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Zhai Y, Wang L, Zhao H, Wu F, Xin L, Ye F, Sun W, Song Y, Niu L, Zeng H, Wang J, Tang Y, Song Y, Liu Y, Fang H, Lu N, Jing H, Qi S, Zhang W, Wang S, Li YX, Wu J, Chen B. Phase II study with sorafenib plus radiotherapy for advanced HCC with portal and/or hepatic vein tumor thrombosis. JHEP Rep 2025; 7:101287. [PMID: 39980754 PMCID: PMC11840495 DOI: 10.1016/j.jhepr.2024.101287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/01/2024] [Accepted: 11/20/2024] [Indexed: 02/22/2025] Open
Abstract
Background & Aims Portal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis. Methods Registered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events. Results Between May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events. Conclusions Concurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis. Impact and implications Treatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis. Clinical trials registration This study is registered at ClinicalTrials.gov (NCT03535259).
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Affiliation(s)
- Yirui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingxia Xin
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Sun
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Song
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lijuan Niu
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huiying Zeng
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingbo Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Tang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongwen Song
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yueping Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ningning Lu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hao Jing
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shunan Qi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenwen Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shulian Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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El Ouardi W, El Mansoury FZ, Benazzouz M. Unusual location of metastatic lymph nodes of hepatocellular carcinoma in the mediastinum: Case report. Radiol Case Rep 2025; 20:285-288. [PMID: 39525899 PMCID: PMC11546455 DOI: 10.1016/j.radcr.2024.10.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatocellular carcinoma is an aggressive tumor that typically metastasizes to the lungs, abdominal lymph nodes, and bones. The presence of mediastinal lymph node metastases is a rare and unusual clinical situation, associated with a poor prognosis. We report the case of a patient with cirrhosis secondary to treated hepatitis C, in whom hepatocellular carcinoma was discovered without extrahepatic spread, except for the presence of mediastinal lymphadenopathy. Biopsy of these nodes, performed via endoscopic ultrasound-guided fine needle biopsy through the oesophagus, confirmed that they were indeed metastatic mediastinal lymph node metastases from HCC. This finding shifted the therapeutic approach from curative treatment to systemic therapy.
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Affiliation(s)
- Walid El Ouardi
- Gastroenterology Department, Faculty of Medicine and Pharmacy, Rabat, Morocco
| | | | - Mustapha Benazzouz
- Department of Gastroenterology, International University of Rabat/Riad Annakhil International Polyclinic, Rabat, Morocco
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Aralica M, Nadarevic T, Colli A, Casazza G, Vranić L, Fraquelli M, Poropat G, Štimac D. GALAD, or des-gamma-carboxy prothrombin compared with alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in people with chronic liver disease. Cochrane Database Syst Rev 2024; 12:CD015826. [PMID: 39688172 PMCID: PMC11650702 DOI: 10.1002/14651858.cd015826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To estimate the diagnostic accuracy of des-gamma-carboxy prothrombin, GALAD (Gender, Age, Lens culinaris agglutinin-reactive AFP, AFP and DCP), and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma of any size, and at any stage, in adults with chronic liver disease, in either a surveillance programme or a clinical setting. We acknowledge the possibility that theoretically, the accuracy of the tests in a surveillance programme may differ from that in a clinical setting due to variation in inclusion criteria and the prevalence of the target condition. However, we do not plan a separate analysis for surveillance and clinical settings, as they are not clearly distinct in current clinical practice (Forner 2018; Poustchi 2011). In routine evaluation of people with chronic liver disease, index tests, as well as ultrasound, are already part of standard procedure. Given that HCC typically presents with no symptoms and is often asymptomatic, suspicion of the disease is typically based solely on the presence of advanced chronic liver disease. However, we do plan to consider the study setting as a potential source of heterogeneity. To compare the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP) alone or GALAD alone versus alpha-foetoprotein (AFP), for the diagnosis of hepatocellular carcinoma (HCC) of any size, at any stage; in adults with chronic liver disease, either in a surveillance programme or a clinical setting. Secondary objectives To estimate the diagnostic accuracy of DCP or GALAD versus AFP, for resectable HCC in people with chronic liver disease, in a surveillance programme and a clinical setting. To investigate the following predefined sources of heterogeneity for each of the index tests: study design (case-control studies compared to cross-sectional studies); inclusion of participants without cirrhosis (studies including more than 10% of participants without cirrhosis compared to studies including less than 10% of participants without cirrhosis); study location (population differences): studies conducted in North and South America and Europe compared to Asia and Africa; prevalence of the target condition (studies with hepatocellular carcinoma prevalence more than 10% compared to studies with hepatocellular carcinoma prevalence less than 10%); participant selection (participants recruited from planned surveillance programmes compared to clinical cohorts); different reference standards (histology of the explanted liver compared to liver biopsy compared to another reference standard); different aetiology: studies including at least 90% of participants with chronic viral hepatitis compared to studies including less than 90% of participants with chronic viral hepatitis.
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Affiliation(s)
- Merica Aralica
- Clinical Department of Laboratory Diagnostics, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Luka Vranić
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milano, Milan, Italy
| | - Goran Poropat
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
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Sakata Y, Nomura H, Nakajima H, Kitajima T, Ito Y, Yamamoto Y. Impact of telephone follow-up on hepatocellular carcinoma patients receiving oral chemotherapy from an ambulatory-care setting. J Oncol Pharm Pract 2024; 30:1378-1384. [PMID: 38043932 DOI: 10.1177/10781552231215427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
INTRODUCTION In recent years, most molecular target drugs have been administered orally, as prescribed at ambulatory services in hospitals and at patients' homes. Telephone follow-up is increasingly being used in clinical practice for patients needing additional support post-discharge and for the prevention of hospital readmissions. The purpose of this study was to clarify the clinical benefits of telephone follow-up while administering oral anticancer drugs. METHODS This was a single-center, observational, retrospective study. We evaluated hepatocellular carcinoma patients who received sorafenib or lenvatinib between March 2010 and February 2018. The primary endpoint was the incidence of adverse events. RESULTS From the total of 130 patients, 83 patients received telephone follow-up and 47 did not. The incidence of hand-foot skin reactions significantly reduced in patients with telephone follow-up (odds ratio (OR) 3.69, 95% confidence interval (CI) 1.16-11.8, p = 0.020). The median durations (ranges) of adherence to oral chemotherapy were 259 days (15-1730) for the telephone follow-up group and 121 days (14-1105) for the no-telephone follow-up group (p < 0.001). Moreover, the disease control rate was significantly higher in the telephone follow-up group (OR 2.52, 95% CI 1.15-5.53, p = 0.020). CONCLUSIONS Remote interventions, such as telephone follow-up, are useful means of managing adverse events in patients receiving oral anticancer drugs and can lead to improved treatment results.
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Affiliation(s)
- Yukio Sakata
- Department of Pharmacy, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Hisanaga Nomura
- Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
- Clinical Research Support Office, Seeds Development Promotion Department, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Hirofumi Nakajima
- Department of Pharmacy, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Tomomi Kitajima
- Department of Nursing, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Yukiko Ito
- Department of Nursing, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Yoshiya Yamamoto
- Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Hakodate, Japan
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Chang YJ, Chang YJ, Chen LJ. Prognostic factors in patients with intrahepatic cholangiocarcinoma. Sci Rep 2024; 14:19084. [PMID: 39154139 PMCID: PMC11330494 DOI: 10.1038/s41598-024-70124-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan-Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25-201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I-III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.
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Affiliation(s)
- Yun-Jau Chang
- Department of General Surgery, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan
- Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Yao-Jen Chang
- Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
| | - Li-Ju Chen
- Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan.
- University of Taipei, Taipei, Taiwan.
- Division of Surgery, Heping Branch, Taipei City Hospital, No. 33, Section 2, ZhongWha Rd., ZhongZheng District, Taipei, 10065, Taiwan.
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Fu YK, Li YN, Liu DY, Zeng ZX, Wu JY, Wu JY, Wang JX, Li H, Ou XY, Yan ML. Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review. Oncol Res Treat 2024; 47:465-473. [PMID: 39111295 DOI: 10.1159/000540662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 07/29/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.
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Affiliation(s)
- Yang-Kai Fu
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - De-Yi Liu
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhen-Xin Zeng
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jin-Xiu Wang
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Han Li
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Xiang-Ye Ou
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
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Liu Q, Zhang Y, Zhang J, Chen L, Yang Y, Liu Y. Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis in the main trunk. Front Oncol 2024; 14:1374149. [PMID: 39077472 PMCID: PMC11284057 DOI: 10.3389/fonc.2024.1374149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
Purpose To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software. Results A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250-7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin. Conclusion FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT. Clinical signicance FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.
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Affiliation(s)
| | | | | | | | | | - Yan Liu
- Department of Interventional Radiology, Harbin Medical University Cancer Hospital, Harbin, China
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Islam MR, Rauf A, Alash S, Fakir MNH, Thufa GK, Sowa MS, Mukherjee D, Kumar H, Hussain MS, Aljohani ASM, Imran M, Al Abdulmonem W, Thiruvengadam R, Thiruvengadam M. A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways. Med Oncol 2024; 41:134. [PMID: 38703282 DOI: 10.1007/s12032-024-02333-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 02/13/2024] [Indexed: 05/06/2024]
Abstract
Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Alash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Md Naeem Hossain Fakir
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Gazi Kaifeara Thufa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Mahbuba Sharmin Sowa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Dattatreya Mukherjee
- Raiganj Government Medical College and Hospital, Pranabananda Sarani, Raiganj, 733134, West Bengal, India
| | - Harendra Kumar
- Dow University of Health Sciences, Mission Rd, New Labour Colony Nanakwara, Karachi, 74200, Sindh, Pakistan
| | - Md Sadique Hussain
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, 302017, Rajasthan, India
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Muhammad Imran
- Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, 61413, Abha, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Rekha Thiruvengadam
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical & Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, South Korea
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Okazaki S, Shibuya K, Shiba S, Takura T, Ohno T. Cost-Effectiveness Comparison of Carbon-Ion Radiation Therapy and Transarterial Chemoembolization for Hepatocellular Carcinoma. Adv Radiat Oncol 2024; 9:101441. [PMID: 38778825 PMCID: PMC11110039 DOI: 10.1016/j.adro.2024.101441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 01/03/2024] [Indexed: 05/25/2024] Open
Abstract
PURPOSE Carbon-ion radiation therapy (CIRT) is a treatment option for patients with hepatocellular carcinoma (HCC) that results in better outcomes with fewer side effects despite its high cost. This study aimed to evaluate the cost-effectiveness of CIRT for HCC from medical and economic perspectives by comparing CIRT and transarterial chemoembolization (TACE) in patients with localized HCC who were ineligible for surgery or radiofrequency ablation. METHODS AND MATERIALS This study included 34 patients with HCC who underwent either CIRT or TACE at Gunma University between 2007 and 2016. Patient characteristics were employed to select each treatment group using the propensity score matching method. Life years were used as the outcome indicator. The CIRT technical fee was ¥3,140,000; however, a second CIRT treatment on the same organ within 2 years was performed for free. RESULTS Our study showed that CIRT was dominant over TACE, as the CIRT group had a higher life year (point estimate, 2.75 vs 2.41) and lower total cost (mean, ¥4,974,278 vs ¥5,284,524). We conducted a sensitivity analysis to validate the results because of the higher variance in medical costs in the TACE group, which demonstrated that CIRT maintained its cost effectiveness with a high acceptability rate. CONCLUSIONS CIRT is a cost-effective treatment option for localized HCC cases unsuitable for surgical resection.
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Affiliation(s)
- Shohei Okazaki
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan
- Department of Radiology, Gunma Prefectural Cancer Center, Ota, Japan
| | - Kei Shibuya
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Shintaro Shiba
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Tomoyuki Takura
- Department of Health Care Services Management, Nihon University School of Medicine, Tokyo, Japan
- Department of Healthcare Economics and Health Policy, University of Tokyo, Tokyo, Japan
| | - Tatsuya Ohno
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan
- Gunma University Heavy Ion Medical Center, Showa-machi, Maebashi, Japan
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Wu F, Ni X, Sun H, Zhou C, Huang P, Xiao Y, Yang L, Yang C, Zeng M. An MRI-Based Prognostic Stratification System for Medical Decision-Making of Multinodular Hepatocellular Carcinoma Patients Beyond the Milan Criteria. J Magn Reson Imaging 2023; 58:1918-1929. [PMID: 37083126 DOI: 10.1002/jmri.28724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/23/2023] [Accepted: 03/23/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND The suitability of hepatectomy among patients with multinodular hepatocellular carcinoma (MHCC) beyond the Milan criteria remains controversial. There is a need for a reliable risk stratification tool among these patients for the selection of ideal candidates of curative resection. PURPOSE To determine the clinicoradiological prognostic factors for patients with MHCC beyond the Milan criteria to further develop a stratification system. STUDY TYPE Retrospective. SUBJECTS 176 patients with pathologically confirmed MHCC beyond the Milan criteria. FIELD STRENGTH/SEQUENCE The 1.5 T scanner, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT Conventional MRI features and preoperative laboratory data including aspartate aminotransferase (AST) and α-fetoprotein (AFP) were collected and analyzed. Two nomograms incorporating clinicoradiological variables were independently constructed to predict recurrence-free survival (RFS) and overall survival (OS) with Cox regression analyses and verified with 5-fold cross validation. Based on the nomograms, two prognostic stratification systems for RFS and OS were further developed. STATISTICAL TESTS The Cohen's kappa/intraclass correlation coefficient, C-index, calibration curve, Kaplan-Meier curve, log-rank test. A P value <0.05 was considered statistically significant. RESULTS AST > 40 U/L, increased tumor burden score, radiological liver cirrhosis and nonsmooth tumor margin were independent predictors for poor RFS, while AST > 40 U/L, AFP > 400 ng/mL and radiological liver cirrhosis were independent predictors for poor OS. The two nomograms demonstrated good discrimination performance with C-index of 0.653 (95% confidence interval [CI], 0.602-0.794) and 0.685 (95% CI, 0.623-0.747) for RFS and OS, respectively. The 5-fold cross validation further validated the discrimination capability of the nomograms. Based on the nomogram models, MHCC patients beyond the Milan criteria were stratified into low-/medium-/high-risk groups with significantly different RFS and OS. DATA CONCLUSION The proposed MRI-based prognostic stratification system facilitates the refinement and further subclassification of patients with MHCC beyond the Milan criteria. EVIDENCE LEVEL 4. TECHNICAL EFFICACY 2.
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Affiliation(s)
- Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Ni
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haitao Sun
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
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11
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Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, Yopp AC, Zhou J, Wang L, Wen X, Heo J, Tak WY, Nakamura S, Numata K, Uguen T, Hsiehchen D, Cha E, Hack SP, Lian Q, Ma N, Spahn JH, Wang Y, Wu C, Chow PKH. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023; 402:1835-1847. [PMID: 37871608 DOI: 10.1016/s0140-6736(23)01796-8] [Citation(s) in RCA: 187] [Impact Index Per Article: 93.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 08/04/2023] [Accepted: 08/22/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. METHODS In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. FINDINGS The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. INTERPRETATION Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. FUNDING F Hoffmann-La Roche/Genentech.
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Affiliation(s)
- Shukui Qin
- Jinling Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Minshan Chen
- Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ann-Lii Cheng
- National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
| | - Ahmed O Kaseb
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jian Zhou
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lu Wang
- Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaoyu Wen
- 1st Hospital of Jilin University, Jilin, China
| | - Jeong Heo
- College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Won Young Tak
- Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea
| | | | - Kazushi Numata
- Yokohama City University Medical Center, Yokohama, Japan
| | | | - David Hsiehchen
- Department of Internal Medicine, Division of Hematology and Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | | | | | - Ning Ma
- Genentech, South San Francisco, CA, USA
| | | | - Yulei Wang
- Fudan University Shanghai Cancer Center, Shanghai, China; Genentech, South San Francisco, CA, USA
| | - Chun Wu
- Roche (China) Holding, Shanghai, China
| | - Pierce K H Chow
- National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, Singapore.
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Naganuma H, Ishida H. Hepatocellular Carcinoma in Non-Fibrotic Liver: A Narrative Review. Diagnostics (Basel) 2023; 13:3426. [PMID: 37998562 PMCID: PMC10670297 DOI: 10.3390/diagnostics13223426] [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: 10/30/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023] Open
Abstract
Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion's large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function. Although detailed clinical data are very limited, we expect that this review will help to improve the clinical management of HCC in non-fibrotic livers.
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Affiliation(s)
- Hiroko Naganuma
- Department of Gastroenterology, Yokote Municipal Hospital, Negishi-cho 5-31, Yokote City 013-8602, Japan
| | - Hideaki Ishida
- Department of Gastroenterology, Akita Red Cross Hospital, Kamikitate Saruta aza Naeshirosawa 222-1, Akita City 010-1495, Japan
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Iijima H, Kudo M, Kubo S, Kurosaki M, Sakamoto M, Shiina S, Tateishi R, Osamu N, Fukumoto T, Matsuyama Y, Murakami T, Takahashi A, Miyata H, Kokudo N. Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015). Hepatol Res 2023; 53:895-959. [PMID: 37574758 DOI: 10.1111/hepr.13953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/01/2023] [Indexed: 08/15/2023]
Abstract
For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20 889 newly registered patients and 42 274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.
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Affiliation(s)
- Hiroko Iijima
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Masatoshi Kudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Shoji Kubo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masayuki Kurosaki
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michiie Sakamoto
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- School of Medicine, International University of Health and Welfare, Tokyo, Japan
| | - Shuichiro Shiina
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nakashima Osamu
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Takamichi Murakami
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Arata Takahashi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Center for Global Health and Medicine, Tokyo, Japan
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Rijken A, Bakkers C, Klümpen HJ, van der Geest LG, de Vos-Geelen J, van Erning FN, de Hingh IHJT. Insights into synchronous peritoneal metastases from hepatobiliary origin: Incidence, risk factors, treatment, and survival from a nationwide database. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1436-1443. [PMID: 36898900 DOI: 10.1016/j.ejso.2023.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/21/2023] [Accepted: 03/02/2023] [Indexed: 03/07/2023]
Abstract
INTRODUCTION - This population-based study aimed to investigate incidence, risk factors, treatment, and survival of synchronous peritoneal metastases (PM) of hepatobiliary origin. METHODS - All Dutch patients diagnosed with hepatobiliary cancer between 2009 and 2018 were selected. Factors associated with PM were identified with logistic regression analyses. Treatments for patients with PM were categorized into local therapy, systemic therapy, and best supportive care (BSC). Overall survival (OS) was investigated using log-rank test. RESULTS - In total, 12 649 patients were diagnosed with hepatobiliary cancer of whom 8% (n = 1066) were diagnosed with synchronous PM (12% [n = 882/6519] in biliary tract cancer [BTC] vs. 4% [n = 184/5248] in hepatocellular carcinoma [HCC]). Factors that were positively associated with PM were the female sex (OR 1.18, 95% CI 1.03-1.35), BTC (OR 2.93, 95% CI 2.46-3.50), diagnosis in more recent years (2013-2015: OR 1.42, 95% CI 1.20-1.68; 2016-2018: OR 1.48, 95% CI 1.26-1.75), T3/T4 stage (OR 1.84, 95% CI 1.55-2.18), N1/N2 stage (OR 1.31, 95% CI 1.12-1.53) and other synchronous systemic metastases (OR 1.85, 95% CI 1.62-2.12). Of all PM patients, 723 (68%) received BSC only. Median OS was 2.7 months (IQR 0.9-8.2) in PM patients. CONCLUSION - Synchronous PM were found in 8% of all hepatobiliary cancer patients and occurred more often in BTC than in HCC. Most patients with PM received BSC only. Given the high incidence and dismal prognosis of PM patients, extended research in hepatobiliary PM is needed to achieve better outcome in these patients.
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Affiliation(s)
- Anouk Rijken
- Department of Surgery, Catharina Cancer Institute, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization, Godebaldkwartier 419, 3511 DT, Utrecht, the Netherlands
| | - Checca Bakkers
- Department of Surgery, Catharina Cancer Institute, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
| | - Lydia G van der Geest
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Godebaldkwartier 419, 3511 DT, Utrecht, the Netherlands
| | - Judith de Vos-Geelen
- Department of Internal Medicine, Division of Medical Oncology, Maastricht UMC+, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands; GROW, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Cancer Institute, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization, Godebaldkwartier 419, 3511 DT, Utrecht, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Cancer Institute, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization, Godebaldkwartier 419, 3511 DT, Utrecht, the Netherlands; GROW, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, the Netherlands.
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Wu F, Sun H, Shi Z, Zhou C, Huang P, Xiao Y, Yang C, Zeng M. Estimating Microvascular Invasion in Patients with Resectable Multinodular Hepatocellular Carcinoma by Using Preoperative Contrast-Enhanced MRI: Establishment and Validation of a Risk Score. J Hepatocell Carcinoma 2023; 10:1143-1156. [PMID: 37492267 PMCID: PMC10364817 DOI: 10.2147/jhc.s410237] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 07/07/2023] [Indexed: 07/27/2023] Open
Abstract
Objective To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system. Methods Two hundred and seventy-three patients with pathologically confirmed mHCC (≥2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort. Results AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001). Conclusion The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.
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Affiliation(s)
- Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Haitao Sun
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Zhang Shi
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
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Wu F, Sun H, Zhou C, Huang P, Xiao Y, Yang C, Zeng M. Prognostic factors for long-term outcome in bifocal hepatocellular carcinoma after resection. Eur Radiol 2023; 33:3604-3616. [PMID: 36700957 DOI: 10.1007/s00330-023-09398-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 12/14/2022] [Accepted: 12/23/2022] [Indexed: 01/27/2023]
Abstract
OBJECTIVES This study aimed to evaluate whether the radiological similarity and clinicopathological factors determine the prognosis in bifocal hepatocellular carcinoma (bHCC) stratified by the Milan criteria. METHODS Consecutive patients with pathologically confirmed bHCC examined between January 2016 and December 2018 were retrospectively enrolled and grouped based on the Milan criteria. Two radiologists independently evaluated whether the imaging features of both tumors were consistent or not, which was defined as the radiological similarity. The clinicopathological data were also collected. The multivariable Cox regression was applied to separately identify the independent factors for recurrence-free survival (RFS) and overall survival (OS) in bHCC within and beyond the Milan criteria. RESULTS A total of 193 patients were evaluated and divided into the within the Milan criteria group (n = 72) and the beyond the Milan criteria group (n = 121). bHCC within the Milan criteria showed a significantly better prognosis than those beyond the criteria. In the within the Milan criteria group, HBV-DNA load >104 IU/mL, microvascular invasion (MVI), and different enhancement patterns were independently associated with poor RFS. MVI was an independent prognostic factor for poor OS. In the beyond the Milan criteria group, HBV infection, MVI, increased ratio of the larger to the smaller tumor diameter (RLSD) value, and low comprehensive similarity were associated with shorter RFS, whereas MVI and increased RLSD value were independent predictors for poor OS. CONCLUSIONS Our study revealed that in addition to MVI- and HBV-related factors, similarity in imaging features between lesions of bHCC is associated with the long-term prognosis. KEY POINTS • The prognosis of bifocal HCC patients within the Milan criteria is significantly better than those beyond the criteria. • The similarity in imaging features between lesions of bHCC was an independent prognostic factor. • The more similar the bifocal lesions are in imaging features, the better the prognosis is.
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Affiliation(s)
- Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Haitao Sun
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Shanghai Institute of Medical Imaging, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Shanghai Institute of Medical Imaging, Shanghai, China.
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17
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Jansson H, Villard C, Nooijen LE, Ghorbani P, Erdmann JI, Sparrelid E. Prognostic influence of multiple hepatic lesions in resectable intrahepatic cholangiocarcinoma: A systematic review and meta-analysis. Eur J Surg Oncol 2023; 49:688-699. [PMID: 36710214 DOI: 10.1016/j.ejso.2023.01.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/14/2022] [Accepted: 01/07/2023] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Presence of multiple hepatic lesions in intrahepatic cholangiocarcinoma (iCCA) is included in staging as a negative prognostic factor, but both prognostic value and therapeutic implications remain debated. The aim of this study was to systematically review the prognostic influence of multiple lesions on survival after resection for iCCA, with stratification for distribution and number of lesions. METHODS Medline and Embase were systematically searched to identify records (2010-2021) reporting survival for patients undergoing primary resection for iCCA. Included were original articles reporting overall survival, with data on multiple lesions including tumour distribution (satellites/other multiple lesions) and/or number. For meta-analysis, the random effects model and inverse variance method were used. PRISMA 2020 guidelines were followed. RESULTS Thirty-one studies were included for review. For meta-analysis, nine studies reporting data on the prognostic influence of satellite lesions (2737 patients) and six studies reporting data on multiple lesions other than satellites (1589 patients) were included. Satellite lesions (hazard ratio 1.89, 95% confidence interval 1.67-2.13) and multiple lesions other than satellites (hazard ratio 2.41, 95% confidence interval 1.72-3.37) were significant negative prognostic factors. Data stratified for tumour number, while limited, indicated increased risk per additional lesion. CONCLUSION Satellite lesions, as well as multiple lesions other than satellites, was a negative prognostic factor in resectable iCCA. Considering the prognostic impact, both tumour distribution and number of lesions should be evaluated together with other risk factors to allow risk stratification for iCCA patients with multiple lesions, rather than precluding resection for the entire patient group.
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Affiliation(s)
- Hannes Jansson
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
| | - Christina Villard
- Gastroenterology and Rheumatology Unit, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Lynn E Nooijen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Joris I Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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18
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Yang C, Zhang S, Cheng Z, Liu Z, Zhang L, Jiang K, Geng H, Qian R, Wang J, Huang X, Chen M, Li Z, Qin W, Xia Q, Kang X, Wang C, Hang H. Multi-region sequencing with spatial information enables accurate heterogeneity estimation and risk stratification in liver cancer. Genome Med 2022; 14:142. [PMID: 36527145 PMCID: PMC9758830 DOI: 10.1186/s13073-022-01143-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 11/22/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Numerous studies have used multi-region sampling approaches to characterize intra-tumor heterogeneity (ITH) in hepatocellular carcinoma (HCC). However, conventional multi-region sampling strategies do not preserve the spatial details of samples, and thus, the potential influences of spatial distribution on patient-wise ITH (represents the overall heterogeneity level of the tumor in a given patient) have long been overlooked. Furthermore, gene-wise transcriptional ITH (represents the expression pattern of genes across different intra-tumor regions) in HCC is also under-explored, highlighting the need for a comprehensive investigation. METHODS To address the problem of spatial information loss, we propose a simple and easy-to-implement strategy called spatial localization sampling (SLS). We performed multi-region sampling and sequencing on 14 patients with HCC, collecting a total of 75 tumor samples with spatial information and molecular data. Normalized diversity score and integrated heterogeneity score (IHS) were then developed to measure patient-wise and gene-wise ITH, respectively. RESULTS A significant correlation between spatial and molecular heterogeneity was uncovered, implying that spatial distribution of sampling sites did influence ITH estimation in HCC. We demonstrated that the normalized diversity score had the ability to overcome sampling location bias and provide a more accurate estimation of patient-wise ITH. According to this metric, HCC tumors could be divided into two classes (low-ITH and high-ITH tumors) with significant differences in multiple biological properties. Through IHS analysis, we revealed a highly heterogenous immune microenvironment in HCC and identified some low-ITH checkpoint genes with immunotherapeutic potential. We also constructed a low-heterogeneity risk stratification (LHRS) signature based on the IHS results which could accurately predict the survival outcome of patients with HCC on a single tumor biopsy sample. CONCLUSIONS This study provides new insights into the complex phenotypes of HCC and may serve as a guide for future studies in this field.
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Affiliation(s)
- Chen Yang
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Senquan Zhang
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhuoan Cheng
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhicheng Liu
- grid.412793.a0000 0004 1799 5032Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linmeng Zhang
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kai Jiang
- grid.16821.3c0000 0004 0368 8293Renji Biobank, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haigang Geng
- grid.16821.3c0000 0004 0368 8293Department of Gastrointestinal Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ruolan Qian
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Wang
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaowen Huang
- grid.16821.3c0000 0004 0368 8293Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mo Chen
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhe Li
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenxin Qin
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiang Xia
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaonan Kang
- grid.16821.3c0000 0004 0368 8293Renji Biobank, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cun Wang
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hualian Hang
- grid.16821.3c0000 0004 0368 8293Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.16821.3c0000 0004 0368 8293State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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19
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Nakano M, Torisu Y, Nakagawa C, Ueda K, Kanai T, Saeki C, Oikawa T, Saruta M. Safety and efficacy of pentazocine–midazolam combination for pain and anxiety relief in radiofrequency ablation therapy for hepatocellular carcinoma. JGH Open 2022; 6:569-576. [PMID: 35928702 PMCID: PMC9344584 DOI: 10.1002/jgh3.12788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 06/20/2022] [Accepted: 06/23/2022] [Indexed: 12/24/2022]
Abstract
Background and Aim Radiofrequency ablation (RFA) therapy is frequently used as first‐line treatment for small hepatocellular carcinoma (HCC). RFA is often associated with pain; however, no definitive solution has been established for its relief. We retrospectively analyzed the safety and efficacy of the combination of pentazocine and midazolam to relieve pain experienced by HCC patients undergoing RFA. Methods We studied 77 patients with 98 HCCs treated with RFA between January 2015 and August 2019. Patients were divided into two groups: the sedative‐free group, which included those who received pentazocine alone, and the pentazocine–midazolam group, which included those who received a combination of pentazocine and midazolam. The degrees of analgesia and sedation were evaluated using the numerical rating scale (NRS) and the Richmond Agitation‐Sedation Scale (RASS), respectively. Other parameters such as treatment time, awakening time, midazolam dosage, vital signs, local recurrence rate, and time to recurrence were also examined. Results The median NRS score and RASS score were significantly lower in the pentazocine–midazolam group. Ninety‐five percent of patients in the pentazocine–midazolam group had no memory of the RFA session. The treatment time and awakening time were prolonged for the pentazocine–midazolam group. No significant differences in oxygen saturation, recurrence rates, and time to local recurrence were observed between groups. Conclusion A combination of pentazocine and midazolam is safe and effective for pain and anxiety relief experienced by patients undergoing RFA for local treatment of HCC.
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Affiliation(s)
- Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Chika Nakagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Tomoya Kanai
- Division of Gastroenterology, Department of Internal Medicine Fuji City General Hospital Shizuoka Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
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20
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Alghazawi LOK, Holtermann Entwistle O, Fehervari M, Spalding D. Unusual cause of intraoperative haemorrhage: a lesson for patient counselling. BMJ Case Rep 2022; 15:e247951. [PMID: 35680280 PMCID: PMC9185409 DOI: 10.1136/bcr-2021-247951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a well-known malignant neoplasm of the liver associated with spontaneous haemorrhage in 3%-15% of cases. This complication is life threatening and has a mortality rate of 33%-100%. Despite the frequency and severity of spontaneous haemorrhage, the importance of patient education about this complication has not been highlighted before. There is currently no information available on the NHS UK website, and no publications have addressed the effect of patient education. We present this case report describing a patient who developed classical symptoms of haemorrhage the day before her elective HCC resection, but was unaware of its importance, and thus did not seek medical attention. She was subsequently found to have a large volume haemoperitoneum, anaemia and a ruptured HCC intraoperatively. This case illustrates the significant importance of counselled regarding the symptoms and risk of spontaneous rupture of HCC to prompt early presentation to medical services.
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Affiliation(s)
| | | | - Matyas Fehervari
- HPB Surgery, Imperial College Healthcare NHS Trust and Imperial College London, London, UK
| | - Duncan Spalding
- HPB Surgery, Imperial College Healthcare NHS Trust and Imperial College London, London, UK
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21
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Ariizumi SI, Yamamoto M, Kotera Y, Higuchi R, Yamashita S, Kato T, Hirata Y, Katagiri S, Honda G, Egawa H. Intrahepatic Cholangiocarcinoma With Neither Intrahepatic Metastasis Nor Lymph Node Metastasis Is the Optimal Indication for Hepatectomy With Adjuvant Therapy. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:160-166. [PMID: 35399165 PMCID: PMC8962804 DOI: 10.21873/cdp.10090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 12/23/2021] [Indexed: 06/14/2023]
Abstract
Background/Aim The optimal indication of hepatectomy with adjuvant therapy for intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. Patients and Methods We retrospectively studied 224 patients with ICC who underwent hepatectomy between 2000 and 2019. Prognostic factors for overall survival (OS) were evaluated by univariate and multivariate analysis. A total of 127 patients were treated with adjuvant therapy (62 patients with chemotherapy and 65 patients with immunotherapy) after hepatectomy, and 97 patients were treated with hepatectomy alone. Results Intrahepatic metastasis (IM), lymph node metastasis (LNM) of ICC, adjuvant chemotherapy, and adjuvant immunotherapy were significant prognostic factors for OS on multivariate analysis. In 127 patients with neither IM nor LNM, the 5-year OS rate was significantly higher in 36 patients with adjuvant chemotherapy (81%) and in 34 patients with adjuvant immunotherapy (68%) than in 57 patients with hepatectomy alone (45%). Conclusion The absence of IM or LNM is the optimal indication for hepatectomy with adjuvant therapy in patients with ICC.
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Affiliation(s)
- Shun-Ichi Ariizumi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoshihito Kotera
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Shingo Yamashita
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Takaaki Kato
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoshihiro Hirata
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Satoshi Katagiri
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Goro Honda
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
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22
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Deng ZJ, Li L, Teng YX, Zhang YQ, Zhang YX, Liu HT, Huang JL, Liu ZX, Ma L, Zhong JH. Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Current Status and Controversy. J Clin Transl Hepatol 2022; 10:147-158. [PMID: 35233384 PMCID: PMC8845160 DOI: 10.14218/jcth.2021.00179] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/30/2021] [Accepted: 07/12/2021] [Indexed: 01/27/2023] Open
Abstract
The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.
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Affiliation(s)
| | | | - Yu-Xian Teng
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yu-Qi Zhang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yu-Xin Zhang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Hao-Tian Liu
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jian-Li Huang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Zhen-Xiu Liu
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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23
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Ning Z, Yang L, Yan X, Wang D, Hua Y, Shi W, Lin J, Meng Z. Effect and mechanism of Lenvatinib@H-MnO2-FA drug delivery system in targeting intrahepatic cholangiocarcinoma. Curr Pharm Des 2022; 28:743-750. [PMID: 35049427 DOI: 10.2174/1381612828666220113161712] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 12/14/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND To investigate the effects of the Lenvatinib@H-MnO2-FA administration system on the proliferation and apoptosis of Intrahepatic cholangiocarcinoma (ICC) and the underlying molecular mechanism. MATERIALS AND METHODS In this research, hollow MnO2 (H-MnO2) was synthesized via the modified Stöber method, and H-MnO2 was modified with polyethylene glycol-bis (Amine) (NH2-PEG-NH2) and folic acid (FA) to obtain H-MnO2-PEG-FA (H-MnO2-FA). Lenvatinib was coated in the hollow cavity of H-MnO2-PEG-FA to further form a nanometre drug-carrying system (lenvatinib@H-MnO2-PEG-FA). Lenvatinib@H-MnO2-FA was characterized through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to verify that Lenvatinib was loaded on nanoparticles. Functionally, confocal laser scanning microscopy (CLSM), 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine the effect of lenvatinib@H-MnO2-FA on the proliferation and apoptosis of ICC cells (9810 cells). Finally, the protein levels of Raf-1MEK1/2-ERK1/2 signalling pathway components were detected through Western blotting analysis. RESULTS We successfully synthesised a Lenvatinib@H-MnO2-PEG-FA administration system. The resulting nanomaterials had excellent biological stability and improved targeting effects. Functionally, lenvatinib@H-MnO2-FA inhibited the proliferation of 9810 cells. The Bcl-2 protein level was significantly downregulated, and the caspase-3 protein level was significantly upregulated, indicating that lenvatinib@H-MnO2-PEG-FA promoted the apoptosis of 9810 cells. Mechanistically, Lenvatinib@H-MnO2-FA increased the phosphorylation levels of Raf, MEK1/2 and ERK1/2. CONCLUSIONS H-MnO2-FA can more effectively deliver Lenvatinib to inhibit proliferation and promote apoptosis in ICC, could be the promising drug delivery nano-vehicles for delivery drugs.
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Affiliation(s)
- Zhouyu Ning
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lina Yang
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xia Yan
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Dan Wang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yongqiang Hua
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Weidong Shi
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Junhua Lin
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiqiang Meng
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
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24
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Kudo M, Izumi N, Kokudo N, Sakamoto M, Shiina S, Takayama T, Tateishi R, Nakashima O, Murakami T, Matsuyama Y, Takahashi A, Miyata H, Kubo S. Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013). Hepatol Res 2022; 52:5-66. [PMID: 34050584 DOI: 10.1111/hepr.13675] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/12/2021] [Accepted: 05/15/2021] [Indexed: 12/15/2022]
Abstract
In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.
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Affiliation(s)
- Masatoshi Kudo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Namiki Izumi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Norihiro Kokudo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takamichi Murakami
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Arata Takahashi
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shoji Kubo
- Liver Cancer Study Group of Japan, Follow-up Survey Committee, Japan.,Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Blaise L, Pereira H, Vilgrain V, Sutter O, Gigante E, Walter A, Ganne-Carrié N, Nahon P, Bouattour M, Dioguardi Burgio M, Grando V, Nkontchou G, Seror O, Nault JC. Percutaneous ablation for locally advanced hepatocellular carcinoma with tumor portal invasion. Clin Res Hepatol Gastroenterol 2021; 45:101731. [PMID: 34139320 DOI: 10.1016/j.clinre.2021.101731] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/27/2021] [Accepted: 06/10/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE). METHODS We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics. RESULTS 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo-Clavien III-V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12). CONCLUSION Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE.
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Affiliation(s)
- Lorraine Blaise
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Helena Pereira
- Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France
| | - Valérie Vilgrain
- Service de Radiologie, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France; Université de Paris et CRI, INSERM 1149, F-75018, Paris, France
| | - Olivier Sutter
- Unité de Radiologie Interventionnelle, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Elia Gigante
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Aurélie Walter
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Nathalie Ganne-Carrié
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Pierre Nahon
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Mohamed Bouattour
- Service d'Oncologie Digestive et Médicale, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Marco Dioguardi Burgio
- Service de Radiologie, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France; Université de Paris et CRI, INSERM 1149, F-75018, Paris, France
| | - Véronique Grando
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Gisèle Nkontchou
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Olivier Seror
- Unité de Radiologie Interventionnelle, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.
| | - Jean-Charles Nault
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.
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Khan AR, Wei X, Xu X. Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma - The Changing Tides. J Hepatocell Carcinoma 2021; 8:1089-1115. [PMID: 34522691 PMCID: PMC8434852 DOI: 10.2147/jhc.s318070] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.
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Affiliation(s)
- Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
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Abstract
OBJECTIVE To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe. BACKGROUND Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown. METHODS We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function. RESULTS According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026). CONCLUSIONS Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.
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Yamazaki S, Takayama T, Aoki M, Yoshida N, Higaki T. High dorsal resection for hepatocellular carcinoma: surgical plane and outcomes. Quant Imaging Med Surg 2021; 11:3792-3796. [PMID: 34341750 DOI: 10.21037/qims-20-964] [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: 08/12/2020] [Accepted: 01/18/2021] [Indexed: 11/06/2022]
Abstract
High dorsal resection (HDR) of the liver is a systematic resection technique for hepatocellular carcinoma (HCC) arising in the caudate lobe. HDR is rarely performed, as the procedure requires a high level of operative skill, knowledge of liver anatomy and is performed in patients with limited hepatic function. Between 2002 and 2012, we performed HDR on 9 patients. The median operation time was 534 min (range, 349-903 min), and the median blood loss volume was 430 mL (range, 94-4,530 mL). The severe morbidity rate was 11.1%, but there was no operative mortality, and the median hospitalization was 13 days (range, 8-93 days). The overall survival was 49.7 months (range, 3.1-89.0 months). Despite the hard-to-approach anatomic location, HDR can be carried out safely with good survival compared to other segments.
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Affiliation(s)
- Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masaru Aoki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Nao Yoshida
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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Kaibori M, Yoshii K, Kashiwabara K, Kokudo T, Hasegawa K, Izumi N, Murakami T, Kudo M, Shiina S, Sakamoto M, Nakashima O, Matsuyama Y, Eguchi S, Yamashita T, Takayama T, Kokudo N, Kubo S. Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey. Hepatol Res 2021; 51:890-901. [PMID: 34041804 DOI: 10.1111/hepr.13676] [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: 03/03/2021] [Revised: 05/13/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
AIM We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.
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Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Kengo Yoshii
- Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kosuke Kashiwabara
- Biostatistics Division, Clinical Research Support Center, Central Coordinating Unit, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takamichi Murakami
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Yutaka Matsuyama
- Department of Biostatics, School of Public Health University of Tokyo, Tokyo, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuya Yamashita
- Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings. Abdom Radiol (NY) 2021; 46:3698-3707. [PMID: 34091729 DOI: 10.1007/s00261-021-03151-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/10/2023]
Abstract
Although a small portion of patients with hepatocellular carcinoma (HCC) have radiologically evident extrahepatic disease at the initial presentation, a larger number of them develop metastatic disease later during the course of treatment or after definitive treatment. Furthermore, early metastatic disease could be overlooked by imaging due to small size and non-specificity of findings. Extrahepatic spread of HCC occurs via different pathways and is directly fueled by tumor biology and its molecular characteristics. Early and accurate detection of extrahepatic disease in patients with HCC has significant impact on management and selection of treatment options. Additionally, precise staging of disease will allow for better prediction of survival and outcome. Different pathways of regional and systemic spread of HCC with their proposed mechanisms and relevant underlying molecular derangement will be discussed in this article. Potential roles in management of patients with HCC will be discussed and reviewed in this article.
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Laohawetwanit T, Lerttanatum N, Wanpiyarat N, Manasilp N, Chaiparnich S. Combined hepatocellular-cholangiocarcinoma and its mimickers: Diagnostic pitfalls in surgical pathology. Ann Diagn Pathol 2021; 53:151770. [PMID: 34147845 DOI: 10.1016/j.anndiagpath.2021.151770] [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: 05/02/2021] [Accepted: 06/10/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND The diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) requires histomorphological detection of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, these primary liver cancers (PLCs) have a wide variety of microscopic appearances resulting in difficulties and uncertainties in cHCC-CCA's diagnosis. This study aims to perform a clinicopathologic analysis on the diagnosis of PLCs at a tertiary referral hospital in Thailand using traditional morphologic studies. METHODS A 5-year retrospective analysis of pathologically diagnosed PLCs was conducted. Pathological features and clinical characteristics of cHCC-CCA and other PLCs with the histopathologic resemblance to cHCC-CCA were studied. The pathological diagnosis was rendered based on histomorphological context rather than immunoreactivity. A literature review containing diagnostic pitfalls of cHCC-CCA was carried out. RESULTS PLCs from a total of 295 patients were retrieved, and cHCC-CCA accounted for 1.4% (n = 4) of the malignancies. Histomorphological evaluation is the most reliable diagnostic modality for cHCC-CCA. Extremely uncommon variants of iCCA (i.e., mucinous iCCA and adenosquamous iCCA) and iCCA arising with hepatocellular nodular lesions (i.e., iCCA with nodular regenerative hyperplasia (NRH), and iCCA in cirrhosis) could have a histomorphologic resemblance to that of cHCC-CCA. CONCLUSIONS Although there has been an exceedingly high incidence of iCCA in Thailand, such a commonness is not valid for cHCC-CCA in our series. Rare forms of iCCA could have a morphologic resemblance to that of cHCC-CCA. Regardless of the differentiation and immunophenotype, iCCA without a distinct HCC component should never be diagnosed as cHCC-CCA.
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Affiliation(s)
- Thiyaphat Laohawetwanit
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand; Division of Pathology, Thammasat University Hospital, Pathumthani, Thailand.
| | | | - Natcha Wanpiyarat
- Department of Pathology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Natcha Manasilp
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
| | - Sirawich Chaiparnich
- Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand
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Mähringer‐Kunz A, Meyer FI, Hahn F, Müller L, Düber C, Pinto Dos Santos D, Galle PR, Weinmann A, Kloeckner R, Schotten S. Hepatic vein tumor thrombosis in patients with hepatocellular carcinoma: Prevalence and clinical significance. United European Gastroenterol J 2021; 9:590-597. [PMID: 34077613 PMCID: PMC8259264 DOI: 10.1002/ueg2.12098] [Citation(s) in RCA: 2] [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] [Received: 11/26/2020] [Revised: 03/04/2021] [Accepted: 03/07/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND There is strong evidence that portal vein tumor thrombosis (PVTT) is associated with poor survival in patients with hepatocellular carcinoma (HCC). However, data regarding the clinical significance of hepatic vein tumor thrombosis (HVTT) is rare, particularly in Western patients. OBJECTIVE To determine the HVTT prevalence in a Western patient population and its impact on survival. METHODS We included 1310 patients with HCC treated in our tertiary referral center between January 2005 and December 2016. HVTT and PVTT were diagnosed with contrast-enhanced cross-sectional imaging. Overall survival (OS) was calculated starting from the initial HCC diagnosis, and in a second step, starting from the first appearance of vascular invasion. RESULTS We observed macrovascular invasion (MVI) in 519 patients who suffered from either isolated HVTT (n = 40), isolated PVTT (n = 352), or both combined (HVTT + PVTT) (n = 127). Calculated from the initial HCC diagnosis, the median OS for patients with isolated HVTT was significantly shorter than that of patients without MVI (13.3 vs. 32.5 months, p < 0.001). Calculated from the first appearance of MVI, the median OS was similar among patients with isolated HVTT (6.5 months), isolated PVTT (5 months), and HVTT + PVTT (5 months). Multivariate analysis confirmed HVTT as an independent risk factor for poor survival. CONCLUSIONS HVTT may be more common than typically reported. In most patients, it was accompanied by PVTT. Isolated HVTT occurred less frequently and later than isolated PVTT; however, once developed, it had the same deleterious impact on survival. Therefore, patients with HVTT should be classified as advanced stage of HCC.
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Affiliation(s)
- Aline Mähringer‐Kunz
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Franziska I. Meyer
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
- Department of RadiologyUniversity Hospital CologneCologneGermany
| | - Felix Hahn
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Lukas Müller
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Christoph Düber
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | | | - Peter R. Galle
- Department of Internal MedicineUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Arndt Weinmann
- Department of Internal MedicineUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
- Clinical Registry Unit (CRU)University Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Sebastian Schotten
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
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Kudo M. Surveillance, Diagnosis, and Treatment Outcomes of Hepatocellular Carcinoma in Japan: 2021 Update. Liver Cancer 2021; 10:167-180. [PMID: 34239807 PMCID: PMC8237798 DOI: 10.1159/000516491] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/13/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
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Chen YS, Hsieh PM, Lin HY, Hung CM, Lo GH, Hsu YC, Lu IC, Lee CY, Wu TC, Yeh JH, Hsiao P, Li YC, Wang YC, Hsieh KC, Lin CW. Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis. BMC Gastroenterol 2021; 21:220. [PMID: 33990184 PMCID: PMC8120780 DOI: 10.1186/s12876-021-01807-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/06/2021] [Indexed: 12/15/2022] Open
Abstract
Background The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.
Methods Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results
In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. Conclusions SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01807-4.
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Affiliation(s)
- Yaw-Sen Chen
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Pei-Min Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Hung-Yu Lin
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chao-Ming Hung
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - I-Cheng Lu
- Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chih-Yuan Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, 100, Taiwan, ROC
| | - Tsung-Chin Wu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Pojen Hsiao
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Yu-Chan Li
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Ya-Chin Wang
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Kun-Chou Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC. .,Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan, ROC. .,Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan, ROC.
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Mähringer-Kunz A, Steinle V, Kloeckner R, Schotten S, Hahn F, Schmidtmann I, Hinrichs JB, Düber C, Galle PR, Lang H, Weinmann A. The impact of portal vein tumor thrombosis on survival in patients with hepatocellular carcinoma treated with different therapies: A cohort study. PLoS One 2021; 16:e0249426. [PMID: 33961627 PMCID: PMC8104403 DOI: 10.1371/journal.pone.0249426] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Portal vein tumor thrombosis (PVTT) is a frequent complication of hepatocellular carcinoma (HCC), which leads to classification as advanced stage disease (regardless of the degree of PVTT) according to the Barcelona Clinic Liver Cancer Classification. For such patients, systemic therapy is the standard of care. However, in clinical reality, many patients with PVTT undergo different treatments, such as resection, transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or best supportive care (BSC). Here we examined whether patients benefited from such alternative therapies, according to the extent of PVTT. METHODS This analysis included therapy-naïve patients with HCC and PVTT treated between January 2005 and December 2016. PVTT was classified according to the Liver Cancer study group of Japan as follows: Vp1 = segmental PV invasion; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. Overall survival (OS) was analyzed for each treatment subgroup considering the extent of PVTT. We performed Cox regression analysis with adjustment for possible confounders. To further attenuate selection bias, we applied propensity score weighting using the inverse probability of treatment weights. RESULTS A total of 278 treatment-naïve patients with HCC and PVTT were included for analysis. The median observed OS in months for each treatment modality (resection, TACE/SIRT, sorafenib, BSC, respectively) was 32.4, 8.1, N/A, and 1.7 for Vp1; 10.7, 6.9, 5.5, and 1.2 for Vp2; 6.6, 7.5, 2.9, and 0.6 for Vp3; and 8.0, 3.6, 5.3, and 0.7 for Vp4. Thus, the median OS in the resection group in case of segmental PVTT (Vp1) was significantly longer compared to any other treatment group (all p values <0.01). CONCLUSIONS Treatment strategy for HCC with PVTT should not be limited to systemic therapy in general. The extent of PVTT should be considered when deciding on treatment alternatives. In patients with segmental PVTT (Vp1), resection should be evaluated.
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Affiliation(s)
- Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Verena Steinle
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
- Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Sebastian Schotten
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, HSK Wiesbaden, Germany
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Irene Schmidtmann
- Department of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg University Mainz, Mainz, Germany
| | | | - Christoph Düber
- Department of Diagnostic and Interventional Radiology, University Medical Center Mainz, Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center Mainz, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
- Clinical Registry Unit (CRU), University Medical Center Mainz, Mainz, Germany
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36
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A resected case of ruptured peritoneal metastasis of hepatocellular carcinoma. Clin J Gastroenterol 2021; 14:1240-1243. [PMID: 33895971 DOI: 10.1007/s12328-021-01414-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 04/13/2021] [Indexed: 10/21/2022]
Abstract
Peritoneal metastases of hepatocellular carcinoma (HCC) are occasionally observed, but rupture of such metastases is rare. We report a resected case with a single ruptured peritoneal HCC metastasis. A 57-year-old man with chronic hepatitis C underwent hepatic resection twice for hepatocellular carcinoma. Recurrence in S3 was found, and the tumor was treated by radiofrequency ablation therapy (RFA). One month after RFA, plane computed tomography (CT) showed a nodule with a diameter of 5 cm near the upper pole of the spleen, and the serum alpha-fetoprotein (AFP) level remained high. The patient was admitted to hospital, with a chief complaint of abdominal pain 4 days after the CT scan, and diagnosed with intra-abdominal hemorrhage caused by a ruptured peritoneal HCC metastatic nodule. We performed semi-urgent surgery, including splenectomy and peritoneal metastasis resection, and the patient was discharged on the 10th postoperative day. Histopathological examination of the nodule confirmed HCC metastasis. The patient is alive with no evidence of recurrence as of 1 year and 6 months after the operation, with AFP levels remaining within the normal range.
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Matsumoto N, Ogawa M, Kaneko M, Kumagawa M, Watanabe Y, Hirayama M, Nakagawara H, Masuzaki R, Kanda T, Moriyama M, Takayama T, Sugitani M. Quantitative Ultrasound Image Analysis Helps in the Differentiation of Hepatocellular Carcinoma (HCC) From Borderline Lesions and Predicting the Histologic Grade of HCC and Microvascular Invasion. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:689-698. [PMID: 32840896 DOI: 10.1002/jum.15439] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/29/2020] [Accepted: 07/04/2020] [Indexed: 05/14/2023]
Abstract
OBJECTIVES Quantitative image analysis is one of the methods to overcome the lack of objectivity of ultrasound (US). The aim of this study was to clarify the correlation between the features from a US image analysis and the histologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and differentiation of HCC smaller than 2 cm from borderline lesions. METHODS We retrospectively analyzed grayscale US images with histopathologic evidence of HCC or a precancerous lesion using ImageJ version 1.47 software (National Institutes of Health, Bethesda, MD). RESULTS A total of 148 nodules were included (borderline lesion, n = 31; early HCC [eHCC], n = 3; well-differentiated HCC [wHCC], n = 16; moderately differentiated HCC [mHCC], n = 79; and poorly differentiated HCC [pHCC], n = 19). A multivariate analysis selected lower minimum gray values (odds ratio [OR], 0.431; P = .003) and a higher standard deviation (OR, 1.880; P = .019) as predictors of HCC smaller than 2 cm. Median (range) minimum gray values of borderline lesions, eHCC, wHCC, mHCC, and pHCC were 29 (0-103), 7 (0-47), 6 (0-60), 10 (0-53), and 2 (0-38), respectively, and gradually decreased from borderline lesions to pHCC (P < 0.001). The multivariate analysis showed a higher aspect ratio (OR, 2.170; P = .001) and lower minimum gray value (OR, 0.475; P = .043) as predictors of MVI. An anechoic area diagnosed by a subjective evaluation was correlated with the minimum gray value (P < .0001). The proportion of the anechoic area gradually increased from eHCC to pHCC (P = .031). CONCLUSIONS In a US image analysis, HCC smaller than 2 cm had features of greater heterogeneity and a lower minimum gray value than borderline lesions. Moderately differentiated HCC was smoother than borderline lesions, and the anechoic area correlated with histologic grading. Microvascular invasion was correlated with a slender shape and a lower minimum gray value.
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Affiliation(s)
- Naoki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiro Ogawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiro Kaneko
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Mariko Kumagawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Yukinobu Watanabe
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Midori Hirayama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hiroshi Nakagawara
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ryota Masuzaki
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiko Sugitani
- Department of Pathology, Nihon University School of Medicine, Tokyo, Japan
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38
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Kudo M, Izumi N, Kokudo N, Sakamoto M, Shiina S, Takayama T, Tateishi R, Nakashima O, Murakami T, Matsuyama Y, Takahashi A, Miyata H, Kubo S. Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011). Hepatol Res 2021; 51:355-405. [PMID: 33382910 DOI: 10.1111/hepr.13612] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/01/2020] [Accepted: 12/13/2020] [Indexed: 12/11/2022]
Abstract
In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.
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Affiliation(s)
- Masatoshi Kudo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Namiki Izumi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Norihiro Kokudo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takamichi Murakami
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Arata Takahashi
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,National Clinical Database, Tokyo, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shoji Kubo
- Follow-up Survey Committee, Liver Cancer Study Group of Japan, Osaka-Sayama, Japan.,Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Shirono T, Niizeki T, Iwamoto H, Shimose S, Suzuki H, Kawaguchi T, Kamachi N, Noda Y, Okamura S, Nakano M, Kuromatu R, Koga H, Torimura T. Therapeutic Outcomes and Prognostic Factors of Unresectable Intrahepatic Cholangiocarcinoma: A Data Mining Analysis. J Clin Med 2021; 10:jcm10050987. [PMID: 33801202 PMCID: PMC7957874 DOI: 10.3390/jcm10050987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/15/2022] Open
Abstract
Prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is unsatisfactory. Tumor, host, and treatment factors including hepatic arterial infusion chemotherapy (HAIC) are intricately involved in the progression of ICC. We aimed to identify profiles associated with disease control rate (DCR) and the prognosis of patients with unresectable ICC by decision tree analysis. We analyzed 31 consecutive patients with unresectable ICC (median age, 71 years; the male ratio was 58.1%). Stage IVB occupied 51.6% of patients, and 38.7% and 58.1% of patients were treated with gemcitabine plus cisplatin combination therapy and HAIC, respectively. Profiles associated with prognosis as well as DCR were investigated by decision tree analysis. The median survival time (MST) of the patients was 11.6 months, and the DCR was 70.9%. Multivariate correlation analysis showed that albumin levels and WBC levels were significantly correlated with survival time (albumin, ρ = 0.3572, p = 0.0485; WBC, ρ = -0.4008, p = 0.0280). In decision tree analysis, WBC level was selected as the initial split variable, and subjects with WBC levels of 6800/μL or less (45.1%) showed a long survival time (MST 476 days). We also demonstrated that the profile associated with the highest DCR was "less than 4.46 mg/dL of CRP levels and treatment with HAIC". We demonstrated a new prognostic profile for ICC patients, which consisted of WBC and CRP levels. Moreover, we demonstrated that HAIC was associated with better disease control in ICC patients with low CPR levels. Thus, these new profiles may be useful for the management of ICC patients.
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40
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Fukuyoshi J, Korenaga M, Yoshii Y, Hong L, Kashihara S, Sigel B, Takebayashi T. Increasing hepatitis virus screening uptake at worksites in Japan using nudge theory and full subsidies. Environ Health Prev Med 2021; 26:18. [PMID: 33522902 PMCID: PMC7849075 DOI: 10.1186/s12199-021-00940-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 01/19/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Despite the importance of hepatitis screening for decreasing liver cancer mortality, screening rates remain low in Japan. Previous studies show that full subsidies increase screening uptake, but full subsidies are costly and difficult to implement in low-resource settings. Alternatively, applying nudge theory to the message design could increase screening at lower costs. This study examined the effects of both methods in increasing hepatitis virus screening rates at worksites. METHODS 1496 employees from a Japanese transportation company received client reminders for an optional hepatitis virus screening before their general health checkups. Groups A and B received a client reminder designed based on the principles of "Easy" and "Attractive," while the control group received a client reminder not developed using nudge theory. Additionally, hepatitis virus screening was offered to the control group and group A for a co-payment of JPY 612, but was fully subsidized for group B. The hepatitis virus screening rates among the groups were compared using a Chi-square test with Bonferroni correction, and the risk ratios of group A and group B to the control group were also calculated. To adjust for unobservable heterogeneity per cluster, the regression analysis was performed using generalized linear mixed models. RESULTS The screening rate was 21.2%, 37.1%, and 86.3% for the control group, group A, and group B, respectively. And the risk ratio for group A was 1.75 (95% confidence interval [CI] 1.45-2.12) and that of group B was 4.08 (95% CI 3.44-4.83). The parameters of group A and group B also were significant when estimated using generalized linear mixed models. However, the cost-effectiveness (incremental cost-effectiveness ratio (ICER)) of the nudge-based reminder with the full subsidies was lower than that of only the nudge-based reminder. CONCLUSIONS While fully subsidized screening led to the highest hepatitis screening rates, modifying client reminders using nudge theory significantly increased hepatitis screening uptake at lower costs per person.
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Affiliation(s)
- Jun Fukuyoshi
- Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Shinanomachi, Tokyo, 160-8582 Japan
| | - Masaaki Korenaga
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, 272-8516 Japan
| | - Yui Yoshii
- Department of Social and Preventive Epidemiology, School of Public Health, Graduate School of Medicine, Tokyo University, Hongo, Tokyo, 113-0033 Japan
| | - Lek Hong
- Department of Policy Management, Keio University, Fujisawa, Kanagawa 252-0882 Japan
| | | | - Byron Sigel
- School of International Health, Graduate School of Medicine, Tokyo University, Hongo, Tokyo, 113-0033 Japan
| | - Toru Takebayashi
- Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Shinanomachi, Tokyo, 160-8582 Japan
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41
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Chiu SH, Chang PY, Shih YL, Huang WY, Ko KH, Chang WC, Huang GS. Efficacy and Safety of Supplemental Transarterial Chemoembolization Through Extrahepatic Collateral Arteries with Drug-eluting Beads: Treatment for Unresectable Hepatocellular Carcinoma. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:5029-5041. [PMID: 33235441 PMCID: PMC7680099 DOI: 10.2147/dddt.s266470] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/08/2020] [Indexed: 12/20/2022]
Abstract
Purpose To evaluate the therapeutic efficacy and safety of supplement transarterial chemoembolization (TACE) with drug-eluting beads TACE (DEB-TACE) through extrahepatic collateral (EHC) arteries for the treatment of hepatocellular carcinoma (HCC). Patients and Methods In this retrospective study, 61 unresectable HCC patients with treatment-naïve EHC blood supplies who received TACE from January 2016 to March 2019 were enrolled; of these patients, 42 (68.9%) received DEB-TACE, and 19 (31.1%) received cTACE. The hepatic tumor feeding arteries were treated in the same TACE session if it presented. The tumor response, time-to-progression (TTP), and overall survival (OS) were analyzed. Safety was assessed based on the occurrence of liver function deterioration and major complications within three months after TACE. Results DEB-TACE showed better efficacy than cTACE in the disease control rate (p=0.001), overall response rate (p=0.005), the TTP (eight months vsthree months, p=0.002) and the OS (23.8 months vs nine months, p=0.045). Nine patients in the DEB-TACE group and one patient in the cTACE group were downstaged to resection or liver transplantation (21.4% vs 5.3%, p=0.151). DEB-TACE and cTACE have no difference in the acute and chronic liver toxicity. With regard to complications, there was no significant difference in the occurrence of both major (16.7% vs 21.1%, p=0.72) and minor (57.1% vs 47.4%, p=0.48) complications between DEB-TACE and cTACE. Conclusion DEB-TACE through EHC arteries has a potential therapeutic effect in the treatment of unresectable HCC, with comparable safety compared with cTACE.
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Affiliation(s)
- Sung-Hua Chiu
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ping-Ying Chang
- Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Yen Huang
- Department of Radiotherapy, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Kai-Hsiung Ko
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Guo-Shu Huang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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42
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Onozuka D, Nakamura Y, Tsuji G, Furue M. Mortality in Yusho patients exposed to polychlorinated biphenyls and polychlorinated dibenzofurans: a 50-year retrospective cohort study. Environ Health 2020; 19:119. [PMID: 33228703 PMCID: PMC7685647 DOI: 10.1186/s12940-020-00680-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 11/17/2020] [Indexed: 05/03/2023]
Abstract
BACKGROUND In 1968, the Yusho incident resulted in accidental exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related compounds in Japan. This study updated the risk of mortality in Yusho patients. METHODS We obtained updated cohort data for all Yusho patients for the period 1968-2017. We calculated standardized mortality ratios (SMRs) for all-cause and cause-specific mortality over a 50-year follow-up period compared with the general population in Japan. RESULTS A total of 1664 Yusho patients with 63,566 person-years of follow up were included in the analysis. Among males, excess mortality was observed for all cancers (SMR: 1.22, 95% confidence interval [CI]: 1.02 to 1.45) and lung cancer (SMR: 1.59, 95% CI: 1.12 to 2.19). Among females, increased mortality was observed for liver cancer (SMR: 2.05, 95% CI: 1.02 to 3.67). No significant increase was seen in non-cancer-related mortality compared with the general population. CONCLUSIONS Carcinogenic risk in humans after exposure to PCBs and PCDFs remains higher among Yusho patients. Our findings suggest the importance of care engagement and optimum management to deal with the burden of Yusho disease.
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Affiliation(s)
- Daisuke Onozuka
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibeshin-machi, Suita, Osaka, 564-8565 Japan
- Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuko Nakamura
- Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, Japan
| | - Gaku Tsuji
- Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, Japan
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masutaka Furue
- Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, Japan
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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43
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Aiyama T, Orimo T, Yokoo H, Ohata T, Hatanaka KC, Hatanaka Y, Fukai M, Kamiyama T, Taketomi A. Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis. PLoS One 2020; 15:e0239462. [PMID: 32956413 PMCID: PMC7505586 DOI: 10.1371/journal.pone.0239462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 09/08/2020] [Indexed: 02/05/2023] Open
Abstract
This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.
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MESH Headings
- Adult
- Aged
- Animals
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Cell Differentiation
- Cell Line, Tumor
- Cell Proliferation
- Female
- Gene Expression Regulation, Neoplastic
- Gene Knockout Techniques
- Genes, APC
- Hepatitis, Viral, Human/complications
- Heterografts
- Humans
- Kaplan-Meier Estimate
- Liver Neoplasms/complications
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- Male
- Mice, Inbred BALB C
- Mice, Nude
- Microtubule-Associated Proteins/antagonists & inhibitors
- Microtubule-Associated Proteins/genetics
- Microtubule-Associated Proteins/physiology
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Neoplasm Proteins/antagonists & inhibitors
- Neoplasm Proteins/genetics
- Neoplasm Proteins/physiology
- Portal Vein/pathology
- Prognosis
- RNA Interference
- RNA, Messenger/biosynthesis
- RNA, Messenger/genetics
- RNA, Neoplasm/biosynthesis
- RNA, Neoplasm/genetics
- RNA, Small Interfering/genetics
- Recombinant Proteins/metabolism
- Recurrence
- Survival Rate
- Tissue Array Analysis
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Affiliation(s)
- Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Takanori Ohata
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Kanako C. Hatanaka
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Yutaka Hatanaka
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Moto Fukai
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
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Ueshima K, Ogasawara S, Ikeda M, Yasui Y, Terashima T, Yamashita T, Obi S, Sato S, Aikata H, Ohmura T, Kuroda H, Ohki T, Nagashima K, Ooka Y, Takita M, Kurosaki M, Chayama K, Kaneko S, Izumi N, Kato N, Kudo M, Omata M. Hepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Liver Cancer 2020; 9:583-595. [PMID: 33083282 PMCID: PMC7548914 DOI: 10.1159/000508724] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 05/15/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM). METHODS The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM. RESULTS Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475-0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699-2.155; p = 0.475). CONCLUSION HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.
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Affiliation(s)
- Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan,Translational Research and Development Center, Chiba University Hospital, Chiba, Japan,*Sadahisa Ogasawara, Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan),
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Takeshi Terashima
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan,Advanced Preventive Medical Sciences Research Center, Kanazawa University, Kanazawa, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan,Advanced Preventive Medical Sciences Research Center, Kanazawa University, Kanazawa, Japan
| | - Shuntaro Obi
- Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara, Japan,Department of Gastroenterology and Hepatology, Kyoundo Hospital of the Sasaki Institute, Tokyo, Japan
| | - Shinpei Sato
- Department of Gastroenterology and Hepatology, Kyoundo Hospital of the Sasaki Institute, Tokyo, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Takumi Ohmura
- Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Takamasa Ohki
- Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Kengo Nagashima
- Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
| | - Yoshihiko Ooka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masahiro Takita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan,Translational Research and Development Center, Chiba University Hospital, Chiba, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, Kofu, Japan,The University of Tokyo, Tokyo, Japan
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Chi Q, Shi Z, Zhang Z, Zhang X, Zhang L, Weng S. Outcomes of resection for hepatocellular carcinoma with macroscopic bile duct tumour thrombus: A propensity score matched study. Oncol Lett 2020; 20:118. [PMID: 32863931 PMCID: PMC7448567 DOI: 10.3892/ol.2020.11979] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 07/13/2020] [Indexed: 12/14/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is low, and related studies, especially studies on long-term survival, are uncommon. The present study aimed to evaluate the clinicopathological characteristics, prognostic factors and postoperative long-term outcomes of BDTT in patients with HCC. The clinicopathological characteristics and postoperative long-term outcomes of patients with HCC both with and without BDTT were compared before and after propensity score matching (PSM). Prognostic risk factors were assessed by Cox proportional hazards regression analyses after PSM. Tumour stages in the BDTT group were significantly higher than those in the group without BDTT (P=0.001). Overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher in the group without BDTT than in the BDTT group before PSM (P<0.001 and P=0.003, respectively). However, no significant difference in OS or RFS was found between the two groups after PSM (P=0.249 and P=0.121, respectively). Moreover, the median OS and RFS times of the BDTT patients who underwent tumour thrombectomy and bile duct resection were not significantly different (P=0.891 and P=0.787, respectively). In the multivariate analysis, macrovascular invasion (HR, 3.701; 95% CI, 1.313-9.10.437; P=0.013) was the only independent predictor of OS. Although the clinicopathological characteristics of the BDTT group suggested more advanced stage disease and poorer oncological outcomes than the group without BDTT, BDTT was not a poor prognostic factor for patients with HCC who underwent liver resection. Curative resection is recommended for patients with HCC and BDTT, even for those with poor liver function, after proper perioperative management in order to achieve good long-term survival.
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Affiliation(s)
- Qiyu Chi
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Zheng Shi
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Zhibo Zhang
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Xiang Zhang
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Li Zhang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Shangeng Weng
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
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Iida H, Tani M, Aihara T, Hasegawa K, Eguchi H, Tanabe M, Yamamoto M, Yamaue H. New metastasectomy criteria for peritoneal metastasis of hepatocellular carcinoma: A study of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:673-681. [DOI: 10.1002/jhbp.796] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 06/19/2020] [Accepted: 06/23/2020] [Indexed: 12/22/2022]
Affiliation(s)
- Hiroya Iida
- Department of Surgery Shiga University of Medical Science Otsu Japan
| | - Masaji Tani
- Department of Surgery Shiga University of Medical Science Otsu Japan
| | | | - Kiyoshi Hasegawa
- Hepato‐Biliary‐Pancreatic Surgery Division Department of Surgery Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery Graduate School of Medicine Osaka University Osaka Japan
| | - Minoru Tanabe
- Department of Hepato‐Biliary‐Pancreatic Surgery Tokyo Medical and Dental University Tokyo Japan
| | - Masakazu Yamamoto
- Department of Surgery Institute of Gastroenterology Tokyo Women’s Medical University Tokyo Japan
| | - Hiroki Yamaue
- Second Department of Surgery Wakayama Medical University Wakayama Japan
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47
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Itano O, Takemura Y, Kishida N, Tamagawa E, Shinozaki H, Ikeda K, Urakami H, Ei S, Hayatsu S, Suzuki K, Sakuragawa T, Ishii M, Shito M, Aiura K, Fujisaki H, Takano K, Matsui J, Minagawa T, Shinoda M, Kitago M, Abe Y, Yagi H, Oshima G, Hori S, Kitagawa Y. A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01). BMC Cancer 2020; 20:688. [PMID: 32703191 PMCID: PMC7379785 DOI: 10.1186/s12885-020-07185-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 07/15/2020] [Indexed: 12/21/2022] Open
Abstract
Background Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. Methods The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1–28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). Results Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. Conclusions One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. Trial registration UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347
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Affiliation(s)
- Osamu Itano
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan. .,Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, 4-3, Kozunomori, Narita-shi, Chiba, 286-8686, Japan.
| | - Yusuke Takemura
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Norihiro Kishida
- Department of Surgery, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan
| | - Eiji Tamagawa
- Department of Surgery, Machida Keisen Hospital, Tokyo, Japan
| | | | - Ken Ikeda
- Department of Surgery, Sano Kousei General Hospital, Tochigi, Japan
| | - Hidejiro Urakami
- Department of Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Shigenori Ei
- Department of Surgery, Eiju General Hospital, Tokyo, Japan
| | - Shigeo Hayatsu
- Department of Surgery, National Hospital Organization Saitama National Hospital, Saitama, Japan
| | - Keiichi Suzuki
- Department of Surgery, National Hospital Organization Tochigi Medical Center, Tochigi, Japan
| | | | | | - Masaya Shito
- Department of Surgery, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan
| | - Koichi Aiura
- Department of Surgery, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan
| | - Hiroto Fujisaki
- Department of Surgery, Hiratsuka City Hospital, Kanagawa, Japan
| | - Kiminori Takano
- Department of Surgery, Hiratsuka City Hospital, Kanagawa, Japan
| | - Junichi Matsui
- Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan
| | - Takuya Minagawa
- Department of Surgery, Saitama City Hospital, Saitama, Japan
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Go Oshima
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Liu W, Xu H, Ying X, Zhang D, Lai L, Wang L, Tu J, Ji J. Radiofrequency Ablation (RFA) Combined with Transcatheter Arterial Chemoembolization (TACE) for Patients with Medium-to-Large Hepatocellular Carcinoma: A Retrospective Analysis of Long-Term Outcome. Med Sci Monit 2020; 26:e923263. [PMID: 32667906 PMCID: PMC7382301 DOI: 10.12659/msm.923263] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the prognostic value of radiofrequency ablation (RFA) plus transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with tumor size ranging from 3.0 to 10.0 cm. MATERIAL AND METHODS We retrospectively analyzed data on 201 patients with medium-to-large HCC. According to treatment procedure, the patients were divided into the TACE group (n=124) and the TACE+RFA group (n=77). We recorded data on patient safety, subcapsular hepatic hematoma, large amount of ascites, liver abscess, gallbladder injury, and local skin infection. The overall survival (OS) and progression-free survival (PFS) in the 2 groups were analyzed and compared between groups. RESULTS The median PFS was 4.00 months (3.00-5.00 months) in the TACE group and 9.13 months (6.64-11.62 months) in the TACE+RFA group (P<0.001). Median OS was 12.00 months (8.88-15.13 months) in the TACE group and 27.57 months (20.06-35.08 months) in the TACE+RFA group (P<0.001). In the TACE+RFA group, multivariate Cox regression analysis showed that tumor size ≤5 cm) (HR: 1.952, 95% CI: 1.213-3.143, P=0.006), hepatitis B (HR: 2.323, 95% CI: 1.096-4.923, P=0.028), TACE times (1 or >1) (HR: 1.867, 95% CI: 1.156-3.013, P=0.011), alpha-fetoprotein (AFP) level >200 ng/ml (HR: 2.426, 95% CI: 1.533-3.839, P<0.001), and AST level >40 U/L (HR: 1.946, 95% CI: 1.196-3.166, P=0.007) were independent prognostic factors for overall survival. CONCLUSIONS Combination therapy of TACE with RFA is a safe and effective treatment for patients with medium-to-large HCC, with the long-term beneficial effect of retarding tumor progression and improving PFS and OS.
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Affiliation(s)
- Weiwen Liu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Huihong Xu
- Department of Radiology, Qingtian County People's Hospital of Lishui City, Lishui, Zhejiang, China (mainland)
| | - Xihui Ying
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Dengke Zhang
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Linqiang Lai
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Linyou Wang
- Department of Radiology, Taizhou Municipal Hospital of Zhejiang Province, Taizhou, Zhejiang, China (mainland)
| | - Jianfei Tu
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
| | - Jiansong Ji
- Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang, Lishui, Zhejiang, China (mainland)
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Ichikawa S, Isoda H, Shimizu T, Tamada D, Taura K, Togashi K, Onishi H, Motosugi U. Distinguishing intrahepatic mass-forming biliary carcinomas from hepatocellular carcinoma by computed tomography and magnetic resonance imaging using the Bayesian method: a bi-center study. Eur Radiol 2020; 30:5992-6002. [PMID: 32500195 DOI: 10.1007/s00330-020-06972-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/07/2020] [Accepted: 05/20/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To determine imaging hallmarks for distinguishing intrahepatic mass-forming biliary carcinomas (IMBCs) from hepatocellular carcinoma (HCC) and to validate their diagnostic ability using Bayesian statistics. METHODS Study 1 retrospectively identified clinical and imaging hallmarks that distinguish IMBCs (n = 41) from HCC (n = 247) using computed tomography (CT) and magnetic resonance imaging (MRI). Study 2 retrospectively assessed the diagnostic ability of these hallmarks to distinguish IMBCs (n = 37) from HCC (n = 111) using Bayesian statistics with images obtained from a different institution. We also assessed the diagnostic ability of the hallmarks in the patient subgroup with high diagnostic confidence (≥ 80% of post-test probability). Two radiologists independently evaluated the imaging findings in studies 1 and 2. RESULTS In study 1, arterial phase peritumoral parenchymal enhancement on CT/MRI, delayed enhancement on CT/MRI, diffusion-weighted imaging peripheral hyperintensity, and bile duct dilatation were hallmarks indicating IMBCs, whereas chronic liver disease, non-rim arterial phase hyperenhancement on CT/MRI, enhancing capsule on CT/MRI, and opposed-phase signal drop were hallmarks indicating HCC (p = 0.001-0.04). In study 2, Bayesian statistics-based post-test probability combining all hallmark features had a diagnostic accuracy of 89.2% (132/148) in distinguishing IMBCs from HCC for both readers. In the high diagnostic confidence subgroup (n = 120 and n = 124 for readers 1 and 2, respectively), the accuracy improved (95.0% (114/120) and 93.5% (116/124) for readers 1 and 2, respectively). CONCLUSIONS Combined interpretation of CT and MRI to identify hallmark features is useful in discriminating IMBCs from HCCs. High post-test probability by Bayesian statistics allows for a more reliable non-invasive diagnosis. KEY POINTS • Combined interpretation of CT and MRI to identify hallmark features was useful in discriminating intrahepatic mass-forming biliary carcinomas from hepatocellular carcinoma. • Bayesian method-based post-test probability combining all hallmark features determined in study 1 showed high (> 90%) sensitivity and specificity for distinguishing intrahepatic mass-forming biliary carcinomas from hepatocellular carcinoma. • If the post-test probability or the confidence was ≥ 80% when combining the imaging features of CT and MRI, the high specificity of > 95% was achieved without any loss of sensitivity to distinguish hepatocellular carcinoma from intrahepatic mass-forming biliary carcinomas.
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Affiliation(s)
- Shintaro Ichikawa
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan.
| | - Hiroyoshi Isoda
- Preemptive Medicine and Lifestyle-related Disease Research Center, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Tatsuya Shimizu
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan
| | - Daiki Tamada
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Division Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kaori Togashi
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hiroshi Onishi
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan
| | - Utaroh Motosugi
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan
- Department of Diagnostic Radiology, Kofu Kyoritsu Hospital, 1-9-1 Takara, Kofu-shi, Yamanashi, 400-0034, Japan
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Hung KC, Yang KL, Huang GC, Chen YF, Chang WT, Chuang CC. Cytoreduction surgery and hyperthermic intraperitoneal chemotherapy for treating advanced peritoneal metastases of hepatocellular carcinoma. Pleura Peritoneum 2020; 5:20190030. [PMID: 32566724 PMCID: PMC7292233 DOI: 10.1515/pp-2019-0030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 03/03/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND An effective treatment strategy for peritoneal metastasis (PM) of hepatocellular carcinoma (HCC-PM) has yet to be established. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown favorable outcomes in certain malignancies, their role in peritoneal metastatic HCC is unclear. Herein, we present a series of patients with HCC-PM treated with CRS/HIPEC and evaluate their outcomes. METHODS Records of patients with HCC-PM who had undergone CRS/HIPEC at the Hyperthermia Center of Yuan's General Hospital, Kaohsiung, Taiwan, between September 2015 and December 2016 were reviewed retrospectively. Patients were followed up until September 2019. We assessed the clinical courses and outcomes of these patients to clarify the benefits of CRS/HIPEC. RESULTS Six patients were included in our study. HCC-PM occurred synchronously in one patient and occurred metachronously in five patients after therapeutic minimally invasive procedures, including radiofrequency ablation, laparoscopic hepatectomy, robotic hepatectomy or spontaneously. The median peritoneal cancer index was 18.5. All patients experienced complete peritoneal cytoreduction without perioperative mortality. One patient had two CTCAE grade 3 complications. The median follow-up was 16 months. The median overall survival was 15.7 months. Four patients died of lung metastasis or liver failure owing to intrahepatic recurrence. The survival rates observed at 1, 2, and 4 years were 66.7%, 33.3%, and 33.3%, respectively. CONCLUSIONS CRS followed by HIPEC is feasible in patients with HCC-PM and might provide selected patients a chance for local disease control and longer survival. CRS/HIPEC might be considered as a treatment option in highly selected patients, as part of multimodal therapy approaches.
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Affiliation(s)
- Kuo-Chen Hung
- Department of Trauma Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University and College of Medicine, Kaohsiung83301, Taiwan
- Hyperthermic Center, Department of Surgery, Yuan’s General Hospital, Kaohsiung802793, Taiwan
| | - Kun-Lin Yang
- Department of Animal Science, National Peimen Agriculture and Industrial school, Tainan, Taiwan
| | - Guan-Cheng Huang
- Division of Hemato-oncology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan
| | - Yu-Fu Chen
- Department of Education and Research, Yuan’s General Hospital, Kaohsiung, Taiwan
| | - Wen-Teng Chang
- Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Chia-Chang Chuang
- Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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