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Qiu S, Chen R, Hu J, Han T. The prognosis of fibrolamellar carcinoma versus conventional hepatocellular carcinoma: a study based on propensity score matching. Scand J Gastroenterol 2023; 58:1351-1358. [PMID: 37353942 DOI: 10.1080/00365521.2023.2227305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 06/12/2023] [Accepted: 06/14/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND The prognosis of fibrolamellar carcinoma (FLC) versus conventional hepatocellular carcinoma (HCC) remains controversial. Thus, this study aimed to compare the prognosis of FLC and HCC. METHODS Patients with FLC and HCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2015 were included. Propensity score matching (PSM) was performed to balance the clinical characteristics between FLC and HCC. Cox regression and Kaplan-Meier analysis were applied to identify the effect of pathology in prognosis before and after match in the whole cohort, as well as in subgroups of fibrosis score, AJCC stage and therapy. RESULTS A total of 213 patients with FLC and 33365 patients with HCC between 2000 and 2015 were identified. Before matching, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in FLC than HCC. After matching, FLC patients had better OS than HCC patients, but the CSS was similar between groups. Further analyses found that in patients at early stage (AJCC I-III) and/or accepted curative therapy, the prognosis was comparable between HCC and FLC. In patients without cirrhosis (F0), the HCC patients had similar prognosis with FLC patients. Prognosis benefit of FLC was observed in subgroups of AJCC stage IV and non-curative therapy, however, the concomitant diseases may affect the results. CONCLUSIONS The prognosis of FLC was significantly better than HCC before matching. However, after matching for clinical characteristics, the CSS was comparable between FLC and HCC.
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Affiliation(s)
- Shaotian Qiu
- The School of Medicine, Nankai University, Tianjin, P.R. China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, P.R. China
| | - Rui Chen
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center of Tianjin Medical University, Tianjin, P.R. China
| | - Jiaxuan Hu
- The School of Medicine, Nankai University, Tianjin, P.R. China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, P.R. China
| | - Tao Han
- The School of Medicine, Nankai University, Tianjin, P.R. China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, P.R. China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center of Tianjin Medical University, Tianjin, P.R. China
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Abdelhamed W, El-Kassas M. Fibrolamellar hepatocellular carcinoma: A rare but unpleasant event. World J Gastrointest Oncol 2022; 14:1103-1114. [PMID: 35949219 PMCID: PMC9244987 DOI: 10.4251/wjgo.v14.i6.1103] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/19/2022] [Accepted: 05/08/2022] [Indexed: 02/06/2023] Open
Abstract
Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC), comprising 1%-9% of all HCCs. FLC is a poorly understood malignancy, which seems to be more prevalent in young patients with no underlying liver diseases. The term "fibrolamellar" is derived from thick fibrous collagen bands surrounding the tumor cells. Unlike HCC, cirrhosis and viral hepatitis infection are not predisposing to FLC, and it is not associated with elevations in serum alpha-fetoprotein. FLC patients often present with vague abdominal pain, nausea, malaise, and weight loss. Most cases present are at an advanced stage at the time of initial diagnosis. However, curative treatment options can still be offered to up to 70% of patients. Surgery (resection/liver transplantation) is the mainstay of treatment and the only potentially curative option. FLCs have been less chemo-responsive than the conventional HCC, however, in advanced cases, multimodality treatments can be effective. Recent advances in molecular studies of FLC have found a unique DNAJB1-PRKACA fusion transcript in most of the cases studied. The review aims to describe clinical characteristics, diagnostic methods, and therapeutic modalities for this rare tumor to raise awareness among clinicians and surgeons.
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Affiliation(s)
- Walaa Abdelhamed
- Department of Endemic Medicine, Sohag University, Sohag 14322, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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3
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Zakka K, Jiang R, Alese OB, Shaib WL, Wu C, Wedd JP, Sellers MT, Behera M, El-Rayes BF, Akce M. Clinical outcomes of rare hepatocellular carcinoma variants compared to pure hepatocellular carcinoma. J Hepatocell Carcinoma 2019; 6:119-129. [PMID: 31413960 PMCID: PMC6660638 DOI: 10.2147/jhc.s215235] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 06/26/2019] [Indexed: 12/12/2022] Open
Abstract
Background HCC variants are rare primary hepatic tumors. The aim of this study is to compare clinical characteristics and outcomes of HCC variants with pure HCC. Methods Patients diagnosed between 2004 and 2013 with ICD-O-3 8180/3 and 8170/3-8175/3 were identified from the National Cancer Database. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS). Results 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p<0.001). Pure HCC (10.6%) underwent surgical resection without transplant less often than variants except for scirrhous (9.9%) (p<0.001). More than a third of patients in each histological type received chemotherapy. FLHCC had the best 5-year OS (38.7%), spindle cell and pleomorphic had the worst (9.6% and 13.0%). In multivariate analysis stratified by histology variants, chemotherapy was associated with improved OS in all histologies except for scirrhous and pleomorphic HCC. Conclusion HCC variants underwent surgical resection more often than pure HCC. FLHCC had the best 5-year OS. Liver transplant was commonly performed in HCC variants.
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Affiliation(s)
- Katerina Zakka
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Renjian Jiang
- Department of Research Informatics, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Olatunji B Alese
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Walid L Shaib
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Christina Wu
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Joel P Wedd
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Marty T Sellers
- Division of General and GI Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Madhusmita Behera
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.,Department of Research Informatics, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Mehmet Akce
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
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Wahab MA, El Hanafy E, El Nakeeb A, Ali MA. Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma (experience with 22 patients over a 15-year period). World J Gastrointest Surg 2017; 9:61-67. [PMID: 28289511 PMCID: PMC5329705 DOI: 10.4240/wjgs.v9.i2.61] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 11/19/2016] [Accepted: 12/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinicopathological features and the surgical outcomes of patients with fibrolamellar hepatocellular carcinoma (FL-HCC) over a 15-year period.
METHODS This is a retrospective study including 22 patients with a pathologic diagnosis of FL-HCC who underwent hepatectomy over a 15-year period. Tumor characteristics, survival and recurrence were evaluated.
RESULTS There were 11 male and 11 female with a median age of 29 years (range from 21 to 58 years). Two (9%) patients had hepatitis C viral infection and only 2 (9%) patients had alpha-fetoprotein level > 200 ng/mL. The median size of the tumors was 12 cm (range from 5-20 cm). Vascular invasion was detected in 5 (23%) patients. Four (18%) patients had lymph node metastases. The median follow up period was 42 mo and the 5-year survival was 65%. Five (23%) patients had a recurrent disease, 4 of them had a second surgery with 36 mo median time interval. Vascular invasion is the only significant negative prognostic factor
CONCLUSION FL-HCC has a favorable prognosis than common HCC and should be suspected in young patients with non cirrhotic liver. Aggressive surgical resection should be done for all patients. Repeated hepatectomy should be considered for these patients as it has a relatively indolent course.
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Kassahun WT. Contemporary management of fibrolamellar hepatocellular carcinoma: diagnosis, treatment, outcome, prognostic factors, and recent developments. World J Surg Oncol 2016; 14:151. [PMID: 27215576 PMCID: PMC4877801 DOI: 10.1186/s12957-016-0903-8] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Accepted: 05/10/2016] [Indexed: 02/08/2023] Open
Abstract
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially curative treatment option for patients who have resectable disease is surgery either liver resection (LR) or liver transplantation (LT). When performed in a context of aggressive therapy, long-term outcomes after surgery, particularly liver resection for FL-HCC, were favorable. The clinical outcome of patients with unresectable disease is suboptimal with median survival of less than 12 months. The aim of this review is to update the available evidence on diagnosis, treatment options, outcome predictors, and recent developments of patients with this rare disease and to provide a summarized overview of the available literature.
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Affiliation(s)
- Woubet Tefera Kassahun
- Department of Surgery II, Faculty of Medicine, Clinic for Visceral, Transplantation, Thoracic and Vascular Surgery, OKL, University of Leipzig, Liebig Strasse 20, 04103, Leipzig, Germany.
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Eggert T, McGlynn KA, Duffy A, Manns MP, Greten TF, Altekruse SF. Fibrolamellar hepatocellular carcinoma in the USA, 2000-2010: A detailed report on frequency, treatment and outcome based on the Surveillance, Epidemiology, and End Results database. United European Gastroenterol J 2014; 1:351-7. [PMID: 24917983 DOI: 10.1177/2050640613501507] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 07/17/2013] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Epidemiological and clinical information on fibrolamellar hepatocellular carcinoma (fHCC) is scarce. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis with the aim of collecting information to better understand the biology and clinical aspects of this rare disease. DESIGN Incidence trends, race- and age-specific rates, tumor size, first course surgery and five-year relative survival of 191 US cases (SEER) diagnosed with fHCC during 2000-2010 were compared to cases with hepatocellular carcinoma (HCC), HCC-not otherwise specified (HCC-NOS) and other HCC-types. RESULTS While HCC-NOS incidence rates increased by 5.2% annually from 2000-2008 (p < 0.05) before leveling, the 1.3% change in fHCC incidence was not statistically significant. The rates of fHCC were similar across ethnic groups while HCC-NOS incidence rates were higher among non-whites. Although 16% of fHCC patients had primary tumors ≤5 cm compared to 37% of HCC-NOS cases five-year survival was better among fHCC (34%) than HCC-NOS cases (16%). Fibrolamellar HCC cases of 0-39 years of age were more likely to receive radiofrequency ablation, transplant or resection than HCC-NOS cases of that age. Survival was similar among fibrolamellar and HCC-NOS cases receiving surgery. CONCLUSION In this largest case series, fibrolamellar and HCC-NOS age- and race-specific incidence rates and time trends differed. Despite larger tumor size than HCC-NOS cases fibrolamellar cases received surgery more often and had better survival rates. Differences in co-morbidity may influence treatment. Studies of fHCC biology, including by age, are recommended.
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Affiliation(s)
- Tobias Eggert
- Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute, Bethesda, USA ; Department of Gastroenterology, Hepatology and Endocrinology, School of Medicine, Hannover, Germany
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA
| | - Austin Duffy
- Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute, Bethesda, USA
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, School of Medicine, Hannover, Germany
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute, Bethesda, USA
| | - Sean F Altekruse
- Division of Cancer Control & Population Sciences, National Cancer Institute Rockville, USA
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Cheng J, Huang T, Li Y, Guo Y, Zhu Y, Wang Q, Tan X, Chen W, Zhang Y, Cheng W, Yamamoto T, Jing X, Huang J. AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma. PLoS One 2014; 9:e93256. [PMID: 24709998 PMCID: PMC3977828 DOI: 10.1371/journal.pone.0093256] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Accepted: 03/04/2014] [Indexed: 02/05/2023] Open
Abstract
AMP-activated protein kinase (AMPK) is a central metabolic sensor and plays an important role in regulating glucose, lipid and cholesterol metabolism. Therefore, AMPK is a key therapeutic target in diabetes. Recent pilot studies have suggested that diabetes drugs may reduce the risk of cancer by affecting the AMPK pathway. However, the association between AMPK and the proliferation of hepatocellular carcinoma (HCC) is unknown. In this study, we investigated the relationship between AMPK activity and the proliferation of HCC in cell lines, nude mice and human clinic samples. We first investigated the relationship between AMPK activity and cell proliferation in two HCC cell lines, PLC/PRF/5 and HepG2, by two AMPK activators, 5-aminoimidazole-4-carboxamide-1-h-D-ribofuranoside (AICAR) and metformain. AICAR and metformin treatment significantly inhibited the proliferation of HCC cells and induced cell cycle arrest at G1-S checkpoint. We then observed that metformin abrogated the growth of HCC xenografts in nude mice. The clinical pathology of AMPK activity in HCC, including cell proliferation, differential grade, tumor size and microvessel density, was studied by using 30 clinical tissue samples. In HCC tissue samples, phosphorylated AMPK was expressed mainly in cytoplasm. AMPK activity decreased significantly in HCC in comparison with paracancerous liver tissues (P<0.05). AMPK activity was negatively correlated with the level of Ki-67 (a marker of cell proliferation), differential degradation and tumor size (P<0.05), but not with microvessel density, hemorrhage or necrosis in HCC. Our findings suggest that AMPK activity inhibits the proliferation of HCC and AMPK might be an effective target for prevention and treatment of HCC.
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Affiliation(s)
- Jidong Cheng
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- * E-mail: (JC); (XJ); (JH)
| | - Tianliang Huang
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Youfeng Li
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yubai Guo
- Department of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yuzhang Zhu
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Qingjia Wang
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Xiaojun Tan
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Weisheng Chen
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yongneng Zhang
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Weijie Cheng
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Tetsuya Yamamoto
- Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Xubin Jing
- Department of Internal Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- * E-mail: (JC); (XJ); (JH)
| | - Jiexiong Huang
- Department of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- * E-mail: (JC); (XJ); (JH)
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Mavros MN, Mayo SC, Hyder O, Pawlik TM. A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg 2012; 215:820-30. [PMID: 22981432 DOI: 10.1016/j.jamcollsurg.2012.08.001] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2012] [Revised: 08/01/2012] [Accepted: 08/01/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver tumor presenting earlier in life than nonfibrolamellar hepatocellular carcinoma (NFL-HCC), with distinct epidemiologic and clinical characteristics. Although FLC is believed to have a better prognosis than NFL-HCC, data on treatment and prognosis are scarce. We performed a systematic review to investigate treatment options and clinical outcomes of patients with FLC. STUDY DESIGN The study is a systematic review of the literature and pooled analysis of individual patient data. RESULTS A total of 35 series were analyzed, reporting on 575 patients (52% female, elevated alpha-fetoprotein in 10%, cirrhosis in 3%, hepatitis B in 2%), most of whom were treated with partial hepatectomy (55%) or orthotopic liver transplantation (23%). Nineteen studies provided data on 206 individual patients with a median age of 21 years and tumor size of 12 cm. Median overall survival (OS) was 39 months; 1-year, 3-year, and 5-year OS rates were 85%, 53%, and 44%, respectively. For patients treated with liver resection, median OS was 18.5 years and 1-year, 3-year, and 5-year OS were 93%, 80%, and 70%, respectively. Based on data from 15 studies, FLC appeared to follow a relatively indolent course compared with NFL-HCC. CONCLUSIONS Patients with FLC treated with partial hepatectomy have excellent long-term survival, with 5-year overall survival reaching 70%. Patients fared worse with the use of other therapeutic options including chemotherapy, intra-arterial therapy, and transplantation, although data directly comparing resection vs transplantation were limited.
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Affiliation(s)
- Michael N Mavros
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287, USA
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9
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Mroz RM, Korniluk M, Swidzinska E, Dzieciol J, Czaban J, Panek B, Chyczewska E. Lung mass in a 28-year-old male: a case report of a rare tumor. Eur J Med Res 2011; 15 Suppl 2:95-7. [PMID: 21147631 PMCID: PMC4360372 DOI: 10.1186/2047-783x-15-s2-95] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
A twenty eight-year-old male presented with a two week history of dyspnea, cough, hemoptysis, chest pain, and fever 38-39°C. He also complained of loss of appetite, general weakness and left leg pain for two months preceding admission. He was referred with suspicion of lung tumor to our institution. Chest X-ray showed almost total atelectasis of the right lung with compensatory overinflation of the contralateral lung. Using computed tomography (CT), a lesion of diameter of 19.3 x 14.1 x 19.1 cm in the right lung, pleuritis, Th3 osteolysis, and compensatory overinflation of the left lung was seen. Bronchoscopy revealed a total obstruction of the right main bronchus due to submucosal infiltration and compression of the right main bronchus with negative histology of bronchial biopsy specimens. Transthoracic fine needle aspiration revealed celullae suspectae probabiliter neoplasmaticae suggesting tumor fusocellularis. USG of the abdomen revealed liver with numerous heterogeneous, solid areas hypo- and hyperechogenic, some of them with features of liquid or the disintegration up to diameter of 74 mm. Subsequent fine needle aspirations of the thorax and liver revealed fibrolamellar hepatocarcinoma and carcinoma adenoides of the lung. Patient underwent chemotherapy with 5-FU/DDP/VCR with no response. This report presents a case of a rare lung metastasis from FL-HCC.
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Affiliation(s)
- Robert M Mroz
- Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland.
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El-Gazzaz G, Wong W, El-Hadary M, Gunson B, Mirza D, Mayer A, Buckets J, McMaster P. Outcome of liver resection and transplantation for fibrolamellar hepatocellular carcinoma. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb02071.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Tsilividis B, Huet E, Lubrano J, Lacaze L, Lestrat JP, François A, Riachi G, Scotté M. Late supra-diaphragmatic lymph node recurrence following resection of a fibrolamellar hepatocarcinoma: an unusual case. Surg Radiol Anat 2009; 32:123-7. [DOI: 10.1007/s00276-009-0564-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2009] [Accepted: 09/14/2009] [Indexed: 12/31/2022]
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Kakar S, Chen X, Ho C, Burgart LJ, Sahai V, Dachrut S, Yabes A, Jain D, Ferrell LD. Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization. Mod Pathol 2009; 22:134-41. [PMID: 18997738 DOI: 10.1038/modpathol.2008.178] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Fibrolamellar hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma with distinct clinical and histological features, and better survival compared with conventional hepatocellular carcinoma in some but not all series. We performed a comparative genomic hybridization analysis on 11 fibrolamellar carcinomas and correlated the findings with clinicopathologic features and survival. Chromosomal imbalances were identified in six cases (55%), whereas the other five (45%) yielded normal results. The mean number of aberrations per case was 3.9 for all cases and 7.2 in abnormal cases. Among the six abnormal cases, gains or losses were observed at 3 loci in two cases, 7 loci in one case, 8 loci in two cases and 14 loci in one case. The most common abnormalities were observed in chromosomes 7, 8 and 18, with 7q gain in five cases and 7p gain in four cases. Aberrations associated with intermediate or advanced conventional hepatocellular carcinomas, including losses at 3q, 4q and 13q were identified in 17-33% of fibrolamellar carcinomas. There was no correlation of chromosomal changes with age, gender and tumor size. The 5-year survival among the six patients with no chromosomal abnormalities was 80% (4/5) compared with 33% (2/6) in patients with chromosomal abnormalities (P=0.1). In conclusion, fibrolamellar carcinomas show fewer chromosomal abnormalities compared with those reported in literature for conventional hepatocellular carcinoma. The most common abnormalities occur in chromosomes 7 and 8. Fibrolamellar carcinomas with chromosomal changes appear to behave more aggressively compared with cases with no cytogenetic abnormalities. The favorable outcome in some fibrolamellar carcinomas may be due to absent or low number of cytogenetic aberrations.
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Affiliation(s)
- Sanjay Kakar
- Department of Pathology, University of California, San Francisco, CA, USA.
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13
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Lin CL, Chen JD, Liu CJ, Lee PH, Chen PJ, Lai MY, Kao JH, Chen DS. Clinicopathological differences between hepatitis B viral genotype B- and C-related resectable hepatocellular carcinoma. J Viral Hepat 2007; 14:64-9. [PMID: 17212646 DOI: 10.1111/j.1365-2893.2006.00776.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Clinical and pathogenic differences exist between hepatitis B viral (HBV) genotypes B and C, and genotype C has a higher risk of hepatocellular carcinoma (HCC) development than genotype B. The aim of this study was to investigate whether HBV genotypes B and C influence the clinicopathological features of patients with resectable HCC. Stored serum samples from 193 patients with resectable HBV-related HCC were tested for HBV genotypes by a molecular method. Of 193 patients undergoing resection of HCC, 107 (55%) and 86 (45%) were infected with genotypes B and C, respectively. Compared with genotype C patients, genotype B patients were less likely to be associated with liver cirrhosis (33%vs 51%, P = 0.01). Pathologically, genotype B patients had a higher rate of solitary tumour (94%vs 86%, P = 0.048) and more satellite nodules (22%vs 12%, P = 0.05) than genotype C patients. Our results indicate that genotype B-related HCC is less associated with liver cirrhosis and has a higher frequency of solitary tumour as well as more satellite nodules than genotype C-related HCC. These characteristics may contribute to the recurrence patterns and prognosis of HBV-related HCC in patients with genotype B or C infection.
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Affiliation(s)
- C-L Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan
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14
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Kakar S, Burgart LJ, Batts KP, Garcia J, Jain D, Ferrell LD. Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis. Mod Pathol 2005; 18:1417-23. [PMID: 15920538 DOI: 10.1038/modpathol.3800449] [Citation(s) in RCA: 116] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Fibrolamellar carcinoma arises in noncirrhotic livers of young individuals and has been considered to be less aggressive than conventional hepatocellular carcinoma. This study compares survival and clinicopathologic features of fibrolamellar carcinoma with hepatocellular carcinoma arising in noncirrhotic and cirrhotic livers. Clinical and pathologic features including age, gender, tumor size, stage and survival were recorded in 20 resected cases of fibrolamellar carcinoma. Survival was compared with resected hepatocellular carcinoma without (n=32) and with cirrhosis (n=30). Proliferative activity was determined by immunohistochemistry for Ki-67. In all, 12 (60%) patients with fibrolamellar carcinoma died during follow-up; the 5-year survival was 45%. Mortality in fibrolamellar carcinoma was higher with metastatic disease at presentation (6/7, 86% vs 5/13, 39%, P=0.06). Age, gender and tumor size did not correlate with survival. The 5-year (45 vs 56%, P=0.4) as well as overall survival (40 vs 56.3%, P=0.3) was similar in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis. The 5-year and overall survival in hepatocellular carcinoma with cirrhosis was 27 and 23.3%, respectively, which was not significantly different compared to fibrolamellar carcinoma (P=0.2). Among the cases without metastases at presentation, 5-year survival in fibrolamellar carcinoma (62%) and hepatocellular carcinoma without cirrhosis (57%) was significantly better (P=0.03) than hepatocellular carcinoma with cirrhosis (27%). The mean Ki-67 index was similar in all three groups (P=0.1). In conclusion, fibrolamellar carcinoma is an aggressive neoplasm with 45% 5-year survival and overall mortality of 60%. Nearly half the patients develop lymph node or distant metastasis. The prognosis of fibrolamellar carcinoma is similar to conventional hepatocellular carcinoma. Among nonmetastatic cases, the prognosis is better in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis compared to hepatocellular carcinoma with cirrhosis. The better outcome in fibrolamellar carcinoma appears to be due to the absence of cirrhosis rather than its distinct clinicopathologic features.
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Affiliation(s)
- Sanjay Kakar
- Department of Anatomic Pathology, UCSF/VA Medical Center, San Francisco, CA 94121, USA.
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15
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Wang CS, Lin CL, Lee HC, Chen KY, Chiang MF, Chen HS, Lin TJ, Liao LY. Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma. World J Gastroenterol 2005; 11:6115-9. [PMID: 16273636 PMCID: PMC4436626 DOI: 10.3748/wjg.v11.i39.6115] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2005] [Revised: 04/06/2005] [Accepted: 04/09/2005] [Indexed: 02/06/2023] Open
Abstract
AIM Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.
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Affiliation(s)
- Chaur-Shine Wang
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, No. 10, Sec. 4, Ren-ai Road, Da-an District Taipei City 106, Taiwan, China
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16
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Moreira M, Nicoluzzi JEL, Caron PE. Manejo terapêutico do hepatocarcinoma fibrolamelar. Rev Col Bras Cir 2005. [DOI: 10.1590/s0100-69912005000200012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Abstract
Hepatocellular carcinoma is one of the most common causes of cancer death worldwide. Numerous surgical and nonsurgical treatment options are available for the management of patients with HCC. Successful long-term outcome is dependent on early detection of HCC, as well as accurate delineation of the number and location of tumor nodules. We present the different manifestations of hepatocellular carcinoma as depicted by multidetector-row CT with advanced image processing.
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Affiliation(s)
- Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
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18
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Marsh JW, Geller DA, Finkelstein SD, Donaldson JB, Dvorchik I. Role of liver transplantation for hepatobiliary malignant disorders. Lancet Oncol 2004; 5:480-8. [PMID: 15288237 DOI: 10.1016/s1470-2045(04)01527-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The role of liver transplantation for hepatobiliary malignant disorders remains controversial and will remain so until several crucial issues are resolved, the main difficulty being the shortage of organ donors. Furthermore, a consensus needs to be reached within the transplantation community on the tumour stage at which each disorder is too advanced to be salvaged by liver transplantation. Despite these limitations, there are generally accepted criteria that define when transplantation can, and should, be offered for hepatobiliary malignant disorders.
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Affiliation(s)
- J Wallis Marsh
- Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
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19
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide. Numerous surgical and nonsurgical treatment options are available for treating patients with HCC. Successful long-term outcome is dependent on early detection and accurate delineation of the number and location of tumor nodules. Noninvasive imaging modalities, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography, are commonly used in the initial evaluation of these patients. Herein, the authors present the different manifestations of HCC with these imaging modalities and the role of imaging in the follow-up of patients after nonsurgical treatment.
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Affiliation(s)
- Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, 600 N. Wolfe Street, Room 100, Baltimore, MD 21287, USA.
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20
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Molmenti EP, Klintmalm GB. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry. Liver Transpl 2002; 8:736-48. [PMID: 12200772 DOI: 10.1053/jlts.2002.34879] [Citation(s) in RCA: 103] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor.
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Affiliation(s)
- Ernesto P Molmenti
- Baylor University Medical Center, Transplantation Services, Dallas, TX 75246, USA
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21
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Arista-Nasr J, Gutierrez-Villalobos L, Nuncio J, Maldonaldo H, Bornstein-Quevedo L. Fibrolamellar hepatocellular carcinoma in mexican patients. Pathol Oncol Res 2002; 8:133-7. [PMID: 12172578 DOI: 10.1007/bf03033723] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
UNLABELLED The aim of this report is to describe the frequency, clinical, and morphologic characteristics of fibrolamellar hepatocellular carcinoma in Mexican patients. Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma. Although this tumor appears to be predominant among the Caucasian population of the U.S, FLHCC has been described in many other countries. The frequency and characteristics of FLHCC in Latin American population is almost unknown. The clinico-pathologic characteristics of seven (5.8%) Mexican patients with FLHCC, obtained among 121 hepato-cellular carcinomas are described. The frequency of these tumors was compared with the frequency reported in other geographic areas in the international literature between 1980 and 1999. There were four women and three men. Two patients had taken oral contraceptives for six months and a year prior to diagnosis; another patient had positive serology for the hepatitis B virus. Common symptoms included a palpable mass, abdominal pain and weight loss; two patients presented jaundice. In two patients the tumor had been removed eight and three years previously, and they were readmitted when FLHCC recurred. In three patients the diagnosis was suspected in radiological studies (computed tomography and/or magnetic resonance). Laboratory tests were non-specific. In four patients, resection of the tumor was performed, and in the remaining three the neoplasm was diagnosed by percutaneous hepatic biopsy. Two patients had died of disease at the time of the study, and another was alive with recurrent disease. CONCLUSIONS fibrolamellar hepatocarcinoma is an uncommon, but not an exceptional neoplasm in our population and represents 5.8% of all hepatocarcinomas reviewed.
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Affiliation(s)
- Julian Arista-Nasr
- Department of Pathology, Instituto National de Cíencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14000, Mexiko.
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22
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Hemming A, Gallinger S. Liver. Surgery 2001. [DOI: 10.1007/978-3-642-57282-1_30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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23
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24
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Ichikawa T, Federle MP, Grazioli L, Marsh W. Fibrolamellar hepatocellular carcinoma: pre- and posttherapy evaluation with CT and MR imaging. Radiology 2000; 217:145-51. [PMID: 11012437 DOI: 10.1148/radiology.217.1.r00se46145] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
PURPOSE To determine the features of advanced hepatic and extrahepatic fibrolamellar hepatocellular carcinomas (HCCs) and their effects on immediate surgical management and tumor recurrence. MATERIALS AND METHODS Thirty-one patients with fibrolamellar HCC underwent pretherapy computed tomography (CT); 11 underwent pretherapy magnetic resonance (MR) imaging. All 40 patients underwent posttherapy CT; four, follow-up MR imaging. Imaging, surgical, and histopathologic findings were correlated. RESULTS Twenty-five (81%) patients had solitary tumors (mean maximum diameter, 13 cm). Thirteen (42%) patients had intrahepatic biliary obstruction; 27 (87%) patients had involvement of the portal or hepatic veins. Thirteen (42%) had extrahepatic tumor spread, nine (29%) had distant metastases on pretherapy images, and 20 (65%) had lymphadenopathy. Thirty-two (80%) of 40 patients underwent exploration surgery; curative resection was attempted in 25 (62%), including four patients who underwent liver transplantation. Only 17 patients were considered to have had hepatic and extrahepatic tumors completely excised. Tumor recurred in all eight of the 17 patients who had extrahepatic disease at pretherapy CT and in four of the seven patients who seemed to have tumor limited to the liver. A combination of repeat tumor resection and adjuvant chemotherapy resulted in prolonged tumor-free survival in some cases. CONCLUSION Fibrolamellar HCC frequently demonstrates aggressive local invasion and nodal and distant metastases. Pretherapy and follow-up imaging are important for staging, surveillance, and optimal management. Aggressive surgical resection may be helpful to control fibrolamellar HCC and to prolong survival in appropriately selected cases.
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Affiliation(s)
- T Ichikawa
- Department of Radiology, and Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213-2582, USA
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25
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Ichikawa T, Federle MP, Grazioli L, Madariaga J, Nalesnik M, Marsh W. Fibrolamellar hepatocellular carcinoma: imaging and pathologic findings in 31 recent cases. Radiology 1999; 213:352-61. [PMID: 10551212 DOI: 10.1148/radiology.213.2.r99nv31352] [Citation(s) in RCA: 142] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To review characteristic findings of fibrolamellar hepatocellular carcinoma (HCC) at computed tomography (CT) and magnetic resonance (MR) imaging. MATERIALS AND METHODS The authors retrospectively reviewed the clinical, pathologic, and preoperative imaging findings in 31 patients with histologically proved fibrolamellar HCC. Dynamic contrast material-enhanced CT of the liver was performed in 31 patients, helical multiphase CT in 21, and MR imaging in 11. Complete resection was performed in 17 patients, and imaging-pathologic correlation was performed. RESULTS Large tumors (mean diameter, 13 cm) were depicted at CT and MR in all cases. At CT, the margins of the tumors were well defined in 24 (77%) of 31 cases calcifications were depicted in 21 (68%), a central scar in 22 (71%), and abdominal lymphadenopathy in 20 (65%). In 20 (80%) of 25 cases with hepatic arterial phase CT images, all tumors were heterogeneous and depicted areas of hypervascularity. At MR imaging, tumors were hypointense to liver on T1-weighted images (n = 11) and hyperintense to liver on T2-weighted images (n = 10). Calcification was not depicted on MR images, but a central scar was depicted as hypointense to surrounding tumor in nine cases. CONCLUSION CT and MR images demonstrate characteristic features that may allow confident diagnosis of fibrolamellar HCC.
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Affiliation(s)
- T Ichikawa
- Department of Radiology, University of Pittsburgh Medical Center, PA 15213, USA
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26
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Esquivel CO, Keeffe EB, Garcia G, Imperial JC, Millan MT, Monge H, So SK. Resection versus transplantation for hepatocellular carcinoma. J Gastroenterol Hepatol 1999; 14 Suppl:S37-41. [PMID: 10382637 DOI: 10.1046/j.1440-1746.1999.01901.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Hepatocellular carcinoma is responsible for more than 1 million deaths per year worldwide and thus remains a challenging medical problem. It causes few or no symptoms and the tumour frequently reaches an enormous size by the time of diagnosis in countries where screening is seldom used. It is generally resistant to commercially available anti-neoplastic agents and radiation therapy. The principal treatment continues to be resection, either partial or complete, with liver transplantation. However, less than one-third of patients are surgical candidates for either resection or transplantation at the time of clinical presentation. This review will address the results observed following resection or transplantation for hepatocellular carcinoma.
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Affiliation(s)
- C O Esquivel
- Department of Surgery, Stanford University School of Medicine, California, USA.
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27
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Epstein BE, Pajak TF, Haulk TL, Herpst JM, Order SE, Abrams RA. Metastatic nonresectable fibrolamellar hepatoma: prognostic features and natural history. Am J Clin Oncol 1999; 22:22-8. [PMID: 10025374 DOI: 10.1097/00000421-199902000-00006] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Fibrolamellar hepatoma has a clinical course distinct from that of typical histologic hepatocellular carcinoma. The clinical behavior and prognostic features of nonresectable metastatic fibrolamellar hepatoma have not previously been fully addressed and are the focus of this report. Retrospective chart review of all patients (n = 17) with nonresectable metastatic fibrolamellar hepatoma referred to the Johns Hopkins Oncology Center from 1985 through 1990 was carried out. All patients had hepatic parenchymal involvement and regional node metastases at the time of referral. Metastases were limited to regional nodes in four patients. The remaining patients had lung metastases (n = 4), peritoneal metastases (n = 5), or both (n = 4). To assess the impact of the fibrolamellar variant, characteristic-matched control patients with typical histologic hepatocellular carcinoma were obtained from the Radiation Therapy Oncology Group database. Actuarial median survival from treatment was 14 months in the patients with fibrolamellar hepatoma and 7.7 months in the patients with hepatocellular carcinoma (p < 0.001). Karnofsky performance status and hepatic tumor volume at time of referral were important prognostic features. Multimodality treatment included radiation therapy and radiolabelled antibody, cisplatin-based chemotherapy, or both; results are discussed. Thirteen patients died, nine of liver failure, three of metastatic disease, and one of sepsis. Fibrolamellar histologic type, liver function tests, tumor volume, and patient performance status were significant predictors of survival. The cause of death in fibrolamellar hepatoma differs considerably from that observed in typical histologic hepatocellular carcinoma in the United States. The techniques of treatment of this uncommon disease were modeled after advances in the multimodality treatment of hepatocellular carcinoma and are discussed. Median survival was 14 months in patients with metastatic nonresectable fibrolamellar hepatoma.
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Affiliation(s)
- B E Epstein
- Division of Radiation Oncology, Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8922, USA
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Wong WS, Patel SC, Cruz FS, Gala KV, Turner AF. Cryosurgery as a treatment for advanced stage hepatocellular carcinoma: results, complications, and alcohol ablation. Cancer 1998. [PMID: 9529018 DOI: 10.1002/(sici)1097-0142(19980401)82:7%3c1268::aid-cncr9%3e3.0.co;2-b] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The objective of this study was to investigate the use of cryosurgery and to determine whether there is a role for combined therapy with alcohol ablation in the treatment of patients with hepatocellular carcinoma. METHODS Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound-guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation was performed on those patients who were found to have residual tumor or recurrence after the cryosurgical procedure. RESULTS Of the 12 patients (9 males, 3 females) the size of the primary tumor ranged from 3-13 cm with average size of 7 cm in greatest dimension. Most patients had advanced disease according to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1 Stage II. Three patients had residual tumors after the cryosurgical procedure. The residual tumor was treated with alcohol ablation. The 1-year survival rate for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of 10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years and another patient with a 13-cm tumor was disease free for 2.5 years. Both of these patients had Stage IVA disease. CONCLUSIONS The authors found cryosurgery to be promising in the treatment of this extremely aggressive form of cancer, with the ability to prolong patient survival. Follow-up treatment with alcohol ablation is an important adjunct in treating residual tumor and controlling recurrences.
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Affiliation(s)
- W S Wong
- Cryosurgical Center of Southern California, Alhambra Hospital, 91801, USA
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Wong WS, Patel SC, Cruz FS, Gala KV, Turner AF. Cryosurgery as a treatment for advanced stage hepatocellular carcinoma: results, complications, and alcohol ablation. Cancer 1998; 82:1268-78. [PMID: 9529018 DOI: 10.1002/(sici)1097-0142(19980401)82:7<1268::aid-cncr9>3.0.co;2-b] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND The objective of this study was to investigate the use of cryosurgery and to determine whether there is a role for combined therapy with alcohol ablation in the treatment of patients with hepatocellular carcinoma. METHODS Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound-guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation was performed on those patients who were found to have residual tumor or recurrence after the cryosurgical procedure. RESULTS Of the 12 patients (9 males, 3 females) the size of the primary tumor ranged from 3-13 cm with average size of 7 cm in greatest dimension. Most patients had advanced disease according to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1 Stage II. Three patients had residual tumors after the cryosurgical procedure. The residual tumor was treated with alcohol ablation. The 1-year survival rate for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of 10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years and another patient with a 13-cm tumor was disease free for 2.5 years. Both of these patients had Stage IVA disease. CONCLUSIONS The authors found cryosurgery to be promising in the treatment of this extremely aggressive form of cancer, with the ability to prolong patient survival. Follow-up treatment with alcohol ablation is an important adjunct in treating residual tumor and controlling recurrences.
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Affiliation(s)
- W S Wong
- Cryosurgical Center of Southern California, Alhambra Hospital, 91801, USA
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30
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Zografos GN, Palmer S, Papastratis G, Habib NA. Aggressive surgical management of fibrolamellar hepatocellular carcinoma in puberty. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 1997; 23:570-2. [PMID: 9484935 DOI: 10.1016/s0748-7983(97)93493-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Extensive right hepatectomy and replacement of the invaded inferior vena cava were performed in a 14-year-old girl with fibrolamellar liver carcinoma. Despite the graft thrombosis the patient was discharged on the 50th post-operative day. After 3 years a solitary lung metastasis was resected and the patient remains with no sign of intra-abdominal or intrathoracic recurrence.
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Affiliation(s)
- G N Zografos
- Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London
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Abstract
This review summarizes the efficacy of the most common therapeutic option for hepatocellular carcinoma (HCC), partial hepatic resection, taking into account not only its antitumoural effect, but also its consequences on survival. Partial hepatic resection results in 5 year survival rates as high as 45% in more favourable subgroups having: small tumours, well-differentiated tumours, unifocal tumours, a lack of vascular invasions, an absence of cirrhosis, and the fibrolamellar variant. Resection has been limited primarily by low resectability rates and recurrent disease. However, surgical resection in the form of partial hepatectomy is the preferred treatment for HCC. The early detection of tumours by screening high-risk populations is crucial. During the 12 year period between 1983 and 1994, hepatic resections were carried out in 382 patients with HCC. One hundred and fifty-three (40%) had HCC smaller than 5 cm in diameter. There were 294 male and 88 female patients, with an average age of 52.3 years. Among them, 45% had liver cirrhosis and 73% were positive for hepatitis B surface antigen. Two hundred and eighteen (57%) were positive for hepatitis C virus circulating antibodies (since 1991). Operative mortality was 3.9%. The overall survival rates at 1, 3 and 5 years were 71, 52 and 46%, respectively. Sex, cirrhosis, Child's staging, surgical procedure, blood loss, pathological pattern, presence of capsule, surgical margin and DNA ploidy appeared to be factors not related to prognosis. However, alpha-fetoprotein level, size (whether less than or greater than 5 cm), and vascular invasion were factors which significantly affect survival.
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Affiliation(s)
- M F Chen
- Department of Surgery, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan
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32
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Farmer DG, Seu P, Swenson K, Economou J, Busuttil RW. Current and future treatment modalities for hepatocellular carcinoma. Clin Liver Dis 1997; 1:361-96, ix. [PMID: 15562574 DOI: 10.1016/s1089-3261(05)70276-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article reviews recent innovations in the treatment of Hepatocellular carcinoma (HCC), which, although a common malignancy, has often proved difficult to diagnose and treat effectively. The epidemiology and natural history of HCC are discussed, as well as treatments such as hepatic resection, liver transplantation, and cryosurgery, among others.
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Affiliation(s)
- D G Farmer
- Dumont-UCLA Liver Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, University of California, Los Angeles 90024-1749, USA
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Bower M, Newlands ES, Habib N. Fibrolamellar hepatocellular carcinoma responsive to platinum-based combination chemotherapy. Clin Oncol (R Coll Radiol) 1996; 8:331-3. [PMID: 8934055 DOI: 10.1016/s0936-6555(05)80724-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
A patient with advanced unresectable fibrolamellar hepatocellular carcinoma is reported, who was treated with cisplatinum, epirubicin and 5-fluorouracil combination chemotherapy. Tumour regression was achieved, enabling major debulking surgery to be performed. The patient remains in clinical remission 11 months after completing therapy.
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Affiliation(s)
- M Bower
- Charing Cross Hospital, London, UK
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34
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Lehnert T, Otto G, Herfarth C. Therapeutic modalities and prognostic factors for primary and secondary liver tumors. World J Surg 1995; 19:252-63. [PMID: 7754632 DOI: 10.1007/bf00308635] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
During the past decade considerable progress has been reported in the treatment of primary and secondary hepatic malignancies. Refined techniques in surgery, transplantation, radiotherapy, and chemotherapy apparently have made the delivery of treatment safer. At the same time improved understanding of tumor biology has been incorporated in treatment strategies. More recently specific and nonspecific, active and passive immunotherapies have excited wide interest, and information from the first randomized studies is now available. We review current treatment options for primary and secondary hepatic malignancies in an attempt to extract plausible treatment guidelines and to identify promising future directions.
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Affiliation(s)
- T Lehnert
- Department of Surgery, University of Heidelberg, Germany
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35
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Wahlstrom HE. Liver transplantation for hepatocellular carcinoma--is it worth it? Mayo Clin Proc 1994; 69:599-600. [PMID: 8189769 DOI: 10.1016/s0025-6196(12)62255-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Abstract
The aim of the paper is an accurate histologic description and illustration of those liver lesions that are usually summarized under the heading of "hepatic tumors and related subjects". For in some cases it may be unclear or at least controversial, whether the individual lesion is indeed an autonomous neoplasia or a malformation, regeneration or hyperplasia, the indifferent master term of neoformation is introduced, based on the fact that all of them are characterized by a cellular multiplication. According to common definitory practice the survey distinguishes between mesenchymal (angiomatous and non angiomatous) and epithelial neoformations. Among the latter hepatocellular and cholangiocellular types are distinguished, the criterium for differentiation being a phenomenological one, which is by no means identical with a histogenetical statement. The definition of subgroups mostly adheres to current nomenclatory usage; only occasionally--in the group of endothelial tumors--a novel term is employed, in view of brevity and coordination with the overall system of neoformations.
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37
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Abstract
OBJECTIVE This study evaluated the currently available treatment modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA One of the most common tumors worldwide, HCC has several known risk factors. Untreated HCC typically has a dismal prognosis. Early detection remains the key to successful treatment of this malignancy. Surgical resection has been the mainstay of treatment for HCC, but newer modalities have been recently introduced. METHODS The authors evaluated the treatment modalities for HCC. RESULTS Surgical resection affords 5-year survival rates as high as 45% with more favorable subgroups having 1) small tumors, 2) well-differentiated tumors, 3) unifocal tumors, 4) lack of vascular invasion, 5) absence of cirrhosis, and 6) the fibrolamellar variant (FL-HCC). Resection has been limited primarily by low resectability rates and recurrent disease. Newer therapeutic modalities that appear the most promising are transarterial chemoembolization and percutaneous ethanol injection. Neither therapy has been evaluated in a prospective randomized manner. Combination chemotherapy and surgical intervention may provide the best results, but randomized controlled trials with long-term follow-up are needed. As single-treatment modalities, radiation therapy, intravenous chemotherapy, intra-arterial chemotherapy, and immunotherapy play limited palliative roles. CONCLUSIONS Surgical resection in the form of partial or total hepatectomy is the preferred treatment for HCC. The early detection of tumors by screening high-risk populations is crucial. Randomized trials of combinations of chemotherapy and surgical resection are needed to demonstrate their potential utility for treatment.
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Affiliation(s)
- D G Farmer
- Department of Surgery, Dumont-UCLA Liver Transplant Center
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38
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Affiliation(s)
- M Colombo
- Institute of Medicine, University of Milan, Italy
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39
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Pichlmayr R, Weimann A, Steinhoff G, Ringe B. Liver transplantation for hepatocellular carcinoma: clinical results and future aspects. Cancer Chemother Pharmacol 1992; 31 Suppl:S157-61. [PMID: 1333902 DOI: 10.1007/bf00687127] [Citation(s) in RCA: 30] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The treatment of unresectable hepatocellular carcinoma (HCC) by liver transplantation remains controversial. In our series, the 5-year survival value for 87 patients who underwent transplantations between 1972 and 1990 was 19.6%. There was no difference in the long-term survival of patients who had underlying cirrhosis and those who did not. In patients with early-stage tumors the long-term prognosis was improved, the 5-year survival in stage II disease being 55.6% according to UICC criteria. Even in some cases of more advanced tumour stage, good long-term results were obtained. In a review of the recent literature, we evaluated prognostic factors to work out criteria for a more differentiated indication for liver transplantation. Resection of increased radicality--which will keep its place as the therapy of choice--and transplantation should be performed complementarily. Further developments will reveal the value of multimodal therapeutic strategies, including chemo-embolisation, chemotherapy and immunotherapy.
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Affiliation(s)
- R Pichlmayr
- Klinik für Abdominal- and Transplantationschirurgie, Medizinische Hochschule Hannover, Federal Republic of Germany
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40
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Ringe B, Pichlmayr R, Wittekind C, Tusch G. Surgical treatment of hepatocellular carcinoma: experience with liver resection and transplantation in 198 patients. World J Surg 1991; 15:270-85. [PMID: 1851588 DOI: 10.1007/bf01659064] [Citation(s) in RCA: 418] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Surgical therapy offers the only chance for long-term cure of patients with hepatocellular carcinoma. The role of partial and total hepatectomy with subsequent liver replacement was analyzed in a consecutive series of 198 patients. It was the aim of this study to compare both treatment modalities on the basis of various clinicopathological prognostic factors including the TNM system of pathological classification. One hundred thirty-one resections and 61 transplantations were performed for the following histological diagnoses: hepatocellular carcinoma without coexisting liver disease (86) or associated with various hepatic abnormalities (79), fibrolamellar carcinoma (19), and mixed hepatocholangiocellular carcinoma (8). Overall actuarial survival rates at 5 years were 35.8% following resection and 15.2% after transplantation, respectively. For partial hepatectomy, factors significantly associated with improved long-term outcome were: age 30-50 years, hepatocellular carcinoma without coexisting liver disease, fibrolamellar carcinoma, solitary tumor, unilobar location, absence of vascular invasion, portal vein thrombosis or extrahepatic spread, primary tumor categories pT 2/3, stage groups II/III, and curative operation (R0). Regarding total hepatectomy, the corresponding figures were: pT2, absence of portal vein thrombosis or extrahepatic spread (negative regional lymph nodes, no distant metastases), stage group II, and curative surgery. It could be clearly shown by uni- and multivariate analyses that the pTNM classification is of clinical value regarding the assessment of prognostic significance after resection and transplantation. A group of 13 patients had secondary resection (8) or transplantation (6) for intrahepatic tumor recurrence. Whereas in all resected patients cancer recurred again, 5 of 6 transplant recipients are alive and disease-free at 12-40 months. The results of this study demonstrate that liver resection is the treatment of choice for primary liver cancer while transplantation may be indicated, especially in cases of nonresectable or recurrent lesions. Thus, the therapeutic spectrum for hepatocellular carcinoma should include both partial and total hepatectomy, being integrated into one common concept.
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Affiliation(s)
- B Ringe
- Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Federal Republic of Germany
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41
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Stillwagon GB, Order SE, Guse C, Leibel SA, Asbell SO, Klein JL, Leichner PK. Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01. Int J Radiat Oncol Biol Phys 1991; 20:65-71. [PMID: 1847127 DOI: 10.1016/0360-3016(91)90139-u] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The Radiation Therapy Oncology Group (RTOG) conducted a Phase I/II study in hepatocellular cancer that closed on September 9, 1987 and some results presented previously. Here, 17 patient characteristics are evaluated to identify any of prognostic significance. Two hundred sixteen patients were entered and 198 (74% with metastases and/or previous chemotherapy) were evaluable. Treatment began with an induction regimen of external beam radiotherapy to the liver (21.0 Gy, 3.0 Gy/Fx, 10 MV photons, 4 days per week) with low-dose chemotherapy (5-Fluorouracil (FU), 500 mg, i.v.; Doxorubicin, 15 mg, i.v.) on treatment Days 1, 3, 5 and 7. In the later stages of these studies, 56 patients received external beam radiotherapy as hyperfractionated treatment (1.2 Gy twice daily, 4 hours separation, 5 days per week, 24.0 Gy total) with similar chemotherapy. One month following induction therapy, cycles of radiolabeled antibody therapy were given every 2 months. Each cycle was derived from a different species of animal and consisted of 30 mCi I-131 antiferritin, Day 0, and 20 mCi, Day 5. On Day -1, 5-FU, 500 mg, and Adriamycin, 15 mg, were administered. The overall median survival for the entire group, including previously treated patients, was 4.9 months. The median survival for alpha-fetoprotein (AFP) - patients not previously treated was 10.5 months. Median survival for all AFP - patients was 8.5 months and for all AFP + patients was 4.6 months (p = 0.006). Of the 17 pretreatment characteristics investigated for prognostic value Karnofsky Performance Score (KPS) (80-100 vs. less than 80) (p = 0.0001), presence/absence of ascites (p = 0.0002), bilirubin level (less than 1.5 vs. greater than or equal to 1.5) (p = 0.018), SGOT (less than or equal to 35 vs. greater than 35) (p = 0.001); alkaline phosphatase (less than or equal to 95 vs. greater than 95) (p = 0.008) were found to be significant independently using a multivariant regression model. The relative risk of dying for the unfavorable component of each of these characteristics was 2.2, 2.0, 1.5, 1.9 and 1.7, respectively. Good and poor prognostic groups were then defined and compared to a similar patient population (RTOG study 83-19) with confirmation of the validity of the model. When stratification for these overpowering clinical factors was incorporated, AFP status was again significant with a relative death rate 1.80 times higher for AFP+ patients. Our recommendations for structuring future prospective randomized trials are discussed and include stratification by AFP status.
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Calvet X, Bruix J, Ginés P, Bru C, Solé M, Vilana R, Rodés J. Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. Hepatology 1990; 12:753-60. [PMID: 2170267 DOI: 10.1002/hep.1840120422] [Citation(s) in RCA: 169] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials.
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Affiliation(s)
- X Calvet
- Liver Unit, Hospital Clínic i Provincial, Barcelona, Spain
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43
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Abstract
Hepatic metastases represent a common site of dissemination for a number of primary malignancies related in part to the dual blood supply, large blood flow, and receptive environment of the hepatic parenchyma. Although this review focuses on regional therapy, we have included sections on systemic therapy to better interpret the results with intrahepatic therapy. We will also discuss the efficiency of hepatic arterial ligation, embolization, and radiotherapy of hepatic metastases. Primary gastrointestinal neoplasms are particularly prone to produce hepatic metastases. Because colorectal carcinoma metastasizes to the liver in up to 70% of patients with advanced disease, the treatment of hepatic metastases is a relevant topic. We will discuss the systemic and regional therapy of colorectal, gastric, and gallbladder cancers. Breast carcinoma and malignant melanoma frequently metastasize to the liver, and we have described systemic and regional treatments of these diseases. Because sarcomas are often treated by regional therapy, we have included a section on the treatment of hepatic sarcomas. Neuroendocrine tumors (carcinoid and islet cell), although often slow growing, frequently metastasize to the liver and then cause symptomatic problems. Much of the work done with embolization and hepatic ligation in the treatment of hepatic metastases has been performed in neuroendocrine tumors, and these studies, as well as the systemic and regional chemotherapy of hepatic metastases, will be described. The last section concerns the treatment of hepatocellular carcinoma. We have outlined the staging systems used. We then detail the results of systemic and intrahepatic therapy, embolization, and hepatic ligation in the treatment of hepatocellular carcinoma. Because hepatic metastases are a frequent problem, many patients are available for clinical investigation. It is hoped that newer strategies for the treatment of liver metastases will lead to higher response rates and perhaps control of local disease. These therapeutic approaches may also give us leads to the treatment of systemic disease.
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Affiliation(s)
- N Kemeny
- Gastrointestinal Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, New York
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