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Ruff SM, Cloyd JM, Pawlik TM. Annals of Surgical Oncology Practice Guidelines Series: Management of Primary Liver and Biliary Tract Cancers. Ann Surg Oncol 2023; 30:7935-7949. [PMID: 37691030 DOI: 10.1245/s10434-023-14255-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 08/22/2023] [Indexed: 09/12/2023]
Abstract
Primary cancers of the liver and biliary tract are rare and aggressive tumors that often present with locally advanced or metastatic disease. For patients with localized disease amenable to resection, surgery typically offers the best chance at curative-intent therapy. Unfortunately, the incidence of recurrence even after curative-intent surgery remains high. In turn, patients with hepatobiliary cancers commonly require multimodality therapy including a combination of resection, systemic therapy (i.e., targeted therapy, cytotoxic chemotherapy, immunotherapy), and/or loco-regional therapies. With advancements in the field, it is crucial for surgical oncologists to remain updated on the latest guidelines and recommendations for surgical management and optimal patient selection. Given the complex and evolving nature of treatment, this report highlights the latest practice guidelines for the surgical management of hepatobiliary cancers.
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Affiliation(s)
- Samantha M Ruff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Liu YW, Li WF, Kuo FY, Eng HL, Wang CC, Lin CC, Yong CC, Yen YH. Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8 th American Joint Commission on Cancer. Langenbecks Arch Surg 2023; 408:166. [PMID: 37103595 DOI: 10.1007/s00423-023-02841-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 02/13/2023] [Indexed: 04/28/2023]
Abstract
PURPOSE The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. METHODS We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. RESULTS This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). CONCLUSION No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.
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Affiliation(s)
- Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hock-Liew Eng
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Perisetti A, Goyal H, Yendala R, Thandassery RB, Giorgakis E. Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements. World J Gastroenterol 2021; 27:3466-3482. [PMID: 34239263 PMCID: PMC8240056 DOI: 10.3748/wjg.v27.i24.3466] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/13/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.
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Affiliation(s)
- Abhilash Perisetti
- Department of Internal Medicine, Division of Gastroenterology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Hemant Goyal
- Department of Internal Medicine, Macon University School of Medicine, Macon, GA 31207, United States
| | - Rachana Yendala
- Department of Hematology and Oncology, Conway Regional Health System (CRHS), Conway, AR 72034, United States
| | - Ragesh B Thandassery
- Department of Gastroenterology and Hepatology, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, United States
| | - Emmanouil Giorgakis
- Department of Transplant, University of Arkansas for Medical Sciences Little Rock, AR 72205, United States
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 539] [Impact Index Per Article: 134.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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Wagle P, Narkhede R, Desai G, Pande P, Kulkarni DR, Varty P. SURGICAL MANAGEMENT OF LARGE HEPATOCELLULAR CARCINOMA: THE FIRST SINGLE-CENTER STUDY FROM WESTERN INDIA. ACTA ACUST UNITED AC 2020; 33:e1505. [PMID: 33237158 PMCID: PMC7682151 DOI: 10.1590/0102-672020190001e1505] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 01/21/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Majority of patients with large size HCC (>10 cm) are not offered surgery as per Barcelona Clinic Liver Cancer (BCLC) criteria and hence, their outcomes are not well studied, especially from India, owing to a lower incidence. AIM To analyze outcomes of surgery for large HCCs. METHODS This retrospective observational study included all patients who underwent surgery for large HCC from January 2007 to December 2017. The entire perioperative and follow up data was collected and analyzed. RESULTS Nineteen patients were included. Ten were non-cirrhotic; 16 were BCLC grade A; one BCLC grade B; and two were BCLC C. Two cirrhotic and three non-cirrhotic underwent preoperative sequential trans-arterial chemoembolization and portal vein embolization. Right hepatectomy was the most commonly done procedure. The postoperative 30-day mortality rate was 5% (1/19). Wound infection and postoperative ascites was seen in seven patients each. Postoperative liver failure was seen in five. Two cirrhotic and two non-cirrhotic patients had postoperative bile leak. The hospital stay was 11.9±5.4 days (median 12 days). Vascular invasion was present in four cirrhotic and five non-cirrhotic patients. The median follow-up was 32 months. Five patients died in the follow-up period. Seven had recurrence and median recurrence free survival was 18 months. The cumulative recurrence free survival was 88% and 54%, whereas the cumulative overall survival was 94% and 73% at one and three years respectively. Both were better in non-cirrhotic; however, the difference was not statistically significant. The recurrence free survival was better in patients without vascular invasion and the difference was statistically significant (p=0.011). CONCLUSION Large HCC is not a contraindication for surgery. Vascular invasion if present, adversely affects survival. Proper case selection can provide the most favorable survival with minimal morbidity.
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Affiliation(s)
- Prasad Wagle
- Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (West), Mumbai-400050, India
| | - Rajvilas Narkhede
- Balabhai Nanavati Superspeciality Hospital, Mumbai, Maharashtra- 400056, India
| | - Gunjan Desai
- Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (West), Mumbai-400050, India
| | - Prasad Pande
- Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (West), Mumbai-400050, India
| | - D R Kulkarni
- Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (West), Mumbai-400050, India
| | - Paresh Varty
- Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (West), Mumbai-400050, India
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6
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Long-term survival after partial hepatectomy for sub-stage patients with intermediate stage hepatocellular carcinoma. Int J Surg 2018; 56:256-263. [PMID: 29935368 DOI: 10.1016/j.ijsu.2018.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 04/12/2018] [Accepted: 06/14/2018] [Indexed: 02/06/2023]
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Immunohistochemical Coexpression of Epithelial Cell Adhesion Molecule and Alpha-Fetoprotein in Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2018; 2018:5970852. [PMID: 30112355 PMCID: PMC6077358 DOI: 10.1155/2018/5970852] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 07/05/2018] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND AND AIM The epithelial cell adhesion molecule (EpCAM) has been proposed as a marker for cancer stem cells in human hepatocellular carcinoma (HCC) as well as in the development of novel target therapies. This study aimed to investigate the immunohistochemical expression of EpCAM and alpha-fetoprotein (AFP) in HCC patients and their association with clinicopathological characteristics. METHODS This study included Child-Pugh A HCC patients undergoing curative surgical resection. RESULTS A significant difference was observed in the ratio between the different phenotypes (p = 0.002), identifying 12 (29.3%) EPCAM positive tumors and 29 (70.7%) negative tumors. EpCAM+ expression was associated with AFP + (OR = 12.5, 95% CI, 1.9-84.1, p<0.001). In univariate analysis, a significant association was observed between AFP+ and EPCAM+ and the serum AFP level. A diameter of ≤ 5 cm was associated with EPCAM+, while angiolymphatic invasion was associated with APF+. In a multivariate analysis, only tumors of ≤ 5 cm were significantly associated with EpCAM+ (OR = 8.7; 95%CI, 1.27-100.0; p = 0.022). The overall survival rate was 74.9%, 69.4%, 69.4%, and 53.5% at 12, 24, 36, and 48 months, respectively. CONCLUSION A considerable number of patients with EpCAM+ HCC would benefit from a specific target therapy.
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8
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Koh YX, Tan HL, Lye WK, Kam JH, Chiow AKH, Tan SS, Choo SP, Chung AYF, Goh BKP. Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence. World J Hepatol 2018; 10:433-447. [PMID: 29988922 PMCID: PMC6033716 DOI: 10.4254/wjh.v10.i6.433] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/10/2018] [Accepted: 03/03/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC). METHODS A systematic review of the published literature was performed using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC. RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%. CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.
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Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore.
| | - Hwee Leong Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Weng Kit Lye
- Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Adrian Kah Heng Chiow
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Siong San Tan
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Su Pin Choo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Alexander Yaw Fui Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
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9
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Galun D, Bogdanovic A, Djokic Kovac J, Bulajic P, Loncar Z, Zuvela M. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative-intent surgery for hepatocellular carcinoma: experience from a developing country. Cancer Manag Res 2018; 10:977-988. [PMID: 29765248 PMCID: PMC5942394 DOI: 10.2147/cmar.s161398] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose The aim of the study was to evaluate a prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) on long-term survival of cirrhotic and noncirrhotic hepatocellular cancer (HCC) patients managed by a curative-intent liver surgery in a developing country. Patients and methods During the study period between November 1, 2001, and December 31, 2012, 109 patients underwent potentially curative hepatectomy for HCC. Data were retrospectively reviewed from the prospectively collected database. The median follow-up was 25 months. NLR was estimated by dividing an absolute neutrophil count by an absolute lymphocyte count from the differential blood count. Receiver operating characteristic curve was constructed to assess the ability of NLR to predict long-term outcomes and to determine an optimal cutoff value for all patients group, the subgroup with cirrhosis, and the subgroup without cirrhosis. The optimal cutoff values were 1.28, 1.28, and 2.09, respectively. Results The overall 3- and 5-year survival rates were 49% and 45%, respectively, for low NLR group and 38% and 26%, respectively, for high NLR group. The difference was statistically significant (p=0.015). Overall survival was similar between low and high NLR groups in patients with cirrhosis; no difference was found between the groups (p=0.124). In patients without cirrhosis, low NLR group had longer overall survival compared with high NLR group (p=0.015). Univariate analysis identified four factors as significant predictors of long-term survival: cirrhosis, Child-Pugh score, platelet count, and NLR. On multivariate analysis, only platelet count and NLR were independent prognostic factors of long-term survival. Conclusion Prognostic value of NLR was confirmed in noncirrhotic HCC patients who underwent curative-intent liver surgery. In HCC patients with cirrhosis, the prognostic role of NLR was not confirmed.
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Affiliation(s)
- Danijel Galun
- HPB Unit, Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical School, University of Belgrade, Belgrade, Serbia
| | | | - Jelena Djokic Kovac
- Medical School, University of Belgrade, Belgrade, Serbia.,Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Belgrade, Serbia
| | - Predrag Bulajic
- HPB Unit, Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade, Serbia
| | - Zlatibor Loncar
- Medical School, University of Belgrade, Belgrade, Serbia.,Emergency Center, Clinical Center of Serbia, Belgrade, Serbia
| | - Marinko Zuvela
- HPB Unit, Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade, Serbia.,Medical School, University of Belgrade, Belgrade, Serbia
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Balogh J, Victor D, Asham EH, Burroughs SG, Boktour M, Saharia A, Li X, Ghobrial RM, Monsour HP. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016; 3:41-53. [PMID: 27785449 PMCID: PMC5063561 DOI: 10.2147/jhc.s61146] [Citation(s) in RCA: 796] [Impact Index Per Article: 88.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.
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Affiliation(s)
- Julius Balogh
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - David Victor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Emad H Asham
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Sherilyn Gordon Burroughs
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Maha Boktour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Ashish Saharia
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Xian Li
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - R Mark Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Howard P Monsour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
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11
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Galun D, Basaric D, Zuvela M, Bulajic P, Bogdanovic A, Bidzic N, Milicevic M. Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols. World J Hepatol 2015; 7:2274-91. [PMID: 26380652 PMCID: PMC4568488 DOI: 10.4254/wjh.v7.i20.2274] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 07/06/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.
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Affiliation(s)
- Danijel Galun
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Dragan Basaric
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Marinko Zuvela
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Predrag Bulajic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Aleksandar Bogdanovic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Nemanja Bidzic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Miroslav Milicevic
- Danijel Galun, Dragan Basaric, Marinko Zuvela, Predrag Bulajic, Aleksandar Bogdanovic, Nemanja Bidzic, Miroslav Milicevic, Clinic of Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
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Schlachterman A, Jr WWC, Hilgenfeldt E, Mitra A, Cabrera R. Current and future treatments for hepatocellular carcinoma. World J Gastroenterol 2015; 21:8478-8491. [PMID: 26229392 PMCID: PMC4515831 DOI: 10.3748/wjg.v21.i28.8478] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 04/27/2015] [Accepted: 06/26/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.
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Yang J, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Is hepatectomy for huge hepatocellular carcinoma (≥ 10 cm in diameter) safe and effective? A single-center experience. Asian Pac J Cancer Prev 2015; 15:7069-77. [PMID: 25227793 DOI: 10.7314/apjcp.2014.15.17.7069] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This retrospective study aimed to validate the safety and effectiveness of hepatectomy for huge hepatocellular carcinoma (HCC). MATERIALS AND METHODS Data of patients who underwent hepatectomy for HCC between January 2006 and December 2012 were reviewed. The patients were divided into three groups: huge HCC(≥ 10 cm in diameter), large HCC(≥ 5 but<10 cm in diameter) and small HCC(<5 cm in diameter). RESULTS Characteristics of pre-operative patients in all three groups were homogeneously distributed except for alpha fetal protein (AFP)(p<0.001).The 30, 60, 90-day post-operative mortality rates were not different among the three groups (p=0.785, p=0.560, and p=0.549). Laboratory data at 1, 3, and 7 days after surgery also did not vary. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates in the huge and large HCC groups were lower than that of the small HCC group (OS: 32.5% vs 36.3% vs 71.2%, p=0.000; DFS: 20.0% vs 24.8% vs 40.7%, p=0.039), but there was no difference between the huge and large HCC groups (OS: 32.5% vs 36.3%, p=0.667; DFS: 20.0% vs 24.8%, p=0.540). In multivariate analysis, five independent poor prognostic factors that affected OS were significantly associated with worse survival (p<0.05), namely, AFP level, macrovascular invasion, Edmondsone Steiner grade, surgical margin and Ishak score. AFP level, macrovascular invasion, microvascular invasion, and surgical margin influenced disease-free survival independently (p<0.05). CONCLUSIONS The safety of hepatectomy for huge HCC is similar to that for large and small HCC; and this approach for huge HCC may achieve similar long-term survival and disease-free survival as for large HCC.
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Affiliation(s)
- Jian Yang
- Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China E-mail :
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Wang X, Bayer ME, Chen X, Fredrickson C, Cornforth AN, Liang G, Cannon J, He J, Fu Q, Liu J, Nistor GI, Cao W, Chen C, Dillman RO. Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma. J Surg Oncol 2015; 111:862-7. [PMID: 25873455 PMCID: PMC6220948 DOI: 10.1002/jso.23897] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 01/29/2015] [Indexed: 12/18/2022]
Abstract
Background and Objectives Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis. Methods Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks. Results HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA. Conclusion Autologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.
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Affiliation(s)
- Xiaojin Wang
- Hospital 85 People's Liberation Army of China, Shanghai, China
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Abstract
Hepatocellular carcinoma (HCC) is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT) representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.
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Affiliation(s)
- Ahmad A. Madkhali
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada
| | - Zahir T. Fadel
- Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada,Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Murad M. Aljiffry
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mazen M. Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Department of Oncology, McGill University, Montreal, Canada,Address for correspondence: Dr. Mazen Hassanain, Assistant Professor of Surgery and Consultant HPB and Transplant Surgery, Department of Surgery, College of Medicine, Scientific Director Liver Disease Research Centre, King Saud University, P.O.Box 25179, Riyadh, 11466, Saudi Arabia. E-mail:
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Zhong JH, Rodríguez AC, Ke Y, Wang YY, Wang L, Li LQ. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore) 2015; 94:e396. [PMID: 25621684 PMCID: PMC4602643 DOI: 10.1097/md.0000000000000396] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/25/2014] [Accepted: 11/26/2014] [Indexed: 01/27/2023] Open
Abstract
This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14, 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.
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Affiliation(s)
- Jian-Hong Zhong
- From the Department of Hepatobiliary Surgery (J-HZ, ACR, Y-YW, L-QL), Affiliated Tumor Hospital of Guangxi Medical University, Nanning; Department of Research (ACR), Creaducate Enterprises Ltd, Kowloon, Hong Kong; and Department of Hepatobiliary Surgery (YK, LW), The Second Affiliated Hospital of Kunming Medical University, Kunming, PR China
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Abstract
BACKGROUND The surgical resection of huge hepatocellular carcinoma (HCC) is still controversial. This study was designed to introduce our experience of liver resection for huge HCC and evaluate the safety and outcomes of hepatectomy for huge HCC. METHODS A total of 258 hepatic resections for the patients with huge HCC were analysed retrospectively from December 2002 to December 2011. The operative outcomes were compared with 293 patients with HCC >5.0 cm but <10.0 cm in diameter. Prognostic factors for long-term survival were evaluated by univariate and multivariate analyses. RESULTS The 1-, 3-, 5-year overall survival rates after liver resection were 84, 62, and 33 %. Overall survival and disease-free survival in huge HCC group and HCC >5.0 cm but <10.0 cm group were similar (P = 0.751, P = 0.493). Solitary huge HCC group has significantly a more longer overall and disease-free survival time than nodular huge HCC (P = 0.026, P = 0.022). Univariate and multivariate analysis revealed that the types of tumour, vascular invasion, and UICC stage were independent prognostic factors for overall survival (P = 0.047, P = 0.037, P = 0.033). CONCLUSIONS Hepatic resection can be performed safely for huge HCC with a low mortality and favorable survival outcomes. Solitary huge HCC has the better surgical outcomes than nodular huge HCC.
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Zhong JH, Xiang BD, Gong WF, Ke Y, Mo QG, Ma L, Liu X, Li LQ. Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization. PLoS One 2013; 8:e68193. [PMID: 23874536 PMCID: PMC3706592 DOI: 10.1371/journal.pone.0068193] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 05/28/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE). METHODS A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model. RESULTS The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE. CONCLUSIONS LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.
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Affiliation(s)
- Jian-Hong Zhong
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Bang-De Xiang
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Wen-Feng Gong
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Yang Ke
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Qin-Guo Mo
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Liang Ma
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Xing Liu
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
- Gastrointestinal Surgery Department, the People’s Hospital of Liuzhou, Liuzhou, People’s Republic of China
| | - Le-Qun Li
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
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Zhong JH, Xiang BD, Gong WF, Ke Y, Mo QG, Ma L, Liu X, Li LQ. Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization. PLoS One 2013. [PMID: 23874536 DOI: 10.137/journal.pone.0068193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS Treatment of patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study compared the long-term survival of patients with BCLC-B HCC who received liver resection (LR) or transarterial chemoembolization (TACE). METHODS A total of 257 and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were retrospectively evaluated. Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were determined by the Cox proportional hazards model. RESULTS The hospital mortality rate was similar between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a significantly higher postoperative complication rate than the TACE group (28 vs. 18.5%; P = 0.04). At the same time, the LR group showed significantly higher overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs. 14%; P<0.001). Moreover, similar results were observed in the propensity score model. Three independent prognostic factors were associated with worse overall survival: serum AFP level (≥400 ng/ml), serum ALT level, and TACE. CONCLUSIONS LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides better long-term overall survival. However, prospective studies are needed to disclose if LR may be regarded as the preferred treatment for these patients as long as liver function is preserved.
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Affiliation(s)
- Jian-Hong Zhong
- Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
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Abstract
The current treatment of HCC is truly multidisciplinary. Notwithstanding, surgical management remains the gold standard which other therapies are compared to. Operative management is divided into transplantation and resection; the latter is further subdivided among open and laparoscopic approaches. Resection has become safer, remains superior to locoregional treatments, and can be a life-prolonging bridge to transplantation. The decision to pursue laparoscopic resection for HCC is driven by safety and a view toward the long-term management of both the malignancy and the underlying liver disease. For patients with a solitary HCC <5 cm in segments 2, 3, 4b, 5, and 6, no evidence of extrahepatic tumor burden, compensated liver disease, and the absence of significant portal hypertension, laparoscopy has an important role. Under these circumstances, resection can be performed with reduced mortality and morbidity and equivalent oncologic outcomes, disease-free survival, and overall survival when compared with similarly selected cirrhotic patients undergoing open resection. Blood loss and transfusion requirements are low, and laparoscopy itself does not expose the patient to complications and does not increase the risk of cancer recurrence or dissemination. Finally, because HCC recurrence remains high in the cirrhotic liver, treatment following surgical resection mandates routine surveillance and treatment by locoregional therapy, reresection, or transplantation as required-the latter two of which are facilitated by an initial laparoscopic resection.
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Galun DA, Bulajic P, Zuvela M, Basaric D, Ille T, Milicevic MN. Is there any benefit from expanding the criteria for the resection of hepatocellular carcinoma in cirrhotic liver? Experience from a developing country. World J Surg 2012; 36:1657-65. [PMID: 22395347 DOI: 10.1007/s00268-012-1544-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with large-size (>10 cm) hepatocellular carcinoma (HCC) in Child B cirrhosis are usually excluded from curative treatment, i.e., hepatic resection, because of marginal liver function and poor outcome. This study was designed to evaluate the feasibility of the radiofrequency (RF)-assisted sequential "coagulate-cut liver resection technique" in expanding the criteria for resection of large HCC in cirrhotic livers with impaired liver function. METHODS Forty patients with Child-Pugh A or B cirrhosis underwent liver resection from December 1, 2001 to December 31, 2008. Of these, 20 patients (13 Child-Pugh A and 7 Child-Pugh B) with advanced stage HCC (stage B and C according to Barcelona-Clinic Liver Cancer Group) underwent major liver resection. The two groups were comparable in terms of patient age, liver cirrhosis etiology, tumor number, and size. RESULTS All resections were performed without the Pringle maneuver. There was no significant difference found between the two groups regarding resection time, perioperative transfusion, postoperative complications, hospital stay, and day 7 values of hemoglobin and liver enzymes. Likewise, there was no significant difference found in the overall survival between Child A and Child B patients who underwent major liver resection CONCLUSIONS RF-assisted sequentional "coagulate-cut liver resection technique" may be a viable alternative for management of patients with advanced HCC in cirrhotic liver with impaired function.
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Affiliation(s)
- Danijel A Galun
- First Surgical Clinic, Clinical Center of Serbia, Koste Todorovica 6, 11 000, Belgrade, Serbia.
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Shrager B, Jibara GA, Tabrizian P, Schwartz ME, Labow DM, Hiotis S. Resection of large hepatocellular carcinoma (≥10 cm): A unique western perspective. J Surg Oncol 2012; 107:111-7. [DOI: 10.1002/jso.23246] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 07/25/2012] [Indexed: 12/16/2022]
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Muros-Ortega M, Díaz-Carrasco M, Vila-Clérigues N, Mendoza-Otero F, de la Rubia A, Capel Alemán A. Experiencia de uso de partículas DC Bead® cargadas con doxorrubicina en quimioembolización hepática. FARMACIA HOSPITALARIA 2011; 35:172-9. [DOI: 10.1016/j.farma.2010.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2010] [Revised: 06/08/2010] [Accepted: 06/20/2010] [Indexed: 02/08/2023] Open
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Kupcsulik P. [Surgical oncology of hepatocellular carcinoma (HCC)]. Orv Hetil 2010; 151:1483-7. [PMID: 20807694 DOI: 10.1556/oh.2010.28905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Incidence of hepatocellular carcinoma (HCC) increases worldwide. 600 new cases may occur in Hungary yearly, but statistical data show much fewer patients seen in hepatological care units. Despite of new drug sorafenib or ablative techniques, surgical methods remain the most effective treatment of HCC. Results of orthotropic liver transplantation (OTLX) in selected HCC cases have been becoming promising lately. Hungarian transplant capacity and HCC stadium levels in the majority of diagnosed cases exclude OTLX for all patients. Surgical resection is determined by the functional liver remnant (FLR). Cirrhotic patients tolerate left lateral segmentectomy. Tumors of the right lobe after occlusion of right main portal branch - if left lobe regeneration is satisfying - might be resected even in cirrhotic liver. Intra-operative preconditioning significantly diminishes serum levels of ischemia-reperfusion markers and operative risk. At the First Department of Surgery of Semmelweis University, 2167 liver tumors were operated between 1996 and 2009, including 254 HCC cases. Radical resection was performed in 211 (82.7% resection rate). Laparoscopic liver resection is becoming popular all over the world, representing less surgical injury compared to open procedure. Indication of minimal invasive liver resection is therefore specifically important in cirrhotic patients.
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Affiliation(s)
- Péter Kupcsulik
- Semmelweis Egyetem, Altalános Orvostudományi Kar I. Sebészeti Klinika, Budapest.
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Ba MC, Cui SZ, Lin SQ, Tang YQ, Wu YB, Zhang XL. Resection of a giant hepatocellular carcinoma weighing over ten kilograms. World J Gastroenterol 2010; 16:1422-4. [PMID: 20238412 PMCID: PMC2842537 DOI: 10.3748/wjg.v16.i11.1422] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The authors report a giant hepatocellular carcinoma (HCC) with a diameter over 30 cm and weight over 10 kg that was resected completely. A 62-year-old man was admitted because of continuous abdominal uplift. A computed tomography scan demonstrated that the entire abdomen was filled with a giant tumor containing both cystic and solid components with a size of 29 cm × 22 cm. The huge tumor was successfully resected without any complication, such as massive hemorrhage or visceral injuries. The size and weight of the tumor were 35 cm × 30 cm × 15 cm and 10 050 g, respectively. Pathological examination showed that the tumor was a well-differentiated HCC, and α-fetoprotein was positive. Postoperative syndrome, characterized by hypovolemic shock, diarrhea and urine retention, was observed and induced by abdominal decompression. This syndrome was resolved with expectant treatment. The patient was still alive without recurrence after a 27-mo follow-up.
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Ruzzenente A, Capra F, Pachera S, Iacono C, Piccirillo G, Lunardi M, Pistoso S, Valdegamberi A, D'Onofrio M, Guglielmi A. Is liver resection justified in advanced hepatocellular carcinoma? Results of an observational study in 464 patients. J Gastrointest Surg 2009; 13:1313-1320. [PMID: 19418103 DOI: 10.1007/s11605-009-0903-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2009] [Accepted: 04/15/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE The role of liver resection in advanced hepatocellular carcinoma (multinodular or with macroscopic vascular involvement) is still controversial. The aim of this study is to evaluate the role of surgical resection compared to other therapeutic modalities in patients with advanced hepatocellular carcinoma (HCC). METHODS Four hundred sixty four patients with HCC observed from 1991 to 2007 were included in the study. All the patients were evaluated for the treatment of HCC in relation to the severity of liver impairment and tumor stage. All the patients included in the study had no evidence of distant metastases. RESULTS Median follow up time for surviving patients was 25 months (range 1-155). Two-hundred and eighty-three patients were in Child-Pugh class A, 161 in class B, and 20 in class C. Two-hundred and seventy-one patients had single HCC, 121 patients had two or three HCCs, and 72 more than three HCCs. One-hundred and thirty-six patients (29.3%) were submitted to liver resection (LR), 232 (50.0%) to local ablative therapies (LAT) (ethanol injection, radiofrequency ablation, chemoembolization), eight (1.7%) to liver transplantation (LT), and 88 (19%) to supportive therapy (ST). Median survival time for all patients was 36 months (95% CI 24-36). Median survival time was 57 months for LR, 30 months for LAT, and 8 months for ST, with a 5-year survival of 47%, 20%, and 2.5%, respectively (p = 0.001). Actuarial 5-year survival for patients submitted to LT was 75%. Overall survival was significantly shorter in patients with multiple HCCs compared to single HCC, with median survival times of 39, 16, and 11 months for patients with a single HCC, with two to three HCCs, and with more than three HCCs, respectively (p = 0.01). Survival for patients with single HCC was significantly longer in patients submitted to LR compared to LAT and ST with median survival times of 57, 37, and 14 months, respectively (p = 0.02). Also, in patients with multinodular HCCs (2-3 HCCs) LR showed the best results with a median survival time of 58 months compared to 22 and 8 months for LAT and ST (p = 0.01). In patients with more than three HCCs, LR did not show different results compared to LAT and ST. Seventy-three patients had evidence of macroscopic vascular involvement; median survival in this subgroup of patients was significantly shorter compared to patients without vascular involvement, 10 and 36 months, respectively. Survival for patients with macroscopic vascular involvement submitted to LR or LAT was significant longer compared to ST, with mean survivals of 27, 30, and 12 months, respectively (p = 0.01). CONCLUSIONS The present study shows that the surgery can achieve good results in patients with single HCC and good liver function. Also, patients with multinodular HCCs (two to three nodules) could benefit from LR where survival is longer than after LAT or ST. In patients with more than three HCCs, LR have similar results of LAT. Macroscopic vascular invasion is a major prognostic factor, and the LR is justified in selected patients, where it can allow good long-term results compared to ST.
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Affiliation(s)
- Andrea Ruzzenente
- Department of Surgery and Gastroenterology, Division of General Surgery A, GB Rossi University Hospital, University of Verona Medical School, Piazzale LA Scuro 10, 37134, Verona, Italy.
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Benson AB, Abrams TA, Ben-Josef E, Bloomston PM, Botha JF, Clary BM, Covey A, Curley SA, D'Angelica MI, Davila R, Ensminger WD, Gibbs JF, Laheru D, Malafa MP, Marrero J, Meranze SG, Mulvihill SJ, Park JO, Posey JA, Sachdev J, Salem R, Sigurdson ER, Sofocleous C, Vauthey JN, Venook AP, Goff LW, Yen Y, Zhu AX. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 2009; 7:350-91. [PMID: 19406039 PMCID: PMC4461147 DOI: 10.6004/jnccn.2009.0027] [Citation(s) in RCA: 411] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University, USA
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