatic metastasis (IM) and multicenter occurrence (MO). The risk factors for these two types of intrahepatic recurrence have not been well defined. METHODS The type of intrahepatic recurrence was determined based on histopathological features of 93 HCC patients who underwent a repeat hepatectomy for recurrent HCC. Various clinical and pathological factors were analyzed to define distinct risk factors for different types of intrahepatic recurrence. RESULTS The recurrence rates at 1, 2, 3, 5, and 8 years postoperatively were 22.4, 42.9, 61.2, 85.7, and 100 %, respectively, in patients with IM and 5.0, 25.0, 45.5, 67.5, and 100 %, respectively, in patients with MO (p = 0.005). A total of 16 clinical and pathological factors were tested in univariable and multivariable analyses. We found that large-size tumor (>5 cm), multiple tumors (two or more), and vascular invasion were significantly associated with IM recurrence, and liver cirrhosis and Ishak hepatic inflammatory activity were highly associated with MO recurrence. In addition, blood transfusion and a high hepatitis B virus (HBV)-DNA load (>2000 IU/ml) were independent risk factors common to both IM and MO recurrences. CONCLUSIONS IM and MO recurrences were associated with distinct risk factors, while blood transfusion and high HBV-DNA load (>2000 IU/ml) were independent risk factors common to both IM and MO recurrences.
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21
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Gavriilidis P, Askari A, Azoulay D. Survival following redo hepatectomy vs radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2017; 19:3-9. [PMID: 28341429 DOI: 10.1016/j.hpb.2016.10.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 09/24/2016] [Accepted: 10/02/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Redo hepatic resection (RHR) and radiofrequency ablation (RFA) are salvage treatment choices for recurrent hepatocellular carcinoma (RHCC). As yet, it is unclear as to which treatment modality is superior in terms of long term survival. The aim of this study was to compare the survival benefits and treatment efficacy of RHR and RFA for recurrent HCC. METHODS A literature review using the EMBASE, Medline, Google scholar, and Cochrane databases was performed. Meta-analyses were performed using an inference of variance, random effects model for 1, 3 and 5-year Disease Free Survival (DFS) and Overall Survival (OS). Secondary outcomes were major morbidity and mortality. RESULTS Five retrospective studies including 639 patients were eligible. Overall, there were no differences in 1, 3 and 5-year DFS or OS for patients undergoing RHR or RFA for recurrent HCC. Comparison between the two groups demonstrated similar 5-year DFS (HR 0.86, 95% CI 0.67-1.11, p = 0.250) and 5-year OS (HR 1.03, 95% CI 0.83-1.27, p = 0.082). However, RFA had a lower morbidity rate (2%) compared with RHR (17%, p < 0.001). CONCLUSION This study demonstrates, neither RHR nor RFA appeared to be superior in terms of DFS and OS. Well-constructed, randomised, multicenter trials will be required to determine if a true difference exists.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of HPB Surgery and Liver Transplantation, Henri Mondor University Hospital, Créteil, France; Department of HPB and Transplant Surgery, St James's University Hospital, Beckett Str, Leeds LS9 7TF, UK
| | | | - Daniel Azoulay
- Department of HPB Surgery and Liver Transplantation, Henri Mondor University Hospital, Créteil, France; INSERM U 955, Créteil, France.
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22
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Dai WC, Cheung TT. Strategic overview on the best treatment option for intrahepaitc hepatocellular carcinoma recurrence. Expert Rev Anticancer Ther 2016; 16:1063-72. [PMID: 27548586 DOI: 10.1080/14737140.2016.1226136] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The long-term survival after hepatectomy for HCC remains unsatisfactory because of the high incidence of recurrence. The cumulative 5-year recurrence rate ranged from 60-100% in previous studies and majority of them remains intrahepatic recurrence. The therapeutic modalities commonly used for primary tumors, including surgical resection, liver transplantation, TACE, local ablative therapy and radiotherapy have been used to treat recurrent tumors in the liver remnant and the outcomes with the heterogeneous therapeutic options are reviewed. It is important to note that the level of evidence for most therapeutic options is limited to cohort investigations with few RCTs and most were limited due to enrollment of various tumor stages and did not compare treatment modalities for specific tumor stages. AREAS COVERED A literature search for recurrent HCC was performed using Medline and PubMed up to May 2016. Expert commentary: The long term survival results after re-resection for recurrent HCC were favourable and aggressive management of postoperative intrahepatic recurrence remains the most important strategy in prolonging the survival of patients after resection of HCC.
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Affiliation(s)
- Wing Chiu Dai
- a Department of Surgery , The University of Hong Kong , Hong Kong , China
| | - Tan To Cheung
- a Department of Surgery , The University of Hong Kong , Hong Kong , China
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Mise Y, Hasegawa K, Shindoh J, Ishizawa T, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, Kokudo N. The Feasibility of Third or More Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma. Ann Surg 2015; 262:347-357. [PMID: 25185473 DOI: 10.1097/sla.0000000000000882] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES To investigate the feasibility and prognostic benefits of third or more hepatectomy (third or more Hx) for recurrent hepatocellular carcinoma. BACKGROUND Second hepatectomy (second Hx) has been accepted as an effective treatment of recurrent hepatocellular carcinoma after first hepatectomy (first Hx). However, the feasibility and efficacy of third or more Hx have not been adequately assessed. METHODS Data were reviewed from 1340 patients with hepatocellular carcinoma who underwent curative hepatectomy. Among them, 941, 289, and 110 underwent first Hx, second Hx, and third or more Hx, respectively. Surgical outcomes and long-term survival were compared among the groups. RESULTS Surgical duration was significantly longer in third or more Hx (median, 6.4 hours) than in second Hx (median, 5.9 hours). Postoperative bile leakage and wound infection were more frequently observed in third or more Hx versus second Hx (12.5% vs 6.2%, [P = 0.04] and 2.9% vs 0.4% [P = 0.03], respectively). Three and 5-year disease-free survival rates were 36.8% and 27.1% in first Hx, 24.4% and 17.9 % in second Hx, and 26.1% and 12.8% in third or more Hx, respectively (P < 0.01 [first Hx vs third Hx], P = 0.95 [second Hx vs third or more Hx]). The 5-year overall survival rates from each resection were similar among the groups (65.3%, 60.5%, 68.2%, respectively). The 5- and 10-year overall survival rates from initial hepatectomy in patients who received third or more Hx were 91.4% and 75.5%, respectively. CONCLUSIONS Third or more Hx is technically demanding in terms of surgical duration and morbidity compared with second Hx. However, aggressive repeat resection offers a survival similar to second Hx, leading to cumulative long-term survival from initial resection.
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Affiliation(s)
- Yoshihiro Mise
- *Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan †Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
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Huang J, Yan L, Wu H, Yang J, Liao M, Zeng Y. Is radiofrequency ablation applicable for recurrent hepatocellular carcinoma after liver transplantation? J Surg Res 2015; 200:122-30. [PMID: 26277218 DOI: 10.1016/j.jss.2015.07.033] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Revised: 06/28/2015] [Accepted: 07/21/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND Radiofrequency ablation (RFA) is a radical treatment for both primary and recurrent small hepatocellular carcinoma (HCC) with an optimistic outcome which is comparable with surgery. For localized recurrence of HCC after liver transplantation (LTx), surgical resection is considered the most favorable treatment. When surgical resection is contraindicated or technically infeasible, whether RFA is as efficient after transplantation as in nontransplant settings remains unclear. MATERIALS AND METHODS A cohort study was undertaken in a population of patients that had a recurrence of HCC after LTx to evaluate the outcomes of different modalities (surgery, RFA, and conservative therapy) on long-term survival. RESULTS Seventy-eight of the 486 HCC patients who received LTx had a recurrence (16%). Fifteen patients underwent surgical resection, and 11 patients were treated with RFA. The remaining 52 patients received conservative therapy (17 patients with sirolimus plus sorafenib regimen; the others were treated with conventional supportive therapy). The 1-, 3-, and 5-y overall survival rates were 92%, 51%, and 35% for the patients treated with surgery and 87%, 51%, and 28% for the patients that received RFA. The corresponding 1-, 3-, and 5-y rerecurrence-free survival rates were 83%, 16%, and 16% for the patients treated with surgery and 76%, 22%, and 0% for the patients that received RFA, respectively. There was no significant difference in overall survival or rerecurrence-free survival between the surgical resection group and the RFA group (P = 0.879, P = 0.745). CONCLUSIONS For HCC recurrence after LTx, RFA is preferable when surgical resection is contraindicated or technically infeasible and provides comparable long-term survival compared with surgery.
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Affiliation(s)
- Jiwei Huang
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Lunan Yan
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Wu
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jiayin Yang
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Mingheng Liao
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Division of Liver Transplantation, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
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Chevallier P, Baudin G, Anty R, Guibal A, Chassang M, Avril L, Tran A. Treatment of hepatocellular carcinomas by thermal ablation and hepatic transarterial chemoembolization. Diagn Interv Imaging 2015; 96:637-46. [DOI: 10.1016/j.diii.2015.04.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 04/13/2015] [Indexed: 12/15/2022]
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Clinical significance of surgical resection of metastatic lymph nodes from hepatocellular carcinoma. Surg Today 2014; 45:1112-20. [PMID: 25205550 DOI: 10.1007/s00595-014-1028-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 08/20/2014] [Indexed: 01/24/2023]
Abstract
PURPOSE The clinical significance of the surgical resection of metastatic lymph nodes (LN) from patients with hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to evaluate the significance of the surgical resection of LN metastasis of HCC. METHODS Among 961 patients who underwent surgical resection for HCC in our hospital, LN metastasis was identified in 38 patients. In these patients, the metastatic LN were removed completely in 22 patients (complete removal group), and incompletely or not removed in 16 patients (control group). The long-term prognosis after LN metastasis was compared between the two groups. RESULTS The overall survival rate after LN metastasis was significantly better in the complete removal group (1-, 3- and 5-year: 71.2, 58.0 and 49.7%, respectively) than in the control group (45.9, 23.0 and 15.3%, respectively, p = 0.0477). LN metastasis was not the cause of death in any of the patients in the complete removal group, whereas it was a cause in some patients in the control group. No local LN recurrence was identified in the complete removal group. CONCLUSIONS The present results suggest that the complete removal of metastatic LN from HCC is clinically beneficial in selected patients.
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RETRACTED ARTICLE: Clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy. Med Oncol 2014; 31:175. [DOI: 10.1007/s12032-014-0175-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 08/09/2014] [Indexed: 12/12/2022]
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Saraswat VA, Pandey G, Shetty S. Treatment algorithms for managing hepatocellular carcinoma. J Clin Exp Hepatol 2014; 4:S80-9. [PMID: 25755616 PMCID: PMC4284287 DOI: 10.1016/j.jceh.2014.05.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Accepted: 05/08/2014] [Indexed: 12/12/2022] Open
Abstract
Early diagnosis and aggressive therapy improves outcome in hepatocellular carcinoma (HCC). Several potentially curative as well as palliative treatment options are available for patients. The choice of therapy is influenced by factors such as extent of tumor and severity of underlying liver dysfunction as well as availability of resources and of expertise. A systematic, algorithmic approach would ensure optimal therapy for each patient and is likely to improve outcomes. Even after receiving therapy for HCC, patients remain at risk for recurrent HCC as well as progression of underlying cirrhosis. Proper assessment and monitoring is needed for the underlying liver disease, which may progress to liver failure and have a major impact on long-term survival. Comprehensive care for patients with cirrhosis includes interventions such as antiviral therapy for HBV and HCV, abstention from alcohol, management of fatty liver disease, endoscopic surveillance and treatment for complications of portal hypertension and, if indicated, immunization against HAV and HBV. An algorithmic approach is useful for choosing the most appropriate treatment option for the individual patient from among the various options that are available. The general consensus is that the BCLC system should be preferred for staging HCC as it is useful in predicting outcomes and planning treatment. The BCLC system classifies patients with HCC into five categories: very early, early, intermediate, advanced, and terminal. It incorporates data on tumor status (number and size of nodules, vascular invasion, extra-hepatic spread), liver function (CTP status, presence of portal hypertension) and overall health status (constitutional symptoms, cancer symptoms, performance status). Treatment allocation according to sub-class of patients is a merit of the BCLC system; a few limitations have been noted, particularly with respect to patients with BCLC stage B and C disease. The treatment algorithm as per BCLC system is summarized in this review.
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Key Words
- AJCC–UICC, American Joint Committee on Cancer and Union for International Cancer Control
- ALT, alanine aminotransferase
- BCLC
- BCLC, Barcelona Clinic Liver Cancer
- CEUS, contrast-enhanced ultrasound
- CLIP, Cancer of the Liver Italian Program
- CTP, Child–Turcotte–Pugh criteria
- CUPI, Chinese University Prognostic Index
- EASL, European expert panel
- EBRT, external beam radiotherapy
- HCC, hepatocellular carcinoma
- JIS, Japanese integrated system
- LT, liver transplantation
- MAA, macro-aggregate albumin
- MCT, microwave coagulation therapy
- MWA, microwave ablation
- NCCN, National Comprehensive Cancer Network
- PAI, percutaneous acetic acid injection
- PEI, percutaneous ethanol injection
- PLT, primary LT
- RBV, ribavirin
- RECIST, response evaluation criteria in solid tumors
- RFA, radiofrequency ablation
- SIRT, Selective Internal Radiation Treatment
- SLT, salvage liver transplant
- TACE, trans-catheter arterial chemo-embolization
- TACE-DEB, TACE with drug eluting beads
- TAE, transarterial embolization
- TAI, trans-catheter hepatic arterial infusion
- TARE, transarterial radio-embolization
- TNM, Tumor-Node-Metastasis
- WHO, World Health Organization
- bm-JIS, biomarker JIS
- liver cancer
- staging
- treatment algorithm
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Affiliation(s)
- Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Lu WP, Dong JH. Hepatectomy for hepatocellular carcinoma in the era of liver transplantation. World J Gastroenterol 2014; 20:9237-9244. [PMID: 25071316 PMCID: PMC4110553 DOI: 10.3748/wjg.v20.i28.9237] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 03/05/2014] [Accepted: 06/13/2014] [Indexed: 02/07/2023] Open
Abstract
The aim of management of hepatocellular carcinoma (HCC) is to improve the prognosis of the patients by radical resection and preserve remnant liver function. Although liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications. Therefore, hepatectomy could be the first choice of treatment in selected patients with HCC. However, the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis. New strategies are required to improve the long-term outcome of HCC after hepatectomy. In this paper, we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence. Some aggressive treatments for tumor recurrence to extend long-term survival are also involved. We believe that hepatectomy combined with other therapies, such as portal vein embolization, transarterial chemoembolization, radioembolization, antiviral treatment, radiofrequency ablation and salvage transplantation, is a promising treatment modality for HCC and may improve survival greatly.
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Takemura N, Hasegawa K, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, Kokudo N. Surgical resection of peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma. Br J Surg 2014; 101:1017-1022. [PMID: 24828028 DOI: 10.1002/bjs.9489] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND Peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma (HCC) occur occasionally after biopsy, percutaneous therapy or resection, and spontaneously, with no effective treatment available. The objective of this study was to clarify the indications for, and benefits of, surgical resection of such HCC implants. METHODS This was a retrospective analysis of patients who underwent resection for peritoneal or chest wall implants from HCC over 14 years (1997-2011). Indications for surgery for implanted HCC were: limited number of implanted lesions including those found incidentally during surgery; intrahepatic lesion absent or predicted to be locally controllable; and absence of ascites with sufficient hepatic functional reserve. Prognostic factors affecting survival after resection were determined by univariable and multivariable analysis. RESULTS A total of 32 patients underwent 36 resections. Cumulative 1-, 3- and 5-year overall survival rates were 71, 44 and 39 per cent respectively, with a median survival time of 34.5 months. Univariable and multivariable analysis revealed that poor perioperative intrahepatic disease control was associated with poor survival. CONCLUSION Surgical resection of implanted HCC may improve long-term survival in selected patients as long as intrahepatic disease is absent or well controlled.
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Affiliation(s)
- N Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Nomoto S, Hishida M, Inokawa Y, Takano N, Kanda M, Nishikawa Y, Fujii T, Koike M, Sugimoto H, Kodera Y. Expression analysis of THOP1 in background liver, a prognostic predictive factor in hepatocellular carcinoma, extracted by multiarray analysis. Ann Surg Oncol 2014; 21 Suppl 3:S443-50. [PMID: 24604581 DOI: 10.1245/s10434-014-3581-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) often recurs and multicentric occurrence is more common than intrahepatic metastases after surgery. Prognostic prediction is insufficient when considering only factors in resected primary tumor. METHODS Control samples, termed supernormal (SN) liver, were taken from 11 cases of metastatic secondary malignancies of the liver. We selected adjacent nonneoplastic liver tissue from a patient with HCC and liver cirrhosis by hepatitis C (CN) for comparison. Expression profiling and methylation arrays were performed. We identified genes showing differences in both arrays. Prognosis was predicted for 179 cases of HCC based on gene expression. RESULTS Expression profiling showed that expression of thimet oligopeptidase (THOP1) gene was decreased 4.119-fold in CN. Methylation array showed a higher value for CN (0.869) than SN (0.488). We studied THOP1 gene expression by real-time reverse transcriptase polymerase chain reaction. The average expression level of THOP1 (THOP1 value × 10(3)/GAPDH) decreased in matching normal tissue (14.53 ± 10.14) relative to SN (78.14 ± 44.50). The group with higher than average THOP1 expression (n = 74) showed significant correlations with prolonged survival (P = 0.0383). Strongly reduced THOP1 expression (<3.0, n = 50) was shown to be an independent prognostic factor by multivariate analysis (P = 0.0024). CONCLUSIONS Expression of the THOP1 gene in the background liver of HCC is likely to be a good biomarker for risk of HCC development. When assessing HCC, it is important to extract prognostic factors from background liver tissue as well as considering malignant factors of the primary cancer lesion.
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Affiliation(s)
- Shuji Nomoto
- Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan,
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Zhuang PY, Shen J, Zhu XD, Zhang JB, Tang ZY, Qin LX, Sun HC. Direct transformation of lung microenvironment by interferon-α treatment counteracts growth of lung metastasis of hepatocellular carcinoma. PLoS One 2013; 8:e58913. [PMID: 23527047 PMCID: PMC3601095 DOI: 10.1371/journal.pone.0058913] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 02/08/2013] [Indexed: 12/27/2022] Open
Abstract
Background Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear. Methods The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry. Results IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor. Conclusion IFN-α inhibited lung metastasis by directly modulating the lung microenvironment.
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Affiliation(s)
- Peng-Yuan Zhuang
- Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Jun Shen
- Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Xiao-Dong Zhu
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Ju-Bo Zhang
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Zhao-You Tang
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Lun-Xiu Qin
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Hui-Chuan Sun
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- * E-mail:
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NAGANO HIROAKI, KOBAYASHI SHOGO, MARUBASHI SHIGERU, WADA HIROSHI, EGUCHI HIDETOSHI, TANEMURA MASAHIRO, TOMIMARU YOSHITO, UMESHITA KOJI, DOKI YUICHIRO, MORI MASAKI. Combined IFN-α and 5-FU treatment as a postoperative adjuvant following surgery for hepatocellular carcinoma with portal venous tumor thrombus. Exp Ther Med 2013; 5:3-10. [PMID: 23251233 PMCID: PMC3524132 DOI: 10.3892/etm.2012.736] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Accepted: 11/30/2011] [Indexed: 12/13/2022] Open
Abstract
The efficacy of combination therapy with subcutaneous interferon (IFN)-α and intra-arterial 5-fluorouracil (5-FU) as a postoperative adjuvant for resectable advanced hepatocellular carcinoma (HCC) invading the major branches of the portal vein (PVTT) was examined. The prognosis of HCC with PVTT (Vp3 or 4) is extremely poor. Recently, we reported the possibility of combination therapy with IFN-α and intra-arterial 5-FU for intractable HCC with PVTT as a postoperative adjuvant and this is the second report. Patients with HCC with PVTT were included (n=50). Thirty consecutive patients with HCC and PVTT were treated with 3 cycles of a combination therapy consisting of arterial 5-FU infusion (300 mg/mm(3)/day, 5 days/week, for the initial 2 weeks) and IFN subcutaneous injection (5 MIU, 3 times/week, 4 weeks) as a postoperative adjuvant following hepatic resection; another 20 patients receiving no IFN/5-FU chemotherapy acted as controls. Results for the IFN/5-FU adjuvant treatment group were as follows: disease-free survival (n=9, 15-109 months), survival with recurrence (n=6, 30-92 months), cancer death (n=9, 14-60 months), death from other causes but no recurrence (n=5, 13-87 months) and death from other causes with recurrence (n=1, 22 months). The 1-year survival rate was 100% in patients treated with IFN/5-FU, and 30% in those without IFN/5-FU as historical controls (n=20). There was a significant difference in disease-free and overall survival rates between the two groups (P<0.0001). In conclusion, IFN/5-FU combination therapy may be a very promising postoperative adjuvant treatment for HCC with PVTT.
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Affiliation(s)
| | | | | | | | | | | | | | - KOJI UMESHITA
- Health Science, Graduate School of Medicine, Osaka University, Osaka,
Japan
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Yokoigawa N, Ogura T, Kwon AH. Successful surgical control of peritoneal dissemination of hepatocellular carcinoma. Case Rep Gastroenterol 2012; 6:612-7. [PMID: 23139651 PMCID: PMC3493013 DOI: 10.1159/000343248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Treatment for the peritoneal dissemination of hepatocellular carcinoma (HCC) has not yet been established. We report a patient with HCC associated with disseminated intra-abdominal tumor. A 74-year-old man was admitted to our hospital. Computed tomography showed a 3 × 3 cm mass in the left hepatic lobe and a giant mass between the stomach and spleen. At laparotomy, the tumor was seen in the medial segment and evaginated to the diaphragm. There was a tumor between the stomach and spleen, confirmed as a 5 × 5 cm tumor evaginated from the left diaphragm, and a 7 × 7 cm tumor adhesive to the spleen. These two tumors were not continuous and were separated. Furthermore, we confirmed a 10 × 10 cm tumor in the pelvic cavity. We performed partial hepatectomy, resection of the tumor evaginated from the diaphragm, resection of the tumor of the spleen and tail of pancreas, and resection of the tumor in the pelvic cavity. Histopathologically, all resected tumors were confirmed to be well-differentiated HCC. HCC rarely disseminates intraperitoneally. It is considered that the peritoneal dissemination of HCC occurred from poorly differentiated or undifferentiated type. Then this report is a rare case. Although surgical treatment of peritoneal dissemination of HCC is not curative, surgery may improve survival and provide good quality of life in selected cases.
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Affiliation(s)
- Norio Yokoigawa
- Department of Surgery, Kansai Medical University, Moriguchi, Japan
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KANNO KIMINORI, KANNO SHOJI, NITTA HIROYUKI, UESUGI NORIYUKI, SUGAI TAMOSTU, MASUDA TOMOYUKI, WAKABAYASHI GO, MAESAWA CHIHAYA. Overexpression of histone deacetylase 6 contributes to accelerated migration and invasion activity of hepatocellular carcinoma cells. Oncol Rep 2012; 28:867-73. [DOI: 10.3892/or.2012.1898] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2012] [Accepted: 05/18/2012] [Indexed: 11/06/2022] Open
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Huang ZY, Liang BY, Xiong M, Zhan DQ, Wei S, Wang GP, Chen YF, Chen XP. Long-term outcomes of repeat hepatic resection in patients with recurrent hepatocellular carcinoma and analysis of recurrent types and their prognosis: a single-center experience in China. Ann Surg Oncol 2012; 19:2515-25. [PMID: 22395985 DOI: 10.1245/s10434-012-2269-7] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Recurrent hepatocellular carcinoma (HCC) after curative resection usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO). The long-term outcomes of repeat hepatic resection in patients with different types of recurrence have not been evaluated in a large number of patients. The surgical indications for recurrent HCC remain controversial. The purpose of this study was to investigate long-term outcomes of repeat hepatic resection and clinicopathologic factors associated with different types of recurrent HCC, and to single out principle differentiating factors between IM and MO. METHODS 82 patients who underwent repeat hepatic resection for recurrent HCC were retrospectively studied. The recurrent type was evaluated by histopathologic analysis of primary and recurrent HCC. The recurrence and survival rates as well as clinicopathologic factors associated with different types of recurrence were analyzed. RESULTS 45 patients (54.9%) had confirmed with IM, and 37 patients (45.1%) had with MO. The recurrence rates in the MO patients after initial or repeat resection were significantly lower than those in the IM patients (p < 0.001). The overall survival rates in the MO patients after initial or repeat resection were significantly higher than those in the IM patients (p < 0.001). Recurrence-free time was identified as the most significant differentiating factor between IM and MO. A recurrence-free time of 18 months after initial resection was a significant cutoff time point for differentiating between IM and MO. A recurrence-free time of less than or equal to 18 months and microvascular invasion at repeat resection were independent adverse prognostic factors for overall survival after repeat hepatic resection. CONCLUSIONS Repeat hepatic resection resulted in much higher survival rates in the MO patients than in the IM patients. Repeat hepatic resection could be recommended for those patients in whom the recurrent HCC occurs more than 18 months after initial resection.
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Affiliation(s)
- Zhi-Yong Huang
- Research Laboratory and Hepatic Surgery Center, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Chen CY, Wu K, Lin WH, Lan TY, Wang SY, Sun JS, Weng PW, Yen RF, Yang RS. High false negative rate of Tc-99m MDP whole-body bone scintigraphy in detecting skeletal metastases for patients with hepatoma. J Formos Med Assoc 2012; 111:140-6. [DOI: 10.1016/j.jfma.2011.01.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2010] [Revised: 11/15/2010] [Accepted: 01/03/2011] [Indexed: 01/12/2023] Open
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Peng ZW, Zhang YJ, Liang HH, Lin XJ, Guo RP, Chen MS. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology 2011; 262:689-700. [PMID: 22157201 DOI: 10.1148/radiol.11110637] [Citation(s) in RCA: 156] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To compare prospectively the effects of radiofrequency (RF) ablation after transcatheter arterial chemoembolization (TACE) with those of RF ablation alone in the treatment of recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study was approved by the institutional ethics committee, and all patients gave written informed consent. From January 2002 to December 2006, 139 patients with recurrent HCC measuring 5 cm in diameter or smaller were randomized to receive either sequential TACE and RF ablation (sequential treatment group, n=69) or RF ablation alone (RF ablation group, n=70). The survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Bonferroni correction was applied when multiple comparisons were performed. P<.0083 (.05÷6) was considered indicative of a statistically significant difference. RESULTS The 1-, 3-, and 5-year overall survival rates were 94%, 69%, and 46%, respectively, for the sequential treatment group and 82%, 47%, and 36% for the RF ablation group (P=.037). The corresponding recurrence-free survival rates were 80%, 45%, and 40% for the sequential treatment group and 64%, 18%, and 18% for the ablation group (P=.005). At subgroup analyses, the overall survival for the sequential treatment group was better than that for the RF ablation group for patients with tumor recurrence 1 year or less after initial treatment (P=.004) and those with tumors measuring 3.1-5.0 cm (P=.002) but not for those with tumor recurrence more than 1 year after initial treatment (P=.421) and those with tumors 3.0 cm or smaller (P=.478). The recurrence-free survival in the sequential treatment group was better than that in the RF ablation group for patients with tumors measuring 3.1-5.0 cm (P<.001) but not for those with tumors 3.0 cm or smaller (P=.204). For recurrence-free survival, there was no significant difference between the two groups for patients with tumor recurrence 1 year or less or more than 1 year after initial treatment (P=.020 and P=.111, respectively). Logistic regression analysis showed that treatment allocation and the interval between initial treatment and tumor recurrence were significant prognostic factors for overall survival, whereas the interval between initial treatment and tumor recurrence, treatment allocation, and tumor size were significant prognostic factors for recurrence-free survival. CONCLUSION The efficacy of sequential TACE-RF ablation is better than that of RF ablation alone for recurrent HCC.
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Affiliation(s)
- Zhen-Wei Peng
- Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, and The Second Affiliated Hospital of Guangzhou Medical College, 651 Dongfeng Rd East, Guangzhou 510060, China
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Tiong L, Maddern GJ. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br J Surg 2011; 98:1210-24. [PMID: 21766289 DOI: 10.1002/bjs.7669] [Citation(s) in RCA: 200] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Despite being one of the commonest causes of cancer-related death around the world, only 20 per cent of hepatocellular carcinomas (HCCs) are amenable to curative treatment (surgical resection or liver transplantation). Radiofrequency ablation (RFA) has emerged as a popular therapy for unresectable HCC. There is evidence that the disparity in survival after curative RFA and surgery for HCC, especially tumours smaller than 3 cm in diameter, is narrowing. This review examined the survival and disease recurrence rates after RFA for HCC over the past decade. METHODS A systematic review was conducted using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register and the Database of Abstracts of Reviews of Effects from January 2000 until November 2010. Papers reporting on patients with HCC who were treated with RFA, either in comparison or in combination with other interventions, such as surgery or percutaneous ethanol injection (PEI), were eligible for inclusion. Outcome data collected were overall survival, disease-free survival and disease recurrence rates. Only randomized controlled trials (RCTs), quasi-RCTs and non-randomized comparative studies with more than 12 months' follow-up were included. RESULTS Forty-three articles, including 12 RCTs, were included in the review. The majority of the articles reported the use of RFA for unresectable HCC, often in combination with other treatments such as PEI, transarterial chemoembolization and/or surgery. Overall and disease-free survival rates continue to improve, despite an increase in the size and numbers of tumours treated. More recently some clinicians have used RFA to treat selected patients with resectable HCC, with good outcomes. CONCLUSION RFA provides a valuable treatment option for patients with unresectable HCC. It improves survival in those previously considered to have advanced disease. As progress continues to be made, RFA is gradually being used to treat resectable HCC.
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Affiliation(s)
- L Tiong
- University of Adelaide Department of Surgery, Queen Elizabeth Hospital, Woodville, Adelaide, South Australia 5011, Australia
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Hirokawa F, Hayashi M, Miyamoto Y, Asakuma M, Shimizu T, Komeda K, Inoue Y, Tanigawa N. Appropriate treatment strategy for intrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2011; 15:1182-7. [PMID: 21557020 DOI: 10.1007/s11605-011-1484-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Accepted: 03/08/2011] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The aim of this study is to evaluate the appropriate treatment for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC). METHODS Of 151 patients who underwent initial hepatectomy for HCC, 82 had intrahepatic recurrence and were divided into two groups: group A, ≤2 tumors, each 3 cm in size; and group B, beyond the group A. Survival and treatment in each group were analyzed retrospectively to determine the best therapeutic modality for intrahepatic recurrence. RESULTS The 5-year overall survival and recurrence rate were 65% and 58%, respectively. Overall 1-, 3-, and 5-year survival rates after recurrence were better in group A (100%, 76%, and 54%) than in group B (74%, 23%, and 5.8%; p < 0.001). The clinical backgrounds were not different for each modality. Of the 43 patients in group A, 10 underwent hepatectomy, 21 ablation therapy, and 12 transcatheter arterial chemoembolization (TACE). The survival rate of hepatectomy was similar to that of ablation therapy and significantly better than that of TACE (p = 0.0248). Of the 39 patients in group B, the results of TACE were similar to other therapies after recurrence. CONCLUSIONS Repeat hepatectomy and ablation therapy were more effective than TACE in the group with ≤2 tumors up to 3 cm in size at recurrence, while any treatment modality was more effective than best supportive care, but the outcome was poorer in the group with ≥3 tumors or tumor size ≥3 cm at recurrence.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
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Kakinoki K, Nakamoto Y, Kagaya T, Tsuchiyama T, Sakai Y, Nakahama T, Mukaida N, Kaneko S. Prevention of intrahepatic metastasis of liver cancer by suicide gene therapy and chemokine ligand 2/monocyte chemoattractant protein-1 delivery in mice. J Gene Med 2010; 12:1002-1013. [PMID: 21157824 DOI: 10.1002/jgm.1528] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, largely as a result of intrahepatic metastasis. Using a mouse model of intrahepatic metastasis, we investigated whether chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) could potentiate the antitumor effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system. METHODS Mouse hepatoma cells infected with recombinant adenovirus vectors expressing HSV-tk, CCL2/MCP-1 and LacZ at multiplicities of infection of Ad-tk/Ad-MCP1 = 3/0.03 (T/M(Low)), 3/3 (T/M(High)) and Ad-tk/Ad-LacZ = 3/3 (T/L) were injected into BALB/c mice. RESULTS Intrahepatic tumor growth was significantly lower in T/M(Low) mice. By contrast, no tumor suppression was observed in T/M(High) mice. The tumor-specific cytolytic activities of splenocytes from T/M(Low) and T/M(High) mice were comparable. Immunohistochemical analysis of liver tissues showed similar infiltration by Mac-1(+) and T cells in these animals, whereas the proportions of classical activated (M1) monocytes/macrophages were significantly higher in T/M(Low) mice. In addition, interleukin-12 production was elevated in these tissues. Vascular endothelial growth factor-A expression and CD31(+) microvessels were increased in T/M(High) mice. CONCLUSIONS Collectively, these results demonstrate that an adequate amount of CCL2/MCP-1, together with the HSV-tk/GCV system, may induce T helper 1-polarized antitumor effects without inducing tumor angiogenesis in the microenvironment of intrahepatic HCC progression.
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Affiliation(s)
- Kaheita Kakinoki
- Disease Control and Homeostasis, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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Zhou Y, Sui C, Li B, Yin Z, Tan Y, Yang J, Liu Z. Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review. World J Surg Oncol 2010; 8:55. [PMID: 20591196 PMCID: PMC2904292 DOI: 10.1186/1477-7819-8-55] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2010] [Accepted: 07/01/2010] [Indexed: 02/08/2023] Open
Abstract
Background This study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). Methods Thirty-seven patients who underwent a curative repeat hepatectomy in our hospital were retrospectively studied. An extensive database literature search was performed to obtain for all relevant studies. Results In our series, there were no perioperative deaths during repeat hepatectomy for recurrent HCC. Patients survival after repeat hepatectomy were similar to 429 patients undergoing initial hepatectomy. A computerized search of the Medline and PubMed databases found 29 retrospective studies providing relevant data in 1149 patients were included for appraisal and data extraction. After the repeat hepatectomy, postoperative morbidity ranged from 6.2% to 68.2% with a median per cohort of 23.5 per cent. There were 7 perioperative deaths (0.7 per cent of 993 for whom mortality data were provided). The overall median survival ranged from 21 to 61.5 months, with 1 -, 3 -, and 5-year survival of 69.0% to 100%, 21.0% to 87.0%, and 25.0% to 87.0%, respectively. Conclusions Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC. However, the findings have to be carefully interpreted due to the lower level of evidence. A randomized controlled study is needed to compare repeat hepatectomy and other modalities for recurrent HCC.
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Affiliation(s)
- Yanming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, the First affiliated Hospital of Xiamen University, Xiamen, China
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Lee CY, Bae MK, Park IK, Kim DJ, Lee JG, Choi JS, Han KH, Chung KY. Surgical resection for pulmonary metastasis from hepatocellular carcinoma: analysis of prognosis in relation to primary control. J Surg Oncol 2010; 101:239-43. [PMID: 20127898 DOI: 10.1002/jso.21487] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Advances in local treatments for hepatocellular carcinoma (HCC) have seen better prognosis. There were few studies on surgery for pulmonary metastasis from HCC controlled by local treatment. This study was conducted to analyze prognostic factors after surgery for pulmonary metastasis from HCC. METHODS We reviewed 32 patients who underwent surgery for pulmonary metastasis from HCC and analyzed prognostic factors. RESULTS HCC was controlled by surgery in 16 patients and by local treatment in 16 patients at the time of pulmonary resection. The median survival time after pulmonary resection was significantly better for HCC controlled by surgery, disease-free time >or=12 months, TMN stage I-II, and T factor 1-2 of primary HCC. The median survival time was better for lesion <or=2 and Child-Pugh score A, but they were not significant (P = 0.053, 0.069). In multivariate analysis, HCC controlled by surgical treatment (P = 0.008), and lesion <or=2 (P = 0.030) were independent prognostic factors. CONCLUSION Our Results indicated that surgical resection for pulmonary metastasis from HCC might be beneficial for patients whose HCC was controlled by surgery and the number of lesions was lower than 3.
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Affiliation(s)
- Chang Young Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, South Korea
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Cho HS, Oh JH, Han I, Kim HS. Survival of patients with skeletal metastases from hepatocellular carcinoma after surgical management. ACTA ACUST UNITED AC 2009; 91:1505-12. [PMID: 19880898 DOI: 10.1302/0301-620x.91b11.21864] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Skeletal metastases from hepatocellular carcinoma are highly destructive vascular lesions which severely reduce the quality of life. Pre-existing liver cirrhosis presents unique challenges during the surgical management of such lesions. We carried out a retrospective study of 42 patients who had been managed surgically for skeletal metastases from hepatocellular carcinoma affecting the appendicular skeleton between January 2000 and December 2006. There were 38 men and four women with a mean age of 60.2 years (46 to 77). Surgery for a pathological fracture was undertaken in 30 patients and because of a high risk of fracture in 12. An intralesional surgical margin was achieved in 36 and a wide margin in six. Factors influencing survival were determined by univariate and multivariate analyses. The survival rates at one, two and three years after surgery were 42.2%, 25.8% and 19.8%, respectively. The median survival time was ten months (95% confidence interval 6.29 to 13.71). The number of skeletal metastases and the Child-Pugh grade were identified as independent prognostic factors by Cox regression analysis. The method of management of the hepatocellular carcinoma, its status in the liver, the surgical margin for skeletal metastases, the presence of a pathological fracture and adjuvant radiotherapy were not found to be significantly related to the survival of the patient, which was affected by hepatic function, as represented by the Child-Pugh grade.
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Affiliation(s)
- H S Cho
- Department of Orthopaedic Surgery, Kyungpook National University, College of Medicine, 200 Dongduk-Ro Jung-Gu, Daegu, Korea
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Wang J, Li Q, Sun Y, Zheng H, Cui Y, Li H, Zhou H, Hao X. Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV. Surg Oncol 2009; 18:25-30. [PMID: 18640032 DOI: 10.1016/j.suronc.2008.05.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2008] [Revised: 05/23/2008] [Accepted: 05/31/2008] [Indexed: 12/12/2022]
Abstract
AIMS To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) in China and to identify the differences between them. PATIENTS AND METHODS Histopathologic features of multiple tumors in 82 cases with HCC were analyzed. The two groups, the origin was determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their survival rate, disease-free survival and clinicopathologic differences. RESULTS According to histological findings, 19.5% and 69.5% patients were considered to be MO and IM, respectively. In total 73 cases from the histopathological method were selected and divided into group MO (16 cases) and the group IM (57 cases). Analysis of stepwise regression identified that: Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) were the most important discriminating factors between MO and IM (p<0.05). As for their prognosis, Kaplan-Meier and Log rank test showed the survival rate in group MO was significantly better than that in the group IM (p=0.003). No statistical significance was found between the disease-free survival in group MO and that in group IM (p=0.141). The analysis of Cox's proportional hazards model showed that tumor type (MO or IM) and Child's stage were the important prognostic factors (p=0.002 and 0.014, respectively). CONCLUSIONS The incidence of MO in patients with multiple HCCs related to HBV is only about 20%, which is lower than that of Japan. Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) are the most important discriminating factors between MO and IM. The prognosis of patients with MO compared to IM is significantly better and tumor type (MO or IM) and Child's stage are important prognostic factors.
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Affiliation(s)
- Jian Wang
- Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huanhu Western Road, Hexi District, Tianjin 300060, PR China.
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Therapeutic results of computed-tomography-guided transcatheter arterial chemoembolization for local recurrence of hepatocellular carcinoma after initial transcatheter arterial chemoembolization: the results of 85 recurrent tumors in 35 patients. Dig Dis Sci 2009; 54:661-9. [PMID: 18649138 DOI: 10.1007/s10620-008-0388-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2007] [Accepted: 06/17/2008] [Indexed: 12/15/2022]
Abstract
The aim of this study was to retrospectively evaluate the long-term results of transcatheter arterial chemoembolization (TACE) for the treatment of local recurrence of hepatocellular carcinoma (HCC) after the first TACE. Between September 1992 and October 2004, 85 recurrent HCC nodules of 35 patients were treated by TACE. During the median follow-up period of 15.5 months (range 1.9-58.6 months), 58 of the 85 treated tumors developed local recurrence again after the second TACE. The overall 6-, 12-, and 36-month recurrence-free rates of these tumors after the second TACE were 47.0%, 36.2%, and 25.8%, respectively. Local recurrence of HCC after the first TACE was treated by a second TACE with equivalent efficacy as that of the initial TACE, if segmental chemoembolization was achieved. We regard TACE as the treatment of choice for the management of local recurrence of HCC.
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Kwon JB, Park K, Kim YD, Seo JH, Moon SW, Cho DG, Kim YW, Kim DG, Yoon SK, Lim HW. Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma: Analysis of prognostic factors. World J Gastroenterol 2008; 14:5717-22. [PMID: 18837090 PMCID: PMC2748208 DOI: 10.3748/wjg.14.5717] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors.
METHODS: Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared.
RESULTS: There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ± 28.2 (range: 1-99 mo), and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma (HCC), and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan-Meier analysis revealed that liver transplantation as a treatment for the primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox’s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC.
CONCLUSION: A metastasectomy should be performed before other treatments in selected patients. Although not significant, patients with liver transplantation of a primary HCC survived longer. Liver transplantation might be the most beneficial modality that can offer patients better survival. A multi-institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis.
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Li Q, Wang J, Juzi JT, Sun Y, Zheng H, Cui Y, Li H, Hao X. Clonality analysis for multicentric origin and intrahepatic metastasis in recurrent and primary hepatocellular carcinoma. J Gastrointest Surg 2008; 12:1540-1547. [PMID: 18629593 DOI: 10.1007/s11605-008-0591-y] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2008] [Accepted: 06/16/2008] [Indexed: 01/31/2023]
Abstract
AIMS To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus in China and to identify the differences between them. METHODS Histopathologic and genetic features of primary and recurrent tumors in 160 cases with HCC were analyzed. The two groups, the origin of which was definitely determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their disease-free survival and clinicopathological differences. RESULTS According to histopathological findings, 27.5% and 59.4% patients were considered to be MO and IM, respectively. By comparing the genetic information of loss of heterozygosity and microsatellite instability for 10 different markers between primary and recurrent tumor, 30.0% and 63.8% patients with recurrent HCC were considered to be MO and IM, respectively. In total, 126 cases with unanimous conclusions from the histopathological and genetic method were selected and divided into the MO group (37 cases) and the IM group (89 cases). Analysis of stepwise regression identified that recurrence time, grading, portal vein invasion, tumor number, and Child's stage were the most important discriminating factors between MO and IM (p < 0.05). As for their prognosis, Kaplan-Meier and log rank test showed that the disease-free survival in the MO group was significantly better than in the IM group (p = 0.002). CONCLUSIONS Combined analysis of histopathological and genetic analysis may reflect more exactly the nature of recurrent HCC. The incidence of MO in China is lower than in other countries--30% compared to up to 50% in Japan [Morimoto et al., Journal of Hepatology 39:215-221, 2003; Yamamoto et al., Hepatology 29;1446-1452, 1999]. Recurrence time, tumor grading, portal vein invasion, tumor number, and Child's stage are the most important discriminating factors between MO and IM. The prognosis (disease-free survival) of patients with MO compared to IM is significantly better.
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Affiliation(s)
- Qiang Li
- Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huanhu Western Road, Hexi District, Tianjin, 300060, People's Republic of China.
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Liang HH, Chen MS, Peng ZW, Zhang YJ, Zhang YQ, Li JQ, Lau WY. Percutaneous radiofrequency ablation versus repeat hepatectomy for recurrent hepatocellular carcinoma: a retrospective study. Ann Surg Oncol 2008; 15:3484-93. [PMID: 18679754 DOI: 10.1245/s10434-008-0076-y] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2008] [Revised: 06/19/2008] [Accepted: 06/20/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND Whether percutaneous radiofrequency ablation (PRFA) is as effective as repeat hepatectomy for recurrent small hepatocellular carcinoma (HCC) in the long-term remains unknown. METHODS We included 110 patients into this study. Each patient had fewer than three recurrent HCCs, with the largest tumor less than 5 cm in diameter. Sixty-six patients with 88 tumors were treated by PRFA and 44 patients with 55 tumors were treated by repeat hepatectomy. RESULTS The 1-, 2-, 3-, 4-, and 5-year overall survival rates after repeat hepatectomy and PRFA were 78.6%, 56.8%, 44.5%, 30.7%, and 27.6%, and 76.6%, 48.6%, 48.6%, 39.9%, and 39.9%, respectively (P = 0.79). The 1-, 2-, 3-, 4-, and 5-year overall survival rates after the initial hepatectomy for the two groups were 95.4%, 79.1%, 65.0%, 50.4%, and 42.9%, and 98.5%, 85.0%, 70.8%, 58.7%, and 55.6%, respectively, (P = 0.18). Subgroup analyses showed that there was no significant difference between the overall survivals of the two groups of patients when the interval of tumor recurrence from the initial hepatectomy was <or=1 year (P = 0.74) or >1 year (P = 0.69), and for recurrent tumor <or=3 cm (P = 0.62) or >3 cm (P = 0.57). Major complications happened significantly more often after repeat hepatectomy than PRFA (30 of 44 versus 2 of 66, P < 0.05). The interval of recurrence from the initial hepatectomy, the diameter of the recurrent tumor and the serum albumin level were significant prognostic factors for overall survival. CONCLUSION PRFA was as effective as repeat hepatectomy in the treatment of recurrent small HCC. PRFA had the advantage over repeat hepatectomy in being less invasive.
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Affiliation(s)
- Hui-Hong Liang
- State Key Laboratory of Oncology in Southern China, Guangzhou, People's Republic of China
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Luo KZ, Itamoto T, Amano H, Oshita A, Ushitora Y, Tanimoto Y, Ohdan H, Tashiro H, Asahara T. Comparative study of the Japan Integrated Stage (JIS) and modified JIS score as a predictor of survival after hepatectomy for hepatocellular carcinoma. J Gastroenterol 2008; 43:369-77. [PMID: 18592155 DOI: 10.1007/s00535-008-2164-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2007] [Accepted: 01/23/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The purpose of the study was to compare the abilities of the JIS and modified JIS (m-JIS) scores to predict survival after hepatectomy for hepatocellular carcinoma (HCC). METHODS Data for patients who underwent hepatectomy for HCC at Hiroshima University Hospital between 1986 and 2006 were included. The overall survival and disease-free survival were calculated by the Kaplan-Meier method, and differences between groups were tested by the log-rank test. The statistics of the Akaike information criterion (AIC) were used to show the more appropriate model. RESULTS A total of 626 patients were included (male/female, 468/158; mean age, 63.4+/-9.6 years; Child-Pugh class A/B, 524/102; liver damage grade A/B/C, 356/261/9). Mean survival and disease-free survival were 8.04+/-0.39 and 4.69+/-0.32 years, respectively. There was a significant difference in the overall survival rate between JIS scores 1 and 2, and 2 and 3 (P<0.05), but not between scores 0 and 1, or 3 and 4 (P>0.05). Except between m-JIS scores 0 and 1, there was excellent discriminatory ability in overall survival rate between other consecutive groups. Concerning disease-free survival, a significant difference was found only between JIS scores 1 and 2. However, the disease-free survival rate could be well differentiated between m-JIS scores 1 and 2, and 3 and 4. The m-JIS score had a higher discriminatory ability, indicated by a linear trend analysis, and a higher homogeneity likelihood ratio, and lower AIC statistics, than the original JIS score in predicting both overall and disease-free survival. CONCLUSIONS The modified-JIS scoring system using liver damage grade is better than the original JIS scoring system in predicting survival after hepatectomy for HCC in Japan.
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Affiliation(s)
- Kai-Zhong Luo
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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