|
1
|
Bannister ME, Chatterjee DA, Shetty S, Patten DA. The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential. Int J Mol Sci 2024; 25:13167. [PMID: 39684877 DOI: 10.3390/ijms252313167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents a significant clinical burden globally and is predicted to continue to increase in incidence for the foreseeable future. The treatment of HCC is complicated by the fact that, in the majority of cases, it develops on a background of advanced chronic inflammatory liver disease. Chronic inflammation can foster an immunosuppressive microenvironment that promotes tumour progression and metastasis. In this setting, macrophages make up a major immune component of the HCC tumour microenvironment, and in this review, we focus on their contribution to HCC development and progression. Tumour-associated macrophages (TAMs) are largely derived from infiltrating monocytes and their potent anti-inflammatory phenotype can be induced by factors that are found within the tumour microenvironment, such as growth factors, cytokines, hypoxia, and extracellular matrix (ECM) proteins. In general, experimental evidence suggest that TAMs can exhibit a variety of functions that aid HCC tumour progression, including the promotion of angiogenesis, resistance to drug therapy, and releasing factors that support tumour cell proliferation and metastasis. Despite their tumour-promoting profile, there is evidence that the underlying plasticity of these cells can be targeted to help reprogramme TAMs to drive tumour-specific immune responses. We discuss the potential for targeting TAMs therapeutically either by altering their phenotype within the HCC microenvironment or by cell therapy approaches by taking advantage of their infiltrative properties from the circulation into tumour tissue.
Collapse
Affiliation(s)
- Megan E Bannister
- Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK
| | - Devnandan A Chatterjee
- Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK
- National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK
| | - Shishir Shetty
- Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK
- National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK
| | - Daniel A Patten
- Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK
| |
Collapse
|
|
2
|
Topolewski P, Łaski D, Łukasiewicz M, Domagała P, de Wilde RF, Polak WG. Response to Bridging Therapy as a Prognostic Indicator of Post-Transplantation Hepatocellular Carcinoma Recurrence and Survival: A Systematic Review. Cancers (Basel) 2024; 16:3862. [PMID: 39594819 PMCID: PMC11592521 DOI: 10.3390/cancers16223862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/02/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC) in cirrhotic livers. Neoadjuvant bridging treatment in patients qualifying and listed for LT is advised but is still debatable owing to the low level of evidence. The aim of this study was to perform a systematic review to assess the prognostic value of bridging therapy, in terms of radiological and histopathological examination outcomes, for survival after LT. The systematic review was performed according to the PRISMA 2020 guidelines. The MEDLINE and Web of Science databases were searched. In total, five studies were included. An evaluation with the ROBINS-I resulted in studies classified as the following: moderate risk of bias (n = 1) and serious risk of bias (n = 4). The results of the analysis indicated that favorable LT outcomes were most common with complete response or partial radiological response. Poor radiological response or progressive disease during bridging treatment was generally associated with worse overall LT survival. There were not enough data to support the use of this approach to achieve a complete pathologic response. Radiological, pathological, histological, cellular, and molecular tumor features should be included in future LT qualification models.
Collapse
Affiliation(s)
- Paweł Topolewski
- Division of Quality in Healthcare, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Dariusz Łaski
- Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Martyna Łukasiewicz
- Division of Quality in Healthcare, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Piotr Domagała
- Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Roeland F. de Wilde
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of HPB- & Transplant Surgery, 3015 GD Rotterdam, The Netherlands
| | - Wojciech G. Polak
- Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk, 80-210 Gdańsk, Poland
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of HPB- & Transplant Surgery, 3015 GD Rotterdam, The Netherlands
| |
Collapse
|
|
3
|
Gani RA, Teressa M, Budiman RA, Kalista KF, Lesmana CRA. Meta analysis of radiofrequency ablation versus surgical resection in small and large nodule of hepatocellular carcinoma. HPB (Oxford) 2024; 26:1216-1228. [PMID: 39060212 DOI: 10.1016/j.hpb.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/21/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024]
Abstract
INTRODUCTION Although studies have indicated comparable outcomes between RFA and surgical resection in early HCC, there is still unclear evidence of benefit in larger tumor sizes. This study aimed to assess the efficacy and safety of RFA versus surgical resection in HCC patients, considering nodule size with a cutoff at 3 cm. METHODS A comprehensive search of multiple databases was conducted. The systematic review and meta-analysis followed the PRISMA guidelines. RESULT Surgical resection showed superior OS (HR = 1.18, 95% CI: 1.11-1.27, p = 0.008) and RFS (HR = 1.17, 95% CI: 1.11-1.25, p < 0.00001), compared to RFA. For nodules less than 3 cm or larger than 5 cm, the OS and RFS in the surgical resection group were significantly higher than those in the RFA group, while no significant differences were observed for nodules sized 3-5 cm. However, significantly more adverse events occurred following surgical resection (OR = 0.43, 95% CI: 0.33-0.56, P < 0.00001). CONCLUSION Surgical resection has better OS and RFS compared to RFA for liver tumors less than 3 cm or larger than 5 cm. For liver tumors sized 3-5 cm, RFA and surgical resection yield similar findings. RFA may become a preferable option in these 3-5 cm tumors due to its comparable efficacy and fewer adverse events for patients unsuitable for surgery.
Collapse
Affiliation(s)
- Rino A Gani
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
| | - Maria Teressa
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Refael A Budiman
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Kemal F Kalista
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Cosmas Rinaldi A Lesmana
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| |
Collapse
|
|
4
|
Cai Z, Zhang J, He Y, Xia L, Dong X, Chen G, Zhou Y, Hu X, Zhong S, Wang Y, Chen H, Xie D, Liu X, Liu J. Liquid biopsy by combining 5-hydroxymethylcytosine signatures of plasma cell-free DNA and protein biomarkers for diagnosis and prognosis of hepatocellular carcinoma. ESMO Open 2021; 6:100021. [PMID: 33508734 PMCID: PMC7841321 DOI: 10.1016/j.esmoop.2020.100021] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/29/2020] [Accepted: 11/14/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Liquid biopsy based on 5-hydroxymethylcytosine (5hmC) signatures of plasma cell-free DNA (cfDNA) originating from tumor cells provides a novel approach for early diagnosis in hepatocellular carcinoma (HCC). Here, we sought to develop a reliable model using cfDNA 5hmC signatures and protein biomarkers for diagnosis and prognosis of HCC. PATIENTS AND METHODS We carried out genome-wide 5hmC sequencing of cfDNA samples collected from 165 healthy volunteers, 62 liver cirrhosis (LC) patients and 135 HCC patients. A sensitive 5hmC diagnostic model was developed based on 5hmC signatures selected by sparse Partial Least Squares Discriminant Analysis and cross-validation to define the weighted diagnostic score (wd-score). Then, we combined protein biomarkers with the wd-score to build a more robust score (HCC score) by logistic regression. RESULTS The distribution pattern of differential 5hmC regions could clearly distinguish HCC patients, LC patients and healthy volunteers. The wd-score based on 64 5hmC signatures in cfDNA achieves 93.24% of area under the curve (AUC) to distinguish HCC patients from non-HCC patients, and the HCC score by combing protein biomarkers achieves 92.75% of AUC to distinguish HCC patients from LC patients. Meanwhile, the HCC score showed high capacity for screening high recurrence risk patients after receiving surgical resection, and appeared to be an independent indicator for both relapse-free survival (P = 0.00865) and overall survival (P = 0.000739). Furthermore, the values of the HCC score in patients' longitudinal plasma samples were positively associated with tumor burden dynamics during follow-up. CONCLUSION We have developed and validated a novel non-invasive liquid biopsy strategy for HCC diagnosis, prognosis and surveillance during HCC progression.
Collapse
Affiliation(s)
- Z Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China
| | - J Zhang
- Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, P. R. China
| | - Y He
- Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, P. R. China; Laboratory of Nervous System Disease and Brain Functions, Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, P. R. China
| | - L Xia
- Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, P. R. China
| | - X Dong
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China
| | - G Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China
| | - Y Zhou
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China
| | - X Hu
- Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, P. R. China
| | - S Zhong
- Tailai Inc., Shanghai, P. R. China
| | - Y Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China
| | - H Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China
| | - D Xie
- Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, P. R. China.
| | - X Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China.
| | - J Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China; Mengchao Med-X Center, Fuzhou University, Fuzhou, P. R. China.
| |
Collapse
|
|
5
|
Lai Y, Lee JC, Hung HC, Cheng CH, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC. Models to predict disease-free survival for hepatocellular carcinoma patients with surgical resections. J Surg Oncol 2020; 122:1444-1452. [PMID: 32875573 DOI: 10.1002/jso.26169] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 07/27/2020] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND OBJECTIVES Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001). CONCLUSION Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection.
Collapse
Affiliation(s)
- Yin Lai
- Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| |
Collapse
|
|
6
|
Shin IS, Kim DG, Cha SW, Kang SH, Kim SH, Kim MY, Baik SK. Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age? Ann Surg Treat Res 2020; 99:65-71. [PMID: 32802811 PMCID: PMC7406395 DOI: 10.4174/astr.2020.99.2.65] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 05/02/2020] [Accepted: 05/12/2020] [Indexed: 02/08/2023] Open
Abstract
Purpose Elderly individuals have comorbidities that can adversely affect surgical outcomes. Some studies reported that elderly patients with hepatocellular carcinoma (HCC) have higher liver- and non-liver-related deaths. Therefore, palliative treatments are preferred in these patients. We compared surgical treatment outcomes between young and old age groups. Methods In total, 233 liver resections were performed in patients with HCC from March 2012 to December 2018. We retrospectively reviewed medical records. The old age group was defined as patients aged more than 70 years. We compared perioperative characteristics and surgical outcomes and analyzed the prognostic factors for disease-free survival (DFS) and overall survival (OS) rates. Results The young and old age group included 184 and 49 patients, respectively. Preoperative characteristics were similar. Major liver resection rate was similar (young age group, 26.1% vs. old age group, 20.4%), but the operation time was a little bit shorter in old age group. Major postoperative complications were 23 (12.5%) and 9 (18.4%) in the young and old age group (P = 0.351). Median non-liver-related overall survival were 80 and 76 months (P = 0.889) and liver-related OS were 76 and 76 months (P = 0.514) in the young and old age groups, respectively. Age was not an independent risk factor for DFS and OS. Conclusion Elderly patients showed similar non-liver- and liver-related OS rates as young patients after liver resection. Postoperative complications were also similar. If elderly patients are well selected, they can receive curative treatment and show good surgical outcomes.
Collapse
Affiliation(s)
- In Sik Shin
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Deok Gie Kim
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sung Whan Cha
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sung Hoon Kim
- Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| |
Collapse
|
|
7
|
Liu YW, Lin CC, Yong CC, Wang CC, Chen CL, Wang JH, Yen YH. Prognosis after resection of single large hepatocellular carcinoma: Results from an Asian high-volume liver surgery center. PLoS One 2020; 15:e0230897. [PMID: 32218593 PMCID: PMC7100934 DOI: 10.1371/journal.pone.0230897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/11/2020] [Indexed: 02/08/2023] Open
Abstract
Background & aims In 2012, the Barcelona Clinic Liver Cancer (BCLC) system designated a single large hepatocellular carcinoma (SLHCC) (>5 cm) as BCLC stage A rather than stage B. However, a recent study from western countries reported that prognosis following liver resection (LR) among patients with SLHCC was similar to that among patients with BCLC stage B. We aim to evaluate the prognosis following LR among patients with SLHCC from an Asian high-volume liver surgery center. Methods Patients who underwent curative-intent LR for histologically proven HCC between 2011 and 2017 were enrolled using an HCC registry database. Overall survival (OS) among patients with BCLC stages 0, A, and B was examined. Patients with a SLHCC were classified as BCLC stage A1. Results Among 543 patients, 89 (16.4%) were BCLC stage 0, 289 (53.2%) were BCLC stage A, 92 (16.9%) were BCLC stage A1, and 73 (13.4%) were BCLC stage B. The median follow-up was 38 months. The five-year OS rates among patients with BCLC stages 0, A, A1, and B were 83.5%, 83.7%, 77.4%, and 55.4%, respectively (p<0.001). No difference in OS was noted for patients with BCLC stage A versus A1 (p = 0.11), even after adjusting for competing factors (hazard ratio = 0.97, 95% confidence interval = 0.53–1.79; p = 0.93). Conclusion Prognosis following LR among patients with SLHCC was similar to that among patients with BCLC stage A. The prognosis for SLHCC should thus be considered comparable to that for BCLC stage A.
Collapse
Affiliation(s)
- Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
| |
Collapse
|
|
8
|
Jia C, Ge K, Xu S, Liu L, Weng J, Chen Y. Selective occlusion of the hepatic artery and portal vein improves liver hypertrophy for staged hepatectomy. World J Surg Oncol 2019; 17:167. [PMID: 31590665 PMCID: PMC6781355 DOI: 10.1186/s12957-019-1710-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 09/10/2019] [Indexed: 12/23/2022] Open
Abstract
Background To evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC) Methods From December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded. Results In the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively. Conclusion SOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.
Collapse
Affiliation(s)
- Changku Jia
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, No. 261, Huansha Road, Hangzhou, 310006, China.
| | - Ke Ge
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, No. 261, Huansha Road, Hangzhou, 310006, China
| | - Sunbing Xu
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, No. 261, Huansha Road, Hangzhou, 310006, China.
| | - Ling Liu
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, No. 261, Huansha Road, Hangzhou, 310006, China
| | - Jie Weng
- Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Hainan Medical College, Haikou, 570102, China
| | - Youke Chen
- Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Hainan Medical College, Haikou, 570102, China
| |
Collapse
|
|
9
|
Aseni P, Di Domenico SL, Barbosa F, Rampoldi A, Berry C. Hemoperitoneum in cirrhotic patients in the absence of abdominal trauma. Expert Rev Gastroenterol Hepatol 2019; 13:867-876. [PMID: 31204541 DOI: 10.1080/17474124.2019.1631159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Hemoperitoneum can be a life-threating condition in cirrhotic patients who have a limited compensatory reserve during hemorrhagic shock. We aim to review the literature on the different etiologies associated with non-traumatic hemoperitoneum (NTH), summarizing the most relevant conditions associated with spontaneous and iatrogenic peritoneal and retroperitoneal bleeding that may occur in cirrhotic patients and to illustrate the most relevant diagnostic strategies and optimal management. Area covered: This review encompasses the current literature in hemoperitoneum in cirrhotic patients in the absence of abdominal trauma. Established diagnostic procedures, therapeutic interventions and potential novel targets are reported and discussed. Expert opinion: To ensure the optimal management regardless of the underlying etiology of NTH, the first goal for the clinician is to obtain immediate hemodynamic stabilization with supportive measures and to control the source of bleeding. The latter can be achieved with angiographic embolization, which is usually the first choice, or with open surgery. Other therapeutic options according to specific etiologies include transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), balloon-occluded anterograde transvenous obliteration (BATO) or intra operative radio frequency (RF).
Collapse
Affiliation(s)
- Paolo Aseni
- Department of Emergency, ASST Grande Ospedale Metropolitano Niguarda , Milan , Italy
| | | | | | | | - Cherisse Berry
- Department of Surgery, Division of Acute Care Surgery, New York University School of Medicine , New York , NY , USA
| |
Collapse
|
|
10
|
Wu L, Yang Z, Zhang J, Xie H, Zhou L, Zheng S. Long noncoding RNA HOTTIP expression predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Hepatobiliary Surg Nutr 2018; 7:429-439. [PMID: 30652087 DOI: 10.21037/hbsn.2018.10.07] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma (HCC). Methods In the present study, we evaluated the clinical significance of HOTTIP expression in predicting the rate of tumor recurrence in HCC patients after liver transplantation (LT). We examined the expression pattern and single nucleotide polymorphism (SNP) genotype of HOTTIP in HCC samples from 155 patients underwent LT, and its correlation with clinical parameters and patient prognosis was analyzed. HOTTIP was suppressed using siRNA to explore the role HOTTIP plays in tumor progression. Results The expression level of HOTTIP in cancer tissues was higher than in adjacent noncancerous tissues. Multivariate analyses revealed that HOTTIP expression was an independent prognostic factor for tumor recurrence and lower overall survival times in HCC patients after LT. Patients who beyond the Milan criteria and exhibit decreased HOTTIP expression experienced longer recurrence-free survival and overall survival. HOTTIP rs2071265 is associated with an earlier recurrence in HCC patients. Moreover, the suppression of HOTTIP in liver cancer cell lines reduced cell invasion rates and increased chemosensitivity. Conclusions In summary, the high expression level of HOTTIP in HCC could serve as a candidate biomarker for predicting poor prognosis in HCC patients underwent liver transplant therapy. Furthermore, HOTTIP might be a potential therapeutic target.
Collapse
Affiliation(s)
- Liming Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.,Jingning National Hospital of the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, First Hospital of Jiaxing, Jiaxing University, Jiaxing 314000, China
| | - Haiyang Xie
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| |
Collapse
|
|
11
|
Wu L, Yang F, Lin B, Chen X, Yin S, Zhang F, Xie H, Zhou L, Zheng S. MicroRNA-424 expression predicts tumor recurrence in patients with hepatocellular carcinoma following liver transplantation. Oncol Lett 2018; 15:9126-9132. [PMID: 29805644 PMCID: PMC5958633 DOI: 10.3892/ol.2018.8539] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Accepted: 10/20/2017] [Indexed: 12/15/2022] Open
Abstract
MicroRNA-424 (miR-424) has previously been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma (HCC). In the present study, the clinical significance of miR-424 expression in predicting the rate of tumor recurrence in patients with HCC following liver transplantation (LT) was evaluated. miR-424 expression in HCC samples from 121 patients undergoing LT was examined, and the associations between clinical parameters and patient tumor recurrence were evaluated. The miR-424 expression level in cancer tissues was low compared with that in adjacent noncancerous tissues. Multivariate analyses revealed that low miR-424 expression was an independent prognostic factor for tumor recurrence in patients with HCC following liver transplantation. Patients who no longer met the Milan criteria and had decreased miR-424 expression levels exhibited earlier tumor recurrence following LT. In addition, the upregulation of miR-424 expression significantly reduced the migration, invasion and proliferation of HCC cells. Similarly, the downregulation of miR-424 in HCC cells significantly promoted the migration, invasion and proliferation of HCC cells.
Collapse
Affiliation(s)
- Liming Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Ningbo, Zhejiang 315100, P.R. China
| | - Feibiao Yang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Ningbo, Zhejiang 315100, P.R. China.,Department of Hepatobiliary Surgery, Yinzhou People's Hospital of Ningbo City, Ningbo, Zhejiang 315100, P.R. China
| | - Bingyi Lin
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Ningbo, Zhejiang 315100, P.R. China
| | - Xinhua Chen
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Ningbo, Zhejiang 315100, P.R. China
| | - Shengyong Yin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China
| | - Feng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China
| | - Haiyang Xie
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ningbo, Zhejiang 315100, P.R. China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Ningbo, Zhejiang 315100, P.R. China
| |
Collapse
|
|
12
|
Wang J, Lian Y, Gu Y, Wang H, Gu L, Huang Y, Zhou L, Huang Y. Synergistic effect of farnesyl transferase inhibitor lonafarnib combined with chemotherapeutic agents against the growth of hepatocellular carcinoma cells. Oncotarget 2017; 8:105047-105060. [PMID: 29285232 PMCID: PMC5739619 DOI: 10.18632/oncotarget.22086] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 10/12/2017] [Indexed: 12/29/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide and is often refractory to chemotherapy due to the development of multidrug resistance. Lonafarnib is an orally active and potent non-peptidomimetic inhibitor of farnesyl transferase. Here, using in vitro HCC cell models, we demonstrated that lonafarnib inhibited tumor proliferation and reduced the activity of mitogen-activated protein kinases pathways. In addition, lonafarnib caused G1 to S phase arrest through the downregulation of Cyclin D1, CDK6 and SKP2, while it induced cellular apoptosis by promoting the cleavage and activation of Caspase-3 and PARP. When combined with doxorubicin and sorafenib, lonafarnib was able to increase the sensitivity of HCC cells to chemotherapy. Furthermore, we also constructed ABCB1-overexpressing HCC cells and found that lonafarnib decreased chemoresistance by inhibiting ABCB1-mediated drug efflux activity. These results suggest that lonafarnib may be a promising synergistic agent for improving the treatment of drug-resistant HCC.
Collapse
Affiliation(s)
- Jialiang Wang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yifan Lian
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yurong Gu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hongbo Wang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lin Gu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yanlin Huang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liang Zhou
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuehua Huang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
13
|
Feng J, Chen J, Zhu R, Yu L, Zhang Y, Feng D, Kong H, Song C, Xia H, Wu J, Zhao D. Prediction of early recurrence of hepatocellular carcinoma within the Milan criteria after radical resection. Oncotarget 2017; 8:63299-63310. [PMID: 28968990 PMCID: PMC5609922 DOI: 10.18632/oncotarget.18799] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 06/02/2017] [Indexed: 02/07/2023] Open
Abstract
Approximately 50% hepatocellular carcinoma patients meeting the Milan criteria utilized to develop an improved prognostic model for predicting the recurrence in these patients. Using univariate and multivariate analysis, cytokeratin-19 and glypican-3 expression patterns, tumor number and histological grading from eight putative prognostic factors comprised the risk factor scoring model to predict the tumor recurrence. In the training cohort, the area under roc curve (AUC) value of the model was 0.715 [95% confidence interval (CI) = 0.645-0.786, P<0.001], which was the highest among all the parameters. The performance of the model was assessed using an independent validation cohort, wherein the AUC value was 0.760 (95% CI=0.647-0.874, P<0.001), which was higher than the other factors. The results indicated that model had high performance with adequate discrimination ability. Moreover, it significantly improved the predictive capacity for the recurrence in patients with hepatocellular carcinoma within the Milan criteria after radical resection.
Collapse
Affiliation(s)
- Jiliang Feng
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Junmei Chen
- Medical Laboratory Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Ruidong Zhu
- Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lu Yu
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Yan Zhang
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Dezhao Feng
- College of Life Science, Sichuan University, Chengdu, China
| | - Heli Kong
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Chenzhao Song
- Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Hui Xia
- Surgical Center, The 304th Hospital of PLA, Beijing, China
| | - Jushan Wu
- Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Dawei Zhao
- Medical Imaging Department, Beijing You-An Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
14
|
Pan X, Li X, Cui L, Wang Q. Preoperative Phenacetin Metabolism Test in the Prediction of Postoperative Liver Dysfunction of Patients with Hepatocellular Carcinoma. Med Sci Monit 2017; 23:2607-2611. [PMID: 28553832 PMCID: PMC5461888 DOI: 10.12659/msm.905228] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The risk of postoperative liver dysfunction (PLD) in patients with injured livers, such as in hepatocellular carcinoma (HCC), is still not negligible. Phenacetin metabolism test can reflect hepatic functional reserve in patients with chronic hepatic damage. The aim of this study was to assess the ability of phenacetin metabolism test to predict PLD in patients with HCC receiving partial hepatectomy. MATERIAL AND METHODS Forty-nine patients with HCC undergoing partial hepatectomy between 2014 and 2016 were included at Huashan Hospital, Fudan University. The phenacetin metabolism test was used to assess the hepatic functional reserve. The ratio of total plasma paracetamol to phenacetin was collected in patients at 2 h after oral administration of 1.0 g phenacetin, recorded 5 days prior to surgery and on the fifth postoperative day. Phenacetin metabolism test, Child-Pugh classification, and Model for End-Stage Liver Disease (MELD) score were correlated with PLD. RESULTS Of 49 patients with HCC, 13 patients (26.5%) had PLD. The association between the ratio of total plasma paracetamol to phenacetin and PLD was statistically significant (p=0.0061) and the correlation coefficient was -0.647 (p=0.0082). The phenacetin metabolism test showed a larger area under the receiver operating characteristic (ROC) curve value (0.735) than Child-Pugh's classification (0.472) and MELD score (0.419). Using the calculated cutoff of 0.6, the lower ratio of total plasma paracetamol to phenacetin preoperatively was chosen to specifically identify patients with PLD. The sensitivity and specificity were 0.657 and 0.892, respectively. CONCLUSIONS Phenacetin metabolism test could be preoperatively used in predicting PLD in HCC patients receiving partial hepatectomy. It potentially provides better prediction than Child-Pugh classification and MELD score.
Collapse
Affiliation(s)
- Xiaohua Pan
- Department of Operation Room, Huashan Hospital North, Fudan University, Shanghai, China (mainland)
| | - Xiaodong Li
- Cancer Institute, Second Military Medical University, Shanghai, China (mainland)
| | - Liqing Cui
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland)
| | - Qianwei Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China (mainland)
| |
Collapse
|
|
15
|
Feasibility of Preoperative FDG PET/CT Total Hepatic Glycolysis in the Remnant Liver for the Prediction of Postoperative Liver Function. AJR Am J Roentgenol 2016; 208:624-631. [PMID: 28026972 DOI: 10.2214/ajr.16.16450] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The objective of our study was to investigate the prognostic value of total glycolysis of the remnant liver, which reflects both metabolic and anatomic liver function, for predicting postoperative hepatic insufficiency. MATERIALS AND METHODS Patients who underwent 18F-FDG PET/CT and abdominal CT within 1 month of major hepatectomy were retrospectively analyzed. Total liver volume, remnant liver volume, the ratio of the remnant hepatic volume to the preoperative hepatic volume (RFRHV), and mean standardized uptake value (SUVmean) were measured, and total glycolysis of the remnant liver was calculated. Clinical hepatic function reserve values, including the indocyanine green retention rate at 15 minutes, the model for end-stage liver disease (MELD) score, and aspartate aminotransferase to platelet ratio index (APRI), were calculated. Univariate and multivariate analyses were performed, and an optimal model for predicting hepatic insufficiency was developed. ROC curves were used to compare diagnostic performance. RESULTS Of 149 patients, seven patients had hepatic insufficiency. The SUVmean showed the highest sensitivity (100%; specificity, 31.7%) for predicting hepatic insufficiency, and total glycolysis of the remnant liver showed the highest specificity (96.5%; sensitivity, 57.1%) for predicting hepatic insufficiency. On multivariate analysis, the odds ratio of APRI (> 5.4) and total glycolysis of the remnant liver (≤ 625.6) was 46.3 and 82.9, respectively, for predicting hepatic insufficiency. On ROC curve analysis, a new model composed of APRI and total glycolysis of the remnant liver showed a higher area under the ROC curve (Az) value (Az = 0.899) than SUVmean (0.659), MELD score (0.618), APRI (0.693), RFRHV (0.797), and remnant liver volume (0.762). CONCLUSION The total glycolysis of the remnant liver has moderate sensitivity and high specificity for predicting hepatic insufficiency. Combining the total glycolysis of the remnant liver and APRI yielded the best diagnostic performance for predicting hepatic insufficiency.
Collapse
|
|
16
|
Diffusion-weighted imaging of hepatocellular carcinomas: a retrospective analysis of correlation between apparent diffusion coefficients and histological grade. Abdom Radiol (NY) 2016; 41:1539-45. [PMID: 27003574 DOI: 10.1007/s00261-016-0715-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To define correlations between the pathological grades of hepatocellular carcinomas (HCCs) and apparent diffusion coefficients (ADCs) derived using breath-holding diffusion-weighted imaging (BH-DWI). METHODS We retrospectively evaluated 94 patients (105 lesions) with pathologically proved HCC who underwent hepatic DWI on a 3.0-T MR platform. HCCs were divided into five groups: well-differentiated (n = 10), well-to-moderately differentiated (n = 11), moderately differentiated (n = 51), moderately to poorly differentiated (n = 20), and poorly differentiated (n = 13) groups. The ADCs of carcinomas across different histological grades were compared by one-way analysis of variance. Spearman's rank correlation test was used to analyze correlations between the degree of histopathological differentiation and ADC. Results were corrected for multiple comparisons using the Bonferroni correction. RESULTS The BH technique yielded ADC values that differed significantly by the extent of differentiation (F = 8.392, p < 0.001). A significant negative correlation was found between the extent of differentiation and ADCs (r = -0.462, p < 0.001). The mean ADC values of poorly differentiated HCCs were significantly lower than the well-, well-to-moderately, moderately, and moderately to poorly differentiated HCCs (p values were <0.001, <0.001, 0.003, and 0.031, respectively). CONCLUSION ADC values obtained with BH-DWI may be of importance to non-invasively predict HCC tumor differentiation, and the extent of histological HCC differentiation was inversely correlated with ADC values.
Collapse
|
|
17
|
Strassburg CP. HCC-Associated Liver Transplantation - Where Are the Limits and What Are the New Regulations? Visc Med 2016; 32:263-271. [PMID: 27722163 DOI: 10.1159/000446385] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) represents an increasing health burden worldwide and a challenging disease both in terms of diagnosis and treatment. METHODS The literature available on PubMed for the period of 1990-2016 was reviewed with reference to liver allocation, HCC, liver transplantation (LT), and prediction, and the allocation rules of the German Transplant Act were reviewed. RESULTS Due to etiological and geographical diversity, HCC is not a homogeneous disease. In the vast majority of patients, HCC develops as a complication of chronic liver disease and cirrhosis. While most patients present with advanced HCC for which palliative strategies are the only available option, LT is the best treatment approach as it not only eliminates the diseased liver and the underlying hepatocarcinogenic mechanisms but also the cancer. The decision for LT is not an easy one to make, because outcome prediction, staging, bridging therapy, and recurrence prevention are difficult and are estimated against the background of the scarce resource of donor organs which are also competitively sought after by patients suffering from non-neoplastic terminal liver diseases, raising the issue of equality of chances in a rationed therapeutic modality. Currently, the Milan criteria are the best evaluated decision tool for LT, but many issues such as down-staging, favorable biological behavior during treatment, expansion of the morphological classification, molecular predictors, and individualized approaches are not yet satisfactorily addressed. CONCLUSION In order to provide a fair and effective approach to LT in HCC, the employed allocation rules require continuous development and scientific evaluation. Recently, the allocation rules for standard exception priority according to the German Transplant Act have been revised to improve patient selection for LT in HCC.
Collapse
|
|
18
|
Mazzanti R, Arena U, Tassi R. Hepatocellular carcinoma: Where are we? World J Exp Med 2016; 6:21-36. [PMID: 26929917 PMCID: PMC4759352 DOI: 10.5493/wjem.v6.i1.21] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 12/14/2015] [Accepted: 01/05/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called "up to seven criteria" to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.
Collapse
|