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Liu M, Liu Y, Zhou W, Pan F, Chen M, Xie X, Zhou L. Contrast-enhanced US versus US-guided biopsy for abdominal and pelvic neoplasm in paediatric patients: a propensity score matching study. Eur Radiol 2025; 35:1001-1011. [PMID: 39143246 DOI: 10.1007/s00330-024-11018-6] [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: 02/06/2024] [Revised: 06/06/2024] [Accepted: 07/31/2024] [Indexed: 08/16/2024]
Abstract
OBJECTIVE To compare the diagnostic performance of CEUS-guided biopsy (CEUS-GB) and ultrasound-guided biopsy (US-GB) in evaluating abdominal and pelvic (abdominopelvic) neoplasms in paediatric patients. METHODS Patients aged < 18 years with abdominopelvic tumours who underwent either CEUS-GB or US-GB between April 2005 and May 2022 were retrospectively evaluated. Tumours diagnosed as malignancies by pathology were considered true-positive findings. Benign lesions were identified by pathology or clinical follow-up of at least 6 months. The diagnostic performance of the two groups was compared using propensity score matching (PSM). Complications were also analysed. RESULTS The present study included 764 paediatric patients (437 boys; median age, 24 months; interquartile range, 10-60 months); 151 were in the CEUS-GB group, and 613 were in the US-GB group. The sample adequacy rate was 100% (151 of 151) for the CEUS-GB group, which was greater than the 97.4% (597 of 613) for the US-GB group (p < 0.001). The overall diagnostic accuracy of the CEUS-GB group and US-GB group was 98.7% (149 of 151) versus 97.3% (581 of 597) in the total cohort (p = 0.551) and 98.7% (149 of 151) versus 92.7% (140 of 151) in the PSM cohort (p = 0.020). Two patients (0.3%) in the US-GB group experienced complications (Common Terminology Criteria for Adverse Events (CTCAE), grade 1-2) correlated with the biopsy. No adverse reactions occurred in the CEUS-GB group. CONCLUSION CEUS-GB of abdominopelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-GB, especially for tumours with necrotic areas. CLINICAL RELEVANCE STATEMENT Contrast-enhanced US-guided biopsy of solid abdominal and pelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-guided biopsy, especially for tumours with necrotic areas. KEY POINTS Contrast-enhanced ultrasound (CEUS) may be superior to conventional ultrasound at guiding biopsy of abdominopelvic masses in paediatric patients. CEUS-guided core needle biopsy of abdominopelvic masses in children was safe and resulted in a diagnostic yield of 98.7%. CEUS guidance should be considered in this population when colour Doppler US is unable to determine a biopsy site.
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Affiliation(s)
- Ming Liu
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Yingxin Liu
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Wenying Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Fushun Pan
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Meixi Chen
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan Er Road, 510080, Guangzhou, P.R. China.
- Department of Ultrasound, Shenzhen Children' Hospital, No. 7019, Yitian Road, Futian District, 518026, Shenzhen, P.R. China.
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Etiology, Pathogenesis, Diagnosis, and Practical Implications of Hepatocellular Neoplasms. Cancers (Basel) 2022; 14:cancers14153670. [PMID: 35954333 PMCID: PMC9367411 DOI: 10.3390/cancers14153670] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/18/2022] [Accepted: 07/25/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features and prognosis, suggesting that subclassification of HCC is practically useful. On the other hand, subclassification of hepatocellular adenomas (HCAs), a heterogenous group of neoplasms, has been well established on the basis of genotype–phenotype correlations. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of HCA and HCC, while clinicopathologic correlation is essential for best patient management. Advances in clinico-radio-pathologic correlation have introduced a new approach for the diagnostic assessment of lesions arising in advanced chronic liver disease by imaging (LI-RADS). The rapid expansion of knowledge concerning the molecular pathogenesis of HCC is now starting to produce new therapeutic approaches through precision oncology. This review summarizes the etiology and pathogenesis of HCA and HCC, provides practical information for their histologic diagnosis (including an algorithmic approach), and addresses a variety of frequently asked questions regarding the diagnosis and practical implications of these neoplasms.
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Huang JX, Shi CG, Xu YF, Fu J, Zhong Y, Liu LZ, Pei XQ. The benefit of contrast-enhanced ultrasound in biopsies for focal liver lesions: a retrospective study of 820 cases. Eur Radiol 2022; 32:6830-6839. [PMID: 35881185 DOI: 10.1007/s00330-022-08988-w] [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: 02/27/2022] [Revised: 06/15/2022] [Accepted: 06/27/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE This study compared the performance between ultrasound (US)- and contrast-enhanced US (CEUS)-guided liver biopsies and evaluated the benefit of CEUS in percutaneous biopsy for focal liver lesions (FLLs). METHODS We performed a retrospective study of 820 patients with FLLs, who underwent percutaneous liver biopsy in our center between 2017 and 2019. The patients were divided into two groups based on whether US (n = 362) or CEUS (n = 458) used before a biopsy. The two groups were compared based on specimen adequacy for pathological diagnosis and diagnostic accuracy of liver biopsy. Stratification analysis was performed based on lesion and protocol characteristics to provide detailed information for selecting the imaging guidance for biopsy. RESULTS Compared with the US group, the CEUS group yielded more acceptable samples (97.6% vs. 99.4%, p < 0.05) and improved diagnostic accuracy (92.6% vs. 96.4%, p < 0.05), and achieved better sensitivity (92.5% vs. 96.2%, p < 0.05) for liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. The CEUS group showed significantly higher accuracy compared with the US group pertaining to single-puncture biopsies (100% vs. 92.7%, p < 0.05) or biopsies with punctures ≤ 2 (97.6% vs. 94.3%, p < 0.05). CONCLUSION CEUS achieved an enhanced success rate for sampling and diagnostic accuracy of liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. CEUS can be used to decrease the number of punctures needed, which might increase the safety of liver biopsy. KEY POINTS • CEUS can help confirm an adequate biopsy site, increasing the sampling success rate and diagnostic accuracy of the liver biopsy. • CEUS can be used to decrease the number of punctures needed to improve the safety of liver biopsy. • It is recommended to use CEUS guidance for liver biopsies, especially with FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary.
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Affiliation(s)
- Jia-Xin Huang
- Department of Medical Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou, 510000, Guangdong Province, China
| | - Cai-Gou Shi
- Department of Medical Ultrasound, Liuzhou People's Hospital, Liuzhou, 545000, China
| | - Yan-Fen Xu
- Department of Medical Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou, 510000, Guangdong Province, China
| | - Juan Fu
- Department of Medical Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou, 510000, Guangdong Province, China
| | - Yuan Zhong
- Department of Medical Ultrasound, Foshan First People's Hospital, Foshan, 528000, China
| | - Long-Zhong Liu
- Department of Medical Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou, 510000, Guangdong Province, China
| | - Xiao-Qing Pei
- Department of Medical Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou, 510000, Guangdong Province, China.
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Salehi O, Vega EA, Kutlu OC, Lunsford K, Freeman R, Ladin K, Alarcon SV, Kazakova V, Conrad C. Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis. HPB (Oxford) 2022; 24:1100-1109. [PMID: 34969618 DOI: 10.1016/j.hpb.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 11/28/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). METHODS The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. RESULTS 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. DISCUSSION HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Onur C Kutlu
- Department of Surgery, University of Miami Health System, Miller School of Medicine, Miami, FL, USA
| | - Keri Lunsford
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Richard Freeman
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Keren Ladin
- Department of Occupational Therapy and Community Health, Tufts University, Boston, MA, USA
| | - Sylvia V Alarcon
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Vera Kazakova
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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6
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Paradis V. Hepatocellular Carcinomas: Towards a pathomolecular approach. Liver Int 2021; 41 Suppl 1:83-88. [PMID: 34155797 DOI: 10.1111/liv.14867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 02/28/2021] [Indexed: 12/24/2022]
Abstract
Molecular analysis of primary liver malignancies has provided a refinement of the pathological diagnosis of this entity and the identification of an increasing number of tumor subtypes of hepatocellular proliferation, either malignant (hepatocellular carcinomas) or benign (hepatocellular adenomas). Besides the diagnosis, a combined pathomolecular approach can also provide further insights into patient prognosis, and help select patients who can benefit from targeted therapies. Hepatocellular carcinomas define a heterogeneous group of malignant hepatocellular proliferation at various levels: macroscopic, histological and molecular. While most carcinomas occur in patients with chronic liver diseases and advanced fibrosis in the background liver, some arise from the malignant transformation of a pre-existing hepatocellular adenoma. TERT promoter mutations are the most frequent genomic alterations observed in the process of malignancy, and they occur early in the process of liver carcinogenesis. Overall, a more active biopsy strategy should be considered a key step in the management of patients with HCC.
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Affiliation(s)
- Valérie Paradis
- Department of Pathology, Université de Paris, Hôpital Beaujon, Paris, France
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7
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Santambrogio R, Barabino M, D'Alessandro V, Iacob G, Opocher E, Gemma M, Zappa MA. Micronvasive behaviour of single small hepatocellular carcinoma: which treatment? Updates Surg 2021; 73:1359-1369. [PMID: 33821430 DOI: 10.1007/s13304-021-01036-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 03/20/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Microinvasion (MI), defined as infiltration of the portal or hepatic vein or bile duct and intrahepatic metastasis are accurate indicators of a poor prognosis for mall hepatocellular carcinomas (HCC). A previous study showed that intraoperative ultrasound (IOUS) definition of MI-HCC had a high concordance with histological findings. Aim of this study is to evaluate overall survival and recurrence patterns of patients with MI-HCC submitted to hepatic resection (HR) or laparoscopic ablation therapies (LAT). METHODS A total of 171 consecutive patients (78 h; 93 LAT) with single, small HCC (< 3 cm) with a MI pattern at IOUS examination were compared analyzing overall survival and recurrence patterns using univariate and multivariate analysis and weighting by propensity score. RESULTS Overall recurrences were similar in the 2 groups (HR: 51 patients (65%); LAT: 66 patients (71%)). The rate of local tumor progression in the HR group was very low (5 pts; 6%) in comparison to LAT group (22 pts; 24%; p = 0.002). The overall survival curves of HR are significantly better than that of the LAT group (p = 0.0039). On the propensity score Cox model, overall mortality was predicted by the surgical treatment with a Hazard ratio 1.68 (1.08-2.623) (p = 0.022). CONCLUSIONS If technically feasible and in patients fit for surgery, HR with an adequate tumor margin should be preferred to LAT in patients with MI-HCC at IOUS evaluation, to eradicate MI features near the main nodule, which are relatively frequent even in small HCC (< 3 cm).
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Affiliation(s)
- Roberto Santambrogio
- ASST Fatebenefratelli Sacco, Chirurgia Generale Ospedale Fatebenefratelli, Piazza Principessa Clotilde 3, 20121, Milano, Italy.
| | - Matteo Barabino
- Chirurgia Epato-Bilio-Pancreatica Ospedale San Paolo Università Di Milano, Milano, Italy
| | - Valentina D'Alessandro
- ASST Fatebenefratelli Sacco, Chirurgia Generale Ospedale Fatebenefratelli, Piazza Principessa Clotilde 3, 20121, Milano, Italy
| | - Giulio Iacob
- ASST Fatebenefratelli Sacco, Chirurgia Generale Ospedale Fatebenefratelli, Piazza Principessa Clotilde 3, 20121, Milano, Italy
| | - Enrico Opocher
- Chirurgia Epato-Bilio-Pancreatica Ospedale San Paolo Università Di Milano, Milano, Italy
| | - Marco Gemma
- Anestesia E Rianimazione Ospedale Fatebenefratelli, Milano, Italy
| | - Marco Antonio Zappa
- ASST Fatebenefratelli Sacco, Chirurgia Generale Ospedale Fatebenefratelli, Piazza Principessa Clotilde 3, 20121, Milano, Italy
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Liu F, Guo X, Dong W, Zhang W, Wei S, Zhang S, Zhu X, Zhou W, Zhang J, Liu H. Postoperative adjuvant TACE-associated nomogram for predicting the prognosis of resectable Hepatocellular Carcinoma with portal vein Tumor Thrombus after Liver Resection. Int J Biol Sci 2020; 16:3210-3220. [PMID: 33162826 PMCID: PMC7645989 DOI: 10.7150/ijbs.46896] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 09/13/2020] [Indexed: 12/15/2022] Open
Abstract
Background: To explore the effects of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis of HCC patients with Portal Vein Tumor Thrombus (PVTT) undergoing resection, and to develop a PA-TACE-related nomogram for predicting survival individually. Patients and Methods: Two hundred and ninety-three consecutive HCC patients with PVTT under R0 hepatectomy were recruited. Forty-seven cases had recurrence within one month after surgery. The remaining 246 cases consisted of 90 PA-TACE and 156 non-PA-TACE cases. COX regression analysis was performed for overall survival (OS) or recurrence-free survival (RFS) of these 246 cases, allowing the derivation of independent factors that were integrated into the nomogram. C-index, calibration curves, and risk stratification were performed to evaluate the performance and discriminative power of the nomograms. Results: In 246 patients without recurrence within one month after surgery, the OS and RFS for the PA-TACE group were significantly better than those for the non-PA-TACE group (P<0.0001, P<0.0001, respectively). After Cox regression analysis of OS or RFS, PA-TACE-related nomogram models were constructed. The C-index of the PA-TACE-related nomogram for OS and RFS was 0.72 and 0.73, respectively. Calibration curves revealed a good agreement between predictions and observations for the nomograms. Based on the nomogram-related risk stratification, Kaplan-Meier curves showed powerful discriminative ability. Conclusions: PA-TACE therapy improved the survival of HCC patients with PVTT undergoing hepatectomy. Accurate nomogram models were developed for predicting the individual survival and recurrence of these patients.
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Affiliation(s)
- Fuchen Liu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Xinggang Guo
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China.,Changhai Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Wei Dong
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Wenli Zhang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Shuxun Wei
- The First Department of General Surgery, Changzheng Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Shutong Zhang
- Department of Nephrology, First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Xiuli Zhu
- Department of Gastroenterology, Anhui Provincial Hospital, University of Science and Technology of China, Hefei, 230001, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
| | - Jinmin Zhang
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China
| | - Hui Liu
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Navy Medical University, Shanghai 200438, China
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Sparchez Z, Mocan T, Hagiu C, Kacso G, Zaharie T, Rusu I, Al Hajjar N, Leucuta DC, Sparchez M. Real-Time Contrast-Enhanced-Guided Biopsy Compared with Conventional Ultrasound-Guided Biopsy in the Diagnosis of Hepatic Tumors on a Background of Advanced Chronic Liver Disease: A Prospective, Randomized, Clinical Trial. ULTRASOUND IN MEDICINE & BIOLOGY 2019; 45:2915-2924. [PMID: 31447237 DOI: 10.1016/j.ultrasmedbio.2019.07.678] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 07/22/2019] [Accepted: 07/24/2019] [Indexed: 06/10/2023]
Abstract
We aimed to compare contrast-enhanced-guided liver biopsy (CEUSLB) and ultrasound-guided liver biopsy (USLB) in the diagnosis of focal liver lesions (FLLs) developed on a background of advanced chronic liver disease (ACLD). Between 2011 and 2019, patients diagnosed with liver tumors on a background of ACLD were evaluated for inclusion in the study. Patients were randomly assigned to the CEUSLB or USLB group. In total, 144 patients were randomly assigned to either CEUSLB (n = 79) or USLB (n = 65). Overall, in the CEUSLB group, the sensitivity was significantly better (94.74% vs. 74.6%, respectively; p = 0.001). Both the fragment length of the biopsy specimen and the single puncture success rate were statistically higher in the CEUSLB group (p = 0.022 and p = 0.0006, respectively). There was no difference in terms of major or minor complications (p = 0.682). CEUSLB is a feasible technique that increases the diagnostic sensitivity for liver tumors developed in ACLD.
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Affiliation(s)
- Zeno Sparchez
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Tudor Mocan
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
| | - Claudia Hagiu
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Gabriel Kacso
- Department of Medical Oncology and Radiotherapy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Toader Zaharie
- 3rd Pathology Department, Institute for Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Ioana Rusu
- 3rd Pathology Department, Institute for Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Nadim Al Hajjar
- 3rd Surgical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniel Corneliu Leucuta
- Medical Informatics and Biostatistics Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Mihaela Sparchez
- Iuliu Hatieganu University of Medicine and Pharmacy, 2nd Paediatric Clinic, Children's Hospital at Cluj-Napoca, Cluj-Napoca, Romania
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10
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Di Tommaso L, Spadaccini M, Donadon M, Personeni N, Elamin A, Aghemo A, Lleo A. Role of liver biopsy in hepatocellular carcinoma. World J Gastroenterol 2019; 25:6041-6052. [PMID: 31686761 PMCID: PMC6824282 DOI: 10.3748/wjg.v25.i40.6041] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/04/2019] [Accepted: 10/17/2019] [Indexed: 02/06/2023] Open
Abstract
The role of liver biopsy in the diagnosis of hepatocellular carcinoma (HCC) has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis. In fact, in the diagnostic algorithm for this tumor, histology is currently relegated to controversial cases. Furthermore, the risk of complications, such as tumor seeding and bleeding, as well as inadequate sampling have further limited the use of liver biopsy for HCC management. However, there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and, as the information content of the tissue sample increases, the advantages of liver biopsy might modify the current risk/benefit ratio. We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC. As the potentiality of precision medicine comes to the management of HCC, it will be crucial to have rapid pathways to define prognosis, and even treatment, by identifying the patients who could most benefit from target-driven therapies. All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.
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Affiliation(s)
- Luca Di Tommaso
- Pathology Unit, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Marco Spadaccini
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of General Surgery, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Nicola Personeni
- Division of Medical Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Abubaker Elamin
- Pathology Unit, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
| | - Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Italy
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11
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Fan W, Yang X, Huang F, Tong X, Zhu L, Wang S. Identification of CD206 as a potential biomarker of cancer stem-like cells and therapeutic agent in liver cancer. Oncol Lett 2019; 18:3218-3226. [PMID: 31452799 PMCID: PMC6704291 DOI: 10.3892/ol.2019.10673] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 06/13/2019] [Indexed: 12/11/2022] Open
Abstract
The mannose receptor (CD206) functions in endocytosis and phagocytosis, and plays an important role in immune homeostasis. Tumor-associated macrophages express high level of CD206 and are thought to contribute to cancer progression through tumor immunosuppression, metastasis and angiogenesis. However, the significance of CD206 in the pathology of liver cancer has not been investigated. The present study evaluated the clinical significance of CD206 in the progression and prognosis of liver cancer in pathological tissues from 327 patients. Increased CD206 expression was observed in liver cancer samples compared with healthy adjacent liver tissue (42.8 vs. 62.4%; P<0.05). CD206 expression was significantly associated with tumor size (P=0.009) and metastasis (P=0.041). The recurrence free survival rate of patients with CD206-positive liver cancer was significantly decreased compared with patients with CD206-negative liver cancer (P=0.003). A Cox regression model revealed that liver cancer survival was independently associated with tumor size, metastasis and α-fetoprotein value. The results further revealed that CD206 expression in cancer stem cell (CSC)-like cells was comparable to other internationally recognized biomarkers. Additionally, when CD206 expression was silenced in the liver cancer cell lines HepG2 and PLC/PRF/5 using a short hairpin RNA approach, migration and invasion of the cells significantly decreased compared with controls (P<0.01). CD206 expression in liver cancer significantly influences distant metastasis and spread, resulting in poor patient prognosis. Furthermore, CD206 may be a potential biomarker in CSC-like cells to predict the occurrence of liver cancer.
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Affiliation(s)
- Weimin Fan
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China.,Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Xue Yang
- Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Fang Huang
- Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Xiangmin Tong
- Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Lifen Zhu
- Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Shibing Wang
- Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
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12
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A Point-based Histologic Scoring System for Hepatocellular Carcinoma Can Stratify Risk of Posttransplant Tumor Recurrence. Am J Surg Pathol 2019; 42:855-865. [PMID: 29649017 DOI: 10.1097/pas.0000000000001053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eligibility for liver transplant is most commonly decided by measuring tumor size and number on radiographic imaging. However, this method often underestimates the extent of disease. Evaluation of tumor histology has been shown to improve risk stratification when compared with imaging-based transplant criteria, but the World Health Organization (WHO) guidelines for grading hepatocellular carcinoma (HCC) are imprecise and require subjective interpretation by the pathologist. We performed a retrospective analysis of 190 explanted livers containing HCC and correlated histologic features with posttransplant recurrence to formulate a three-tiered, point-based scoring system that categorizes tumors as having a low, intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score (RRAS) evaluates tumor architecture and specific cytologic features-nuclear pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing superior stratification of HCC recurrence risk compared with imaging criteria and grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the rate of recurrence after transplant was 0% among low-risk tumors (compared with 3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared with 15% of moderately differentiated tumors), and 54% among high-risk tumors (compared with 29% of poorly differentiated tumors). Receiver operating characteristic analysis shows significantly improved performance of RRAS criteria in predicting HCC recurrence compared with WHO grade (area under curve of 0.841 and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor histology offers superior prediction of recurrence risk following liver transplantation compared with radiographic criteria, and that the RRAS system better stratifies recurrence risk compared with HCC grading by WHO methodology.
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13
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Huang K, Dong Z, Cai H, Huang M, Peng Z, Xu L, Jia Y, Song C, Li ZP, Feng ST. Imaging biomarkers for well and moderate hepatocellular carcinoma: preoperative magnetic resonance image and histopathological correlation. BMC Cancer 2019; 19:364. [PMID: 30999947 PMCID: PMC6472074 DOI: 10.1186/s12885-019-5574-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 04/03/2019] [Indexed: 12/20/2022] Open
Abstract
Background Our aim of the study is to investigate the feasibility of preoperative prediction for hepatocellular carcinoma (HCC) histological grading using gadoxetic acid-enhanced magnetic resonance imaging (MRI). Methods This study included one hundred and fifty-six patients with solitary HCC. Preoperative gadoxetic acid-enhanced MRI findings were retrospectively analyzed. MRI qualitative features such as tumor size, margin, capsule status, signal homogeneity, intratumoral vessels, peritumoral enhancement during mid-arterial phase, peritumoral hypointensity during the hepatobiliary phase (HBP) were investigated. Apparent diffusion coefficients (ADCs), T1 reduction ratio of pre- and post-contrast enhanced images of the tumors were calculated. HCC histological grading in surgical specimens were confirmed by Edmonson’s criteria. Correlations between these MRI features and HCC histological grading were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the model. Results Univariate analysis showed that maximum tumor diameter (p = 0.004), tumor margin (p = 0.006), intratumoral vessels (p = 0.001) and peritumoral hypointensity during HBP (p = 0.000), were significantly correlated with HCC histological grading. There was no relationship between capsule, tumor signal, venous thrombosis, peritumoral enhancement during mid-arterial phase, ADC value, T1 reduction ratio, and HCC histological grading. Multivariate logistic regression analysis demonstrated that the maximum tumor diameter (p = 0.012, odds ratio = 1.002, 95% confidence interval: 1.007–1.046)) was an independent risk factor for high grade HCC. Conclusions Greater tumor size, a more irregular margin, presence of intratumoral vessels, and peritumoral hypointensity during HBP were indicators for high grade HCC. The maximum tumor diameter was an independent risk factor for high grade HCC. Electronic supplementary material The online version of this article (10.1186/s12885-019-5574-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kun Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.,Department of Radiology, Guizhou Provincial People's Hospital, No. 83 East, Zhongshan Road, Guiyang, 550002, Guizhou, China
| | - Zhi Dong
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Huasong Cai
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Mengqi Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Ling Xu
- Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia
| | - Yingmei Jia
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Chenyu Song
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.
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14
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Marasco G, Colecchia A, Colli A, Ravaioli F, Casazza G, Bacchi Reggiani ML, Cucchetti A, Cescon M, Festi D. Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection. J Hepatol 2019; 70:440-448. [PMID: 30389551 DOI: 10.1016/j.jhep.2018.10.022] [Citation(s) in RCA: 124] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 10/11/2018] [Accepted: 10/19/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. METHODS We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. RESULTS We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins <1 cm and being beyond the Milan criteria. HCC late recurrence at univariate analysis was associated with esophageal varices (hazard ratio [HR] 3.321, 95% CI 1.564-7.053), spleen length (HR 3.123, 95% CI 1.377-7.081), platelet/spleen length ratio if <909 (HR 2.170, 95% CI 1.026-4.587), LSM (HR 1.036, 95% CI 1.005-1.067), SSM (HR 1.046, 95% CI 1.020-1.073). HCC late recurrence at multivariate analysis was independently associated only with SSM (HR 1.046, CI 1.020-1.073). Late HCC recurrence-free survival was significantly different according to the SSM cut-off of 70 kPa (p = 0.0002). CONCLUSIONS SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. LAY SUMMARY The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy.
| | - Agostino Colli
- Department of Internal Medicine, A. Manzoni Hospital ASST Lecco, Lecco, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Giovanni Casazza
- Dipartimento di Scienze Biomediche e Cliniche "L. Sacco" - Universita' degli Studi di Milano, Milan, Italy
| | | | | | - Matteo Cescon
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, Italy
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15
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Chen X, Kutaiba N, Ngo B, Goodwin M. Outcome and safety of targeted liver biopsies for indeterminate lesions in patients with chronic liver disease: A single centre experience. J Med Imaging Radiat Oncol 2019; 63:190-196. [PMID: 30652433 DOI: 10.1111/1754-9485.12856] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 12/17/2018] [Indexed: 12/21/2022]
Abstract
INTRODUCTION To evaluate the histopathological and safety outcomes of indeterminate lesions in patients at high risk for developing hepatocellular carcinoma (HCC) who underwent ultrasound-guided biopsies. METHODS Ultrasound-guided targeted liver biopsies for indeterminate lesions performed in a 10-year period at our institution were reviewed retrospectively for lesion characteristics, biopsy techniques, histopathological results and post procedural complications. RESULTS A total of 172 biopsies were performed in 152 patients. Most common background liver disease included hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis. 65.1% had known cirrhosis at time of biopsy. HCC was the most common histopathological finding accounting for 55.8% of all biopsies, followed by cholangiocarcinoma, dysplastic nodule and metastasis. Rarer lesions including lymphoma, neuroendocrine tumour and angiomyolipoma were also encountered. No mortality, clinically significant bleeding or tumour seeding was detected. CONCLUSIONS Ultrasound-guided liver biopsies of indeterminate lesions in patients at high risk of HCC yield important histopathological findings, important for management options including the provision of curative treatments and assisting future novel therapies such as immunotherapy and targeted therapies. The low complication rates confirm its safety and the procedure should not be avoided for fear of complications.
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Affiliation(s)
- Xiao Chen
- Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Numan Kutaiba
- Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Brian Ngo
- Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia
| | - Mark Goodwin
- Department of Radiology, Austin Hospital, Melbourne, Victoria, Australia.,Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
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16
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Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria. Transplantation 2018; 102:648-655. [PMID: 29319629 DOI: 10.1097/tp.0000000000002056] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. METHODS Patients who underwent orthotopic liver transplantation for HCC after preoperative MRI were identified in a prospectively collected institutional database (January 2003 to December 2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were used to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. RESULTS Of 318 patients with HCC meeting Milan criteria by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0 months, P = 0.005), and did not vary between patients exceeding criteria due to tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than 3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95% confidence interval, 1.37-5.79; P = 0.005). CONCLUSIONS Underestimating HCC burden before liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing alpha fetal protein before transplantation may benefit from more frequent testing or novel neoadjuvant therapies.
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17
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Zheng J, Shen S, Jiang L, Yan L, Yang J, Li B, Wen T, Wang W, Xu M. Outcomes of anterior approach major hepatectomy with diaphragmatic resection for single huge right lobe HCC with diaphragmatic invasion. Medicine (Baltimore) 2018; 97:e12194. [PMID: 30200125 PMCID: PMC6133608 DOI: 10.1097/md.0000000000012194] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 08/09/2018] [Indexed: 02/06/2023] Open
Abstract
The outcomes following anterior approach (AA) hepatectomy in huge hepatocellular carcinoma (HCC) patients with diaphragmatic invasion (DI) remain unclear. This study compared the outcomes of single huge right HCC patients with and without DI after AA hepatectomy. A total of 203 consecutive patients with single huge right lobe HCC who underwent AA major hepatectomy were included. They were divided into group PDI (n = 53) and group ADI (n = 150) according to the presence or the absence of DI. Their short- and long-term outcomes were compared, and a subgroup analysis was performed. There were no significant differences regarding postoperative complications and 90-day mortality between the 2 groups. The overall survival (OS) and recurrence-free survival (RFS) rates were similar between the 2 groups. The subgroup analysis also showed that patients with tumor resection en bloc with part of the diaphragm had similar OS and RFS rates as those who underwent diaphragmatic resection after hepatectomy. Tumor diameter ≥ 15 cm, serum AFP level ≥ 400 ng/mL, and tumor grade of G4 and microvascular invasion are independent predictors of poor prognosis. For the single huge right lobe HCC patients with DI, AA major hepatectomy combined with diaphragmatic resection could offer similar OS and RFS as those without diaphragmatic invasion.
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18
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Sparchez Z, Mocan T. Contemporary role of liver biopsy in hepatocellular carcinoma. World J Hepatol 2018; 10:452-461. [PMID: 30079131 PMCID: PMC6068845 DOI: 10.4254/wjh.v10.i7.452] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/29/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
A correct diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patients with focal liver lesions is one of the most important issues nowadays. Probably one of the oldest debates in the hepatology community is whether to perform liver biopsy (LB) in all cirrhotic patients with focal liver lesions. We now face a time when oncology is moving towards personalized medicine. According to the current European Association for the study of Liver diseases HCC guidelines, LB has only a minor role in the management of HCC. However, the current recommendations were made more than five years ago. As time has passed, the development of high-throughput molecular technologies has helped reveal the main molecular mechanism involved in HCC development and progression. Several subtypes of HCC, with both molecular and histological characterization, have been described. Importantly, some of these subtypes have prognostic impact. In the context of personalized treatment, the role of LB will be carefully reconsidered. Until then, it is mandatory to know the various techniques of LB, their performances, complications and limitations. The balance of risk and benefit defines many of the decisions that we make as providers of medical care. In this review, we discuss not only the risks associated with LB, but also the benefits of biopsy in various clinical scenarios. Not long from now, the role of LB will be reconsidered. It is possible that we will go back in time and once again use biopsy for HCC diagnosis. Then again, we may move back to the future to try to improve the use of liquid biopsy in the follow-up of HCC patients after various treatment modalities.
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Affiliation(s)
- Zeno Sparchez
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
| | - Tudor Mocan
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
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Russo FP, Imondi A, Lynch EN, Farinati F. When and how should we perform a biopsy for HCC in patients with liver cirrhosis in 2018? A review. Dig Liver Dis 2018; 50:640-646. [PMID: 29636240 DOI: 10.1016/j.dld.2018.03.014] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 03/07/2018] [Accepted: 03/09/2018] [Indexed: 12/11/2022]
Abstract
The role of liver biopsy in the diagnosis of hepatocellular carcinoma (HCC) has changed over time. The diagnostic algorithm for this tumor is nowadays mainly based on radiological imaging, relegating histology to controversial cases, in which imaging techniques cannot establish a clear-cut diagnosis. This most commonly happens in small lesions, where biopsies frequently become mandatory, or in larger hypovascularized lesions. In this case however, the histological examination may not be reliable enough to grade the lesion, as different cell clones, deriving from sequential mutations, can originate heterogeneous cell populations. The risk of complications of liver biopsy, such as tumor seeding and intra-abdominal bleeding, needs to be reconsidered in light of new scientific evidence and of the technical improvements that have been introduced. Furthermore, increasing knowledge of the immunohistochemical and molecular characteristics of hepatocellular carcinoma opens a new scenario in which biopsy may play a decisive role in defining prognosis, and even treatment, by identifying the patient populations who could most benefit from target-driven hepatocellular carcinoma treatments, and therefore improving the success rate of experimental therapies. All the above reasons suggest that, overall, the role of liver biopsy in the management of HCC needs a reappraisal.
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Affiliation(s)
- Francesco Paolo Russo
- Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, Padua, Italy
| | - Angela Imondi
- Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, Padua, Italy
| | - Erica Nicola Lynch
- Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, Padua, Italy
| | - Fabio Farinati
- Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, Padua, Italy.
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20
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Santambrogio R, Cigala C, Barabino M, Maggioni M, Scifo G, Bruno S, Bertolini E, Opocher E, Bulfamante G. Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology. Liver Int 2018; 38:312-320. [PMID: 28732141 DOI: 10.1111/liv.13524] [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: 05/26/2017] [Accepted: 07/13/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. METHODS All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. RESULTS A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. CONCLUSIONS In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma.
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Affiliation(s)
- Roberto Santambrogio
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Claudia Cigala
- U.O.C. Anatomia Patologica, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Matteo Barabino
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Marco Maggioni
- U.O.C. Anatomia Patologica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università di Milano, Milano, Italy
| | - Giovanna Scifo
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Savino Bruno
- Humanitas University Medicine and Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Emanuela Bertolini
- Cattedra di Medicina Interna, Azienda Ospedaliera San Paolo - Dipartimento di Medicina, Chirurgia ed Odontoiatria, Università degli Studi di Milano, Milan, Italy
| | - Enrico Opocher
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Gaetano Bulfamante
- U.O.C. Anatomia Patologica, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
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21
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Wang J, Shen JL. Spectral CT in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma: A retrospective study. Medicine (Baltimore) 2017; 96:e9236. [PMID: 29384909 PMCID: PMC6393018 DOI: 10.1097/md.0000000000009236] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
This study aimed to investigate the value of computed tomographic (CT) spectral imaging in evaluating the effect of transarterial chemoembolization (TACE).The records of 67 patients with hepatocellular carcinoma (HCC) who had undergone dynamic spectral CT before treatment were selected for the study. Iodine concentrations pretreatment in liver parenchyma, the HCC lesion(s), portal vein, and aorta were measured from the decomposition images. The normalized iodine concentrations (NIC) were calculated. All of them underwent plain scan or contrast-enhanced CT post-treatment (approximately 4-6 weeks after TACE).The values of arterial phase normalized iodine concentrations (AP NIC) before TACE correlated with the grades of lipiodol deposition in tumors (r = 0.76, P < .001). However, there was no relationship between normalized iodine concentrations in the portal venous phase (PVP NIC) before TACE and the grade of lipiodol deposition (r = 0.17, P = .17). Values of AP NIC in residual tumors pre-TACE were significantly lower than those in partial lesions with deposition of iodized oil. The threshold AP NIC of 0.18 yielded an AUC of 0.895, 83.33% sensitivity, 81.03% specificity, 83.33% positive predictive value (PPV), and 82.76% negative predictive value, respectively. The survival probability in patients with AP NIC values pre-TACE ≥ 0.18 was higher than those whose AP NIC values pre-TACE were < 0.18 (P = .028).Spectral CT with quantitative analysis of AP NIC may help to evaluate the utility and predict the therapeutic effect of TACE. Values of AP NIC had high sensitivity and specificity for differentiating partial tumors with lipiodol deposition from those without lipiodol deposition.
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Szpakowski JL, Drasin TE, Lyon LL. Rate of seeding with biopsies and ablations of hepatocellular carcinoma: A retrospective cohort study. Hepatol Commun 2017; 1:841-851. [PMID: 29404497 PMCID: PMC5721456 DOI: 10.1002/hep4.1089] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 07/18/2017] [Accepted: 07/29/2017] [Indexed: 12/13/2022] Open
Abstract
Biopsies of liver masses that prove to be hepatocellular carcinomas (HCCs) are associated with a risk of seeding the abdominal or chest wall with tumor cells. The reported frequency of seeding varies greatly in the literature. We performed a retrospective cohort study in a large integrated health care system to examine rates of seeding in patients with HCC who had targeted liver biopsies, ablations, or both performed by community radiologists. We reviewed pathology and radiology records to determine the occurrence of wall seeding, defined as a chest or abdominal wall lesion along a definite or probable needle tract. A total of 1,015 patients had targeted liver biopsies (795), ablations (72), or both (148). Multiple procedures were done in 284 patients (28%). Six cases of seeding were identified. The rate of wall seeding was 2/795 patients (0.13%; 95% confidence interval [CI], 0.00%-0.60%) if only biopsies were done versus 4/220 (1.82%; 95% CI, 0.05%-3.58%) if ablations were performed (P = 0.01). The rate was 0/72 (0.00%; 95% CI, 0.00%-0.04%) with ablations alone and 4/148 (2.70%; 95% CI, 0.74%-6.78%) if both procedures were done (P = 0.31). Of those with 1 year follow-up (n = 441), the rate of seeding was 2/269 (0.74%; 95% CI, 0.00%-1.77%) if biopsies alone were done and 4/172 (2.33%; 95% CI, 0.07%-4.58%) if ablations were done. In none of the cases was the seeding a proximate cause of death. Conclusion: Biopsies of liver masses are associated with a low rate of wall seeding when performed in a community setting and when they are the sole procedures. Ablations may have a higher rate of seeding, particularly if done with biopsies, but are still rare. (Hepatology Communications 2017;1:841-851).
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Affiliation(s)
| | - Todd E Drasin
- Radiology Department Kaiser Permanente Walnut Creek CA
| | - Liisa L Lyon
- Division of Research Kaiser Permanente Oakland CA
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23
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Wang F, Li J, Li R, Pan G, Bai M, Huang Q. Angelicin inhibits liver cancer growth in vitro and in vivo. Mol Med Rep 2017; 16:5441-5449. [PMID: 28849216 PMCID: PMC5647089 DOI: 10.3892/mmr.2017.7219] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 06/26/2017] [Indexed: 01/12/2023] Open
Abstract
Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose‑ and time‑dependent manner. Furthermore, in HepG2 and Huh‑7 cells, angelicin‑induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase/RAC‑α serine/threonine-protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer.
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Affiliation(s)
- Fengliang Wang
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
| | - Jun Li
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
| | - Rong Li
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
| | - Guohua Pan
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
| | - Mingxia Bai
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
| | - Qiang Huang
- Department of Hepatobiliary Surgery, Affiliated Minda Hospital of Hubei Institute for Nationalities, Enshi, Hubei 445000, P.R. China
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24
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The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma. Sci Rep 2017; 7:3089. [PMID: 28596599 PMCID: PMC5465066 DOI: 10.1038/s41598-017-03407-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 04/27/2017] [Indexed: 01/05/2023] Open
Abstract
The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently induces the down-regulation of miR-125a expression in hepatocellular carcinoma (HCC) cells and tumors. Furthermore, we demonstrate that miR-125a could decrease the production of lactate, the uptake of glucose, and the levels of ATP and reactive oxygen species (ROS) in HCC cells. We investigated the molecular mechanism through which miR-125a inhibits HCC glycolysis and identified hexokinase II (HK2) as a direct target gene of miR-125a. Finally, we revealed that the miR-125a/HK2 axis is functionally important for regulating glycolysis of HCC cell and progression of cancer in vitro and in vivo. In summary, our findings demonstrate for the first time that hypoxia-down-regulated miR-125a regulated HCC glycolysis and carcinogenesis by targeting hexokinase HK2, a key glycolytic enzyme for the Warburg effect, and add a new dimension to hypoxia-mediated regulation of cancer metabolism.
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25
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Biolato M, Marrone G, Miele L, Gasbarrini A, Grieco A. Liver transplantation for intermediate hepatocellular carcinoma: An adaptive approach. World J Gastroenterol 2017; 23:3195-3204. [PMID: 28566879 PMCID: PMC5434425 DOI: 10.3748/wjg.v23.i18.3195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 03/12/2017] [Accepted: 04/12/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness (α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented “adaptive approach”, in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria.
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26
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Zhang W, Tan Y, Jiang L, Yan L, Li B, Wen T, Yang J. Liver resection associated with better outcomes for single large hepatocellular carcinoma located in the same section. Medicine (Baltimore) 2017; 96:e6246. [PMID: 28272222 PMCID: PMC5348170 DOI: 10.1097/md.0000000000006246] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The influence of the anatomical location of single large hepatocellular carcinoma (HCC) on outcomes following hepatic resection (HR) is still unclear. This study examined the role of anatomical location profiles as prognostic markers for patients with single large HCC undergoing HR.A total of 374 consecutive patients with single large HCC undergoing HR between January 2009 and July 2013 were included. They were divided into group same section (SS) group (n = 171) and different sections (DS) group (n = 203) according to their tumor's anatomical location. Short- and long-term outcomes were compared between the two groups.More patients in group DS had intraoperative blood loss of >1000 mL and needed intraoperative blood transfusion than those in group SS. There were no significant differences regarding postoperative complications and 30-and 90-day mortality between the two groups. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher in group SS than group DS. The subgroup analysis showed that tumor in the same section was associated with better prognosis than those in different sections for both patients with tumor of ≤8 cm and of > 8 cm. Multivariate analysis revealed that age <60 years, portal hypertension, alpha-fetoprotein ≥400 ng/mL, tumor in different sections, microvascular invasion and poorly differentiated tumor are independent predictors of poor prognosis in patient with single large HCC.For patients with single large HCC, a tumor located in the same section may lead to better long-term survival and lower tumor recurrence rates than those in different sections following HR.
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Affiliation(s)
- Wei Zhang
- Department of Liver Surgery, Liver Transplantation Center
| | - Yongqiong Tan
- Center for Operating Room and Anesthesia, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Department of Liver Surgery, Liver Transplantation Center
| | - Lunan Yan
- Department of Liver Surgery, Liver Transplantation Center
| | - Bo Li
- Department of Liver Surgery, Liver Transplantation Center
| | - Tianfu Wen
- Department of Liver Surgery, Liver Transplantation Center
| | - Jiayin Yang
- Department of Liver Surgery, Liver Transplantation Center
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27
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28
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Jin F, Wang Y, Li M, Zhu Y, Liang H, Wang C, Wang F, Zhang CY, Zen K, Li L. MiR-26 enhances chemosensitivity and promotes apoptosis of hepatocellular carcinoma cells through inhibiting autophagy. Cell Death Dis 2017; 8:e2540. [PMID: 28079894 PMCID: PMC5386370 DOI: 10.1038/cddis.2016.461] [Citation(s) in RCA: 170] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 11/09/2016] [Accepted: 12/07/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) generally possesses a high resistance to chemotherapy. Given that autophagy is an important factor promoting tumor chemoresistance and HCC express low level of miR-26, we aim to investigate the functional role of miR-26 in autophagy-mediated chemoresistance of HCC. We found that chemotherapeutic drug doxorubicin (Dox) induced autophagy but decreased the level of miR-26a/b in HCC cells. Activating autophagy using rapamycin can directly downregulate the level of miR-26a/b in HCC cells. In turn, restoring the expression of miR-26a/b inhibited autophagy induced by Dox and promoted apoptosis in HCC cells. Further mechanistic study identified that miR-26a and miR-26b target ULK1, a critical initiator of autophagy, at post-transcriptional level. Results from 30 cases of patients with HCC also showed that tumor cellular levels of miR-26a and miR-26b are significantly downregulated as compared with the corresponding control tissues and negatively correlated with the protein level of ULK1 but are not correlated to the mRNA level of ULK1. Gain- and loss-of-function assay confirmed that miR-26a/b inhibited autophagic flux at the initial stage through targeting ULK1. Overexpression of miR-26a/b enhanced the sensitivity of HCC cells to Dox and promoted apoptosis via inhibiting autophagy in vitro. Using xenograft models in nude mice, we confirmed that miR-26a/b, via inhibiting autophagy, promoted apoptosis and sensitized hepatomas to Dox treatment in vivo. Our findings demonstrate for the first time that miR-26a/b can promote apoptosis and sensitize HCC to chemotherapy via suppressing the expression of autophagy initiator ULK1, and provide the reduction of miR-26a/b in HCC as a novel mechanism of tumor chemoresistance.
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Affiliation(s)
- Fangfang Jin
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Yanbo Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Mingzhen Li
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Yanan Zhu
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Hongwei Liang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Chen Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Feng Wang
- Affiliated Gulou Hospital, Medical College of Nanjing University, Nanjing, Jiangsu, China
| | - Chen-Yu Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Ke Zen
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
| | - Limin Li
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, Jiangsu, China
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29
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Jian J, Zhang W, Yang H, Zhao X, Xuan R, Li D, Hu C. Phase-contrast CT: Qualitative and Quantitative Evaluation of Capillarized Sinusoids and Trabecular Structure in Human Hepatocellular Carcinoma Tissues. Acad Radiol 2017; 24:67-75. [PMID: 27818006 DOI: 10.1016/j.acra.2016.08.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 08/14/2016] [Accepted: 08/25/2016] [Indexed: 12/17/2022]
Abstract
RATIONALE AND OBJECTIVES Capillarization of sinusoids and change of trabecular thickness are the main histologic features in hepatocellular carcinoma (HCC). Of particular interest are the three-dimensional (3D) visualization and quantitative evaluation of such alterations in the HCC progression. X-ray phase-contrast computed tomography (PCCT) is an emerging imaging method that provides excellent image contrast for soft tissues. This study aimed to explore the potential of in-line PCCT in microstructure imaging of capillarized sinusoids and trabecular structure in human HCC tissues and to quantitatively evaluate the alterations of those fine structures during the development of HCC. MATERIALS AND METHODS This project was designed as an ex vivo experimental study. The study was approved by the institutional review board, and informed consent was obtained from the patients. Eight human resected HCC tissue samples were imaged using in-line PCCT. After histologic processing, PCCT images and histopathologic data were matched. Fine structures in HCC tissues were revealed. Quantitative analyses of capillarized sinusoids (ie, percentage of sinusoidal area [PSA], sinusoidal volume) and trabecular structure (ie, trabecular thickness, surface-area-to-volume ratio [SA/V]) in low-grade (well or moderately differentiated) and high-grade (poorly differentiated) HCC groups were performed. RESULTS Using PCCT, the alterations of capillarized sinusoids and trabecular structure were clearly observed in 3D geometry, which was confirmed by the corresponding histologic sections. The 3D qualitative analyses of sinusoids in the high-grade HCC group were significantly different (P < 0.05) in PSA (7.8 ± 2.5%) and sinusoidal volume (2.9 ± 0.6 × 107 µm3) from those in the low-grade HCC group (PSA, 12.9 ± 2.2%; sinusoidal volume, 2.4 ± 0.3 × 107 µm3). Moreover, the 3D quantitative evaluation of the trabecular structure in the high-grade HCC group showed a significant change (P < 0.05) in the trabecular thickness (87.8 ± 15.6 µm) and SA/V (2.2 ± 1.3 × 103 µm-1) compared to the low-grade HCC group (trabecular thickness, 75.9 ± 7.1 µm; SA/V, 7.5 ± 1.3 × 103 µm-1). CONCLUSIONS This study provides insights into the 3D alterations of microstructures such as capillarized sinusoids and the trabecular structure at a micrometer level, which might allow for an improved understanding of the development of HCC.
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30
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Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A, Ghanekar A, Cleary SP, Lilly L, Cattral MS, Marquez M, Selzner M, Renner E, Selzner N, McGilvray ID, Greig PD, Grant DR. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study. Hepatology 2016; 64:2077-2088. [PMID: 27178646 DOI: 10.1002/hep.28643] [Citation(s) in RCA: 250] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 04/25/2016] [Accepted: 05/11/2016] [Indexed: 12/11/2022]
Abstract
UNLABELLED The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. CONCLUSION Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).
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Affiliation(s)
- Gonzalo Sapisochin
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Nicolas Goldaracena
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Jerome M Laurence
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Martin Dib
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Andrew Barbas
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Anand Ghanekar
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Sean P Cleary
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Les Lilly
- Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Mark S Cattral
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Max Marquez
- Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Markus Selzner
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Eberhard Renner
- Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Nazia Selzner
- Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Ian D McGilvray
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Paul D Greig
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - David R Grant
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.,Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada
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31
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Schlageter M, Quagliata L, Matter M, Perrina V, Tornillo L, Terracciano L. Clinicopathological Features and Metastatic Pattern of Hepatocellular Carcinoma: An Autopsy Study of 398 Patients. Pathobiology 2016; 83:301-7. [DOI: 10.1159/000446245] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 04/13/2016] [Indexed: 11/19/2022] Open
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32
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Xu X, Lu D, Ling Q, Wei X, Wu J, Zhou L, Yan S, Wu L, Geng L, Ke Q, Gao F, Tu Z, Wang W, Zhang M, Shen Y, Xie H, Jiang W, Wang H, Zheng S. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut 2016; 65:1035-41. [PMID: 25804634 PMCID: PMC4893115 DOI: 10.1136/gutjnl-2014-308513] [Citation(s) in RCA: 180] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 03/04/2015] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Liver transplantation is an optimal radical therapy for selected patients with hepatocellular carcinoma. The stringent organ allocation system driven by the Milan criteria has been challenged by alternative sets of expanded criteria. Careful analysis is needed to prove that the Milan criteria can be expanded safely and effectively. DESIGN This study collectively reviewed 6012 patients of hepatocellular carcinoma from the China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised expansion with acceptable outcomes beyond the Milan criteria. RESULTS Compared with the Milan criteria, Valencia, University of California, San Francisco, University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%, 19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded criteria were comparable to that of the Milan criteria. The analysis of net reclassification improvement and area under the receiver operating characteristic curves showed an excellent efficiency in recurrence prediction for the expanded criteria compared with the Milan criteria. In patients exceeding Milan but fulfilling the Hangzhou criteria (N=1352), α-fetoprotein (AFP) >100 ng/mL and tumour burden>8 cm were the only two independent prognostic factors (p<0.001). Accordingly, the Hangzhou criteria were stratified as type A (tumour burden ≤8 cm, or tumour burden >8 cm but AFP≤100 ng/mL) and type B (tumour burden >8 cm but AFP between 100 and 400 ng/mL). Type A showed significantly higher 5-year tumour-free survival rates compared with type B (p<0.001). CONCLUSIONS The Milan criteria can be expanded safely and effectively. The prognostic stratification system based on the Hangzhou criteria serves as a hierarchy of transplant candidates for hepatocellular carcinoma.
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Affiliation(s)
- Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Di Lu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuyong Wei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lin Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liming Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lei Geng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qinghong Ke
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Gao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhenhua Tu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenshi Jiang
- China Liver Transplant Registry, Shenzhen, China
| | - Haibo Wang
- China Liver Transplant Registry, Shenzhen, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
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Ferrer-Fàbrega J, Forner A, Liccioni A, Miquel R, Molina V, Navasa M, Fondevila C, García-Valdecasas JC, Bruix J, Fuster J. Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection. Hepatology 2016; 63:839-49. [PMID: 26567038 DOI: 10.1002/hep.28339] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 11/09/2015] [Indexed: 12/19/2022]
Abstract
UNLABELLED A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites; ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. From 1995 to 2012, 164 patients with hepatocellular carcinoma underwent resection. Eighty-five patients were potential candidates for liver transplantation and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed, and salvage liver transplantation was considered upon development of tumor recurrence/liver function impairment. Thirty-seven patients were at high risk and 48 at low risk of recurrence at pathology. Twenty-three out of 37 high-risk patients recurred during follow-up, but in nine of them the tumor burden extent contraindicated liver transplantation. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median posttransplant follow-up of 50.9 months, hepatocellular carcinoma had recurred in two patients and five patients had died, the 5-year survival being 82.4%. Twenty-six of the 48 low-risk patients developed recurrence, and 11 of them were transplanted. After a median posttransplant follow-up of 59 months, two patients developed recurrence and five died, their 5-year survival being 81.8%. CONCLUSION Enlistment of patients at high risk of HCC recurrence after resection but before recurrence development seems a valid strategy and is associated with excellent long-term outcome; as early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment; however, once included on the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence.
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Affiliation(s)
- Joana Ferrer-Fàbrega
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, University of Barcelona, Barcelona, Spain.,Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Alexandre Liccioni
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.,Department of Pathology, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain
| | - Víctor Molina
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.,Liver Transplantation Unit, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Constantino Fondevila
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Juan Carlos García-Valdecasas
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, University of Barcelona, Barcelona, Spain.,Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
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Severity of cirrhosis should determine the operative modality for patients with early hepatocellular carcinoma and compensated liver function. Surgery 2016; 159:621-31. [PMID: 26453137 DOI: 10.1016/j.surg.2015.09.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 08/18/2015] [Accepted: 09/02/2015] [Indexed: 01/08/2023]
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Wang L, Wang J, Zhang X, Li J, Wei X, Cheng J, Ling Q, Xie H, Zhou L, Xu X, Zheng S. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma. PLoS One 2015; 10:e0144216. [PMID: 26658912 PMCID: PMC4682812 DOI: 10.1371/journal.pone.0144216] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 10/19/2015] [Indexed: 12/20/2022] Open
Abstract
Background Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate. Objective To identify the influence of number of biopsies on NCB diagnostic accuracy. Methods 153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis. Results Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5cm. For HCC >5≤8cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively. Conclusions The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5cm.
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Affiliation(s)
- Lijun Wang
- Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianguo Wang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Xuanyu Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Jie Li
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Xuyong Wei
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Jun Cheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Haiyang Xie
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lin Zhou
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
- * E-mail: (SZ); (XX)
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
- * E-mail: (SZ); (XX)
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Osório FMF, Vidigal PVT, Ferrari TCA, Lima AS, Lauar GM, Couto CA. Histologic Grade and Mitotic Index as Predictors of Microvascular Invasion in Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2015. [PMID: 26221994 DOI: 10.6002/ect.2015.0045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Microvascular invasion is a well-known risk factor for hepatocellular carcinoma recurrence and mortality after hepatic resection and liver transplant. We sought to determine the clinico-pathological predictive factors associated with microvascular invasion. MATERIALS AND METHODS We studied all patients who had undergone liver transplant because of hepatocellular carcinoma between July 2001 and December 2010 at our institution. Laboratory tests, clinical, and demographic data were obtained. Histopathological hematoxylin and eosin specimens were performed by a single liver pathologist. RESULTS During the study, 107 patients had LT because of HCC and they were selected for this investigation: 76 were men (71%) and 31 women (29%) (mean age, 56.8 ± 8.7 y). It was not possible to retrieve histologic samples from 5 patients; therefore, the final studied analysis was 102 individuals. Tumor recurrence rate was 12.9%. One-, three- and five-year overall survivals were 75.0%, 71.4%, and 67.5%. Mitotic index, histologic grade, tumor architecture, alpha-fetoprotein, and tumor fibrosis were associated with microvascular invasion on univariate analysis. Significant independent predictors of microvascular invasion on logistic regression analysis were histologic grade and mitotic index (P < .001; odds ratio, 3.16; 95% confidence interval, 1.525-4.156, and P = .046; odds ratio, 2.56; 95% confidence interval, 1.061-6.451). CONCLUSIONS Mitotic index and histologic grade are significant predictors of microvascular invasion. No other risk factor was identified in the logistic regression. As both pathological characteristics may be assessed by liver biopsy, these results highlight the importance of discussing pretransplant liver biopsy to access prognosis and define treatment modalities in the setting of liver transplant.
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Affiliation(s)
- Fernanda Maria Farage Osório
- Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte; and the Alfa Gastroenterology Institute, University Hospital, Federal University of Minas Gerais, Belo Horizonte
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Abstract
The increasing incidence of hepatocellular carcinoma (HCC) has led to the need to identify patients at risk for HCC so that a program of screening can be undertaken. Screening for HCC has led to earlier diagnosis of tumors and thus has aided in initiating optimal medical treatment earlier in the disease course. Advances in radiological techniques and the identification of more accurate serum tests to diagnose HCC continue to be important areas of study and exploration. In particular, there have been efforts to develop new tumor markers to aid in the diagnosis of HCC and guide therapy of tumors.
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Affiliation(s)
- Heather N Simpson
- The University of Alabama School of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Boshell Diabetes Building, 1808 7th Avenue South, Birmingham, AL 35233, USA
| | - Brendan M McGuire
- The University of Alabama School of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Boshell Diabetes Building, 1808 7th Avenue South, Birmingham, AL 35233, USA.
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Molla N, AlMenieir N, Simoneau E, Aljiffry M, Valenti D, Metrakos P, Boucher LM, Hassanain M. The role of interventional radiology in the management of hepatocellular carcinoma. ACTA ACUST UNITED AC 2014; 21:e480-92. [PMID: 24940108 DOI: 10.3747/co.21.1829] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications. METHODS A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review. RESULTS Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities-transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)-tace is the method of choice in Child-Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis. CONCLUSIONS The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.
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Affiliation(s)
- N Molla
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia. ; Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - N AlMenieir
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia
| | - E Simoneau
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC
| | - M Aljiffry
- Department of Surgery, King Abdulaziz University, Jeddah, Saudi Arabia
| | - D Valenti
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - P Metrakos
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - L M Boucher
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - M Hassanain
- Section of Hepatopancreatobiliary and Transplant Surgery, McGill University Health Centre, Montreal, QC. ; Department of Surgery, King Saud University, Riyadh, Saudi Arabia
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Colecchia A, Schiumerini R, Cucchetti A, Cescon M, Taddia M, Marasco G, Festi D. Prognostic factors for hepatocellular carcinoma recurrence. World J Gastroenterol 2014; 20:5935-5950. [PMID: 24876717 PMCID: PMC4033434 DOI: 10.3748/wjg.v20.i20.5935] [Citation(s) in RCA: 131] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/14/2013] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.
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Méndez-Sánchez N, Ridruejo E, Alves de Mattos A, Chávez-Tapia NC, Zapata R, Paraná R, Mastai R, Strauss E, Guevara-Casallas LG, Daruich J, Gadano A, Parise ER, Uribe M, Aguilar-Olivos NE, Dagher L, Ferraz-Neto BH, Valdés-Sánchez M, Sánchez-Avila JF. Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma. Ann Hepatol 2014. [PMID: 24998696 DOI: 10.1016/s1665-2681(19)30919-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.
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Affiliation(s)
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC". Ciudad Autónoma de Buenos Aires, Argentina; Hepatology and Liver Transplant Unit. Hospital Universitario Austral, Pilar, Argentina
| | | | | | - Rodrigo Zapata
- Hepatology and Liver Transplantation Unit. University of Chile School of Medicine, German Clinic. Santiago, Chile
| | - Raymundo Paraná
- Associate Professor of School of Medicine - Federal University of Bahia Head of the Gastro-Hepatologist Unit of the University Bahia University Hospital
| | - Ricardo Mastai
- Transplantation Unit. German Hospital.Buenos Aires, Argentina
| | - Edna Strauss
- Clinical hepatologist of Hospital do Coraçao - São Paulo - Brazil. Professor of the Post Graduate Course in the Department of Pathology at the School of Medicine, University of São Paulo
| | | | - Jorge Daruich
- Hepatology Department, Clinical Hospital San Martín. University of Buenos Aires Buenos Aires, Argentina
| | - Adrian Gadano
- Section of Hepatology, Italian Hospital of Buenos Aires. Buenos Aires, Argentina
| | - Edison Roberto Parise
- Professor Associado da Disciplina de Gastroenterologia da Universidade Federal de São Paulo, Presidente Eleito da Sociedade Brasileira de Hepatologia
| | - Misael Uribe
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Nancy E Aguilar-Olivos
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Lucy Dagher
- Consultant Hepatologist. Metropolitan Policlinic- Caracas- Venezuela
| | - Ben-Hur Ferraz-Neto
- Director of Liver Institute - Beneficencia Portuguesa de São Paulo. Chief of Liver Transplantation Team
| | - Martha Valdés-Sánchez
- Department of Pediatric Oncology National Medical Center "Siglo XXI". Mexico City, Mexico
| | - Juan F Sánchez-Avila
- Hepatology and Liver Transplantation Department National Institute of Nutrition and Medical Sciences "Salvador Zubirán" Mexico City, Mexico
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Saito Y, Matsuzaki Y, Honda A, Iwamoto J, Ikegami T, Chiba T, Sugahara S, Okumura T, Tsujii H, Doy M, Tokuuye K. Post-therapeutic needle biopsy in patients with hepatocellular carcinoma is a useful tool to evaluate response to proton irradiation. Hepatol Res 2014; 44:403-9. [PMID: 23607877 DOI: 10.1111/hepr.12133] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 04/06/2013] [Accepted: 04/08/2013] [Indexed: 12/11/2022]
Abstract
AIM Proton beam therapy is safe and more effective than conventional radiation therapy for the local control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by imaging is not accurate during the early post-irradiation period. Therefore, we examined whether the histopathological study of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response. METHODS Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound-guided percutaneous fine-needle aspiration from the center of the tumor before, 3 weeks after and 1 year post-proton therapy. The specimens were examined after staining with hematoxylin-eosin (HE) and a MIB-1 antibody. RESULTS MIB-1 labeling indices (LI) before treatment were 13.0 ± 8.5% (mean ± SD; range, 0.6-27.0), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% (range, 0.6-8.9) (P < 0.05). Although the tumor size was reduced, we did not observe a reduction in tumor blood flow by dynamic computed tomography or degenerative changes by HE. All lesions that displayed reduced MIB-1 LI at 3 weeks post-proton treatment were ultimately diagnosed as complete response at 1 year after treatment. In contrast, one case with increased MIB-1 LI at 3 weeks had significant tumor size progression at 1 year post-treatment. CONCLUSION The percutaneous fine-needle aspiration biopsy of HCC is a safe and useful tool that can be used to evaluate the response to proton irradiation. In particular, MIB-1 LI may provide additional information to assess the therapeutic response of HCC during the early post-irradiated period.
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Affiliation(s)
- Yoshifumi Saito
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Yasushi Matsuzaki
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Akira Honda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Junichi Iwamoto
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Toshiya Chiba
- Department of Gastroenterology, Ushiku Aiwa General Hospital, Ushiku, Japan
| | - Shinji Sugahara
- Department of Radiology, Tokyo Medical University Ibaraki Medical Center, Ami, Japan
| | - Toshiyuki Okumura
- Department of Radiation Oncology, Tsukuba University, Tsukuba, Japan
| | - Hirohiko Tsujii
- Research Center for Charged Particle Therapy, National Institute of Radiological Science, Chiba, Japan
| | - Mikio Doy
- Department of Social Health and Welfare, Ibaraki Prefectural Government, Mito, Japan
| | - Koichi Tokuuye
- Department of Radiology, Tokyo Medical University, Tokyo, Japan
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Brimacombe CL, Wilson GK, Hübscher SG, McKeating JA, Farquhar MJ. A role for CD81 and hepatitis C virus in hepatoma mobility. Viruses 2014; 6:1454-72. [PMID: 24662676 PMCID: PMC3970161 DOI: 10.3390/v6031454] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 01/27/2014] [Accepted: 03/05/2014] [Indexed: 12/21/2022] Open
Abstract
Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV) associated HCC. The tetraspanin CD81 is an essential receptor for HCV, however, its role in hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is limited by HCV infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM) proteins in this process. We show enhanced hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-tumor tissue. In summary, these data support a role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour promoter.
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Affiliation(s)
- Claire L Brimacombe
- Viral Hepatitis Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
| | - Garrick K Wilson
- Viral Hepatitis Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
| | - Stefan G Hübscher
- Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
| | - Jane A McKeating
- Viral Hepatitis Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
| | - Michelle J Farquhar
- Viral Hepatitis Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
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Anatomic versus nonanatomic resection in cirrhotic patients with early hepatocellular carcinoma. Surgery 2013; 155:512-21. [PMID: 24439747 DOI: 10.1016/j.surg.2013.10.009] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Accepted: 10/08/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Whether anatomic resection (AR) for hepatocellular carcinoma (HCC) can really confer a survival advantage over non-AR (NAR), especially for cirrhotic patients, remains unclear. METHODS Prospectively collected data of 543 cirrhotic patients in Child-Pugh class A submitted to AR (n = 228) versus NAR (n = 315) for early HCC in an Eastern (n = 269) and a Western (n = 274) surgical unit, were reviewed. To control for confounding variable distributions, a 1-to-1 propensity score match was applied to compare AR and NAR outcomes (n = 298). RESULTS The 5-year recurrence-free and overall survivals of the 543 patients were 32.3% and 60.0%, respectively, without differences between the 2 centers (P = .635 and .479, respectively). AR conferred better overall and recurrence-free survival than NAR (P = .009 and .041, respectively), but NAR patients suffered from significantly worse hepatic dysfunction. After 1-to-1 match, AR (n = 149) and NAR (n = 149) patients had similar covariate distributions. In this matched sample, AR still conferred better recurrence-free survival over NAR (P = .044) but the beneficial effect of AR was limited to the reduction of early recurrence (<2 years) of poorly differentiated tumors and of tumors with microvascular invasion (P < .05), resulting in better overall survival (P = .018). CONCLUSION In cirrhotic patients, AR for early HCC can lead to a lower early recurrence rate in tumors with unfavorable tumor features, whereas NAR will not worsen the recurrence rate in well/moderately differentiated tumors or in the absence of microvascular invasion.
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Lee Cheah Y, K.H. Chow P. Liver transplantation for hepatocellular carcinoma: an appraisal of current controversies. Liver Cancer 2012; 1:183-9. [PMID: 24159583 PMCID: PMC3760462 DOI: 10.1159/000343832] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Cost-effective and efficacious approaches to the management of hepatocellular carcinoma (HCC) must be developed in response to the rising incidence of this disease worldwide. While surgical resection is the current standard of care, most patients afflicted with HCC are unresectable at diagnosis. Developing good therapy for these patients is thus imperative. Liver transplantation offers the possibility of extirpation of not only the tumor but also the remaining cirrhotic liver. Transplantation is hence an ideal treatment option for early HCC patients with poor liver function. When transplantation occurs within the established Milan criteria, the outcomes are good (5-year survival >60%). Current efforts are under way to expand the indications for transplantation beyond the Milan criteria. The resulting surge of new algorithms may potentially shape a new system of transplantation criteria based on personalized parameter calculations. However, this change in criteria is not without controversy, and data remains inconclusive. Current bridging strategies have been similarly hindered by lack of consensus because of the lack of randomized, controlled trials demonstrating their efficacy. In addition, debate continues on the role of transplantation in early (resectable) HCC with good liver function. Issues of reimbursement, the paucity of available donor livers, and governmental funding (or lack thereof) continue to complicate the situation. In this review, issues preventing or facilitating globally consistent treatment strategies for HCC are discussed.
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Affiliation(s)
- Yee Lee Cheah
- Hepatobiliary and Pancreatic Surgery, Department of Surgery, Khoo Teck Puat Hospital, Singapore
| | - Pierce K.H. Chow
- General Surgery Department, Singapore General Hospital, Singapore,Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore,Department of Surgical Oncology, National Cancer Center Singapore, Singapore,*General Surgery Department, Singapore General Hospital, Outram Road, 169608 (Singapore), Tel. +65 96708129, E-Mail
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van Malenstein H, Komuta M, Verslype C, Vandecaveye V, Van Calster B, Topal B, Laleman W, Cassiman D, Van Steenbergen W, Aerts R, Vanbeckevoort D, Bielen D, Pirenne J, van Pelt J, Roskams T, Nevens F. Histology obtained by needle biopsy gives additional information on the prognosis of hepatocellular carcinoma. Hepatol Res 2012; 42:990-8. [PMID: 22548688 DOI: 10.1111/j.1872-034x.2012.01010.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
AIM Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner. METHODS Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α-fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression. RESULTS Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1-74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86-10.6), which improved predictive performance. No needle tract dissemination was observed. CONCLUSION Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.
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Affiliation(s)
- Hannah van Malenstein
- Departments of Hepatology Pathology Radiology Biostatistics Cell, Leuvens KankerinstituutDepartments of Abdominal Surgery Abdominal Transplant Surgery, University Hospital Leuven Department of Electrical Engineering (ESAT), Catholic University Leuven, Leuven, Belgium
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Sersté T, Barrau V, Ozenne V, Vullierme MP, Bedossa P, Farges O, Valla DC, Vilgrain V, Paradis V, Degos F. Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy. Hepatology 2012; 55:800-6. [PMID: 22006503 DOI: 10.1002/hep.24746] [Citation(s) in RCA: 123] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Accepted: 09/25/2011] [Indexed: 12/26/2022]
Abstract
UNLABELLED Liver macronodules, ranging from benign to low-grade or high-grade dysplastic nodules (LGDNs/HGDNs) and hepatocellular carcinoma (HCC), may develop during chronic liver diseases (CLDs). Current guidelines were recently updated and the noninvasive criteria for the diagnosis of small HCC are based on a single typical radiological pattern and nonconclusive coincidental findings with two techniques. This study aimed to assess the accuracy and disagreements of noninvasive multiphasic examinations for the diagnosis of HCC and dysplastic nodules (DNs) and the role of biopsy. Seventy-four consecutive patients with CLD with ultrasound-detected 1-2-cm nodules underwent, within 1 month, multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and biopsy of the nodule. Median age was 60 years; 33 patients (45%) had hepatitis C virus, 20 (27%) had hepatitis B virus, and 13 (18%) patients had no cirrhosis. Biopsy revealed 47 HCCs, 6 HGDNs, 1 LGDNs, 1 cholangiocarcinoma, and 1 epithelioid hemangioendothelioma. There were no tumors in the other 18 patients. All patients (31 of 31; 100%) who had conclusive coincidental findings (i.e., arterial enhancement and washout) on both examinations had HCC or HGDN (sensitivity, 57%; specificity, 100%). All patients (51 of 51; 100%) who had conclusive findings on at least one of the two examinations had HCC or HGDN (sensitivity, 96%; specificity, 100%). There was a disagreement regarding imaging findings between CT and MRI in 21 of 74 (28%) patients and no washout on both examinations in 23 of 74 patients (31%). In these 44 patients, liver biopsy provided an initial accurate diagnosis. CONCLUSION The noninvasive diagnosis of HCC or HGDN can be obtained if arterial enhancement and washout are found in a single dynamic imaging examination. These findings are frequently discordant on both CT and MRI, supporting the place of biopsy for the diagnosis of small HCCs.
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Affiliation(s)
- Thomas Sersté
- Assistance-Publique Hôpitaux de Paris, APHP Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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Parisi G. Should a radiological diagnosis of hepatocellular carcinoma be routinely confirmed by a biopsy? Yes. Eur J Intern Med 2012; 23:34-6. [PMID: 22153528 DOI: 10.1016/j.ejim.2011.10.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Revised: 10/19/2011] [Accepted: 10/20/2011] [Indexed: 12/20/2022]
Abstract
Hepatocellular carcinoma (HCC) represents approximately 85 to 90% of all primary liver cancers (PLC) and every year, more than 560,000 people are diagnosed as affected by this cancer. The identification of risk factors for HCC prompted the creation of screening and surveillance programs in patients affected by chronic liver diseases with the aim of detecting HCC nodules as soon as possible and provide effective and hopefully curative therapy A correct diagnosis is of paramount importance for the surveillance program as well as for the choice of the appropriate therapy. Both in the diagnosis of small HCC and in the choice of the therapy for locally advanced HCC the diagnosis must be certain. Improvements of the radiological imagine techniques have surely enhanced both early diagnosis and tumor staging, allowing a reasonably accurate diagnosis, but cannot provide the certainty that in clinical practice is essential for an adequate workout. Therefore, the histopatological definition of the tumor is imperative both for an appropriate therapy and for an accurate prognostic evaluation.
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Affiliation(s)
- Giancarlo Parisi
- Department of Internal Medicine, S.Maria del Prato Hospital, 32032 Feltre (BL), Italy.
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Zhong JH, Ma L, Wu LC, Zhao W, Yuan WP, Wu FX, Zhang ZM, Huang S, You XM, Li LQ. Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review. Int J Clin Pract 2012; 66:21-7. [PMID: 22171902 DOI: 10.1111/j.1742-1241.2011.02814.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post-operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease-free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease-free survival rate or recurrence rate.
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Affiliation(s)
- J-H Zhong
- Hepatobiliary Surgery Department of Tumor Hospital, Guangxi Medical University, Nanning, China
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Abstract
Hepatocellular carcinoma represents the main cause of death in patients with Child-A cirrhosis. Surveillance programs aimed at the early diagnosis of hepatocellular carcinoma, at potentially treatable stages, are mandatory in Child-A cirrhotic patients and in Child-B cirrhotic patients, provided liver transplantation can be pursued. Surveillance allows stage migration and in definite subgroups of patients, it improves survival as well. Even though several circulating markers have been tested, none of them, including serum AFP determination, is actually recommended in the setting of surveillance. Thus ultrasound scan is the only recommended test, and it should be performed at 6-month intervals. Upon detection of a new nodule, a diagnostic algorithm based on the size of the nodule should be applied. In the western countries, the BCLC proposal is the most widely used and validated staging system and it helps to choice of the best treatment option even though each patient deserves a multidisciplinary evaluation due to the complexity of the coexistence of two diseases: hepatocellular carcinoma and liver cirrhosis.
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Affiliation(s)
- Luigi Bolondi
- Department of Digestive Diseases and Internal Medicine, University of Bologna-Policlinico S. Orsola Malpighi Bologna, Via Albertoni 15, Bologna, Italy.
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