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1
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Dutta S, Chandra A, Ganai S, Chakraborty U, Pm S. Metastasis to the skull base involving the sphenoid and cavernous sinus in hepatocellular carcinoma. J R Coll Physicians Edinb 2024; 54:221-224. [PMID: 39136264 DOI: 10.1177/14782715241270368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, among which around 18-64% metastasize, most frequently to lungs, regional lymph nodes and adrenal glands. Metastasis of HCC to the central nervous system represents a rare yet clinically significant phenomenon, often presenting diagnostic and therapeutic challenges. In this case report, we document a 35-year-old male who presented with a secondary headache and right ophthalmoplegia attributable to metastatic deposits secondary to HCC infiltrating the cavernous sinus and superior orbital fissure. Despite therapeutic interventions including local palliative radiotherapy and sorafenib, the patient succumbed to acute liver failure after 9 months. This case highlights the aggressive potential of HCC to involve the central nervous system and the importance of heightened clinical suspicion for early diagnosis and intervention in such rare but clinically impactful scenarios.
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Affiliation(s)
- Sukanta Dutta
- Department of Internal Medicine, Midnapore Medical College and Hospital, Midnapore, WB, India
| | - Atanu Chandra
- Department of Internal Medicine, RG Kar Medical College and Hospital, Kolkata, India
| | - Saikot Ganai
- Department of Neurology, Burdwan Medical College and Hospital, Burdwan, WB, India
| | - Uddalak Chakraborty
- Department of Neurology, Bangur Institute of Neurosciences, IPGMER and SSKM, Kolkata, India
| | - Sumesh Pm
- Department of Internal Medicine, Midnapore Medical College and Hospital, Midnapore, WB, India
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2
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Rauschenbach L, Kolbe P, Engel A, Ahmadipour Y, Oppong MD, Santos AN, Kebir S, Dobersalske C, Scheffler B, Deuschl C, Dammann P, Wrede KH, Sure U, Jabbarli R. Predictors and surgical outcome of hemorrhagic metastatic brain malignancies. J Neurooncol 2024; 169:165-173. [PMID: 38801490 PMCID: PMC11269501 DOI: 10.1007/s11060-024-04714-2] [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: 03/27/2024] [Accepted: 05/11/2024] [Indexed: 05/29/2024]
Abstract
PURPOSE Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. METHODS A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. RESULTS A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). CONCLUSION This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.
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Affiliation(s)
- Laurèl Rauschenbach
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
- DKFZ Division of Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany.
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany.
| | - Pia Kolbe
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Adrian Engel
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Yahya Ahmadipour
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Marvin Darkwah Oppong
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Alejandro N Santos
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Sied Kebir
- DKFZ Division of Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
- Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, Essen, Germany
| | - Celia Dobersalske
- DKFZ Division of Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, University of Duisburg-Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Björn Scheffler
- DKFZ Division of Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany
- German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, University of Duisburg-Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Cornelius Deuschl
- Institute for Diagnostic and Interventional Radiology, University Hospital Essen, Essen, Germany
| | - Philipp Dammann
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Karsten H Wrede
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Ulrich Sure
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
| | - Ramazan Jabbarli
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
- Center for Translational Neuroscience and Behavioral Science (C-TNBS), University of Duisburg-Essen, Essen, Germany
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3
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Knapp J, Babu H, Benjamin S, Shapiro A. Hepatocellular carcinoma metastatic to the pituitary gland without an identifiable primary lesion. Radiol Case Rep 2024; 19:1263-1267. [PMID: 38292788 PMCID: PMC10825538 DOI: 10.1016/j.radcr.2023.12.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 12/02/2023] [Accepted: 12/18/2023] [Indexed: 02/01/2024] Open
Abstract
Hepatocellular carcinoma is one of the most common malignancies worldwide. However, brain metastases from this cancer are incredibly rare. While the hepatocellular carcinoma mortality rate in the United States has been increasing, hepatocellular carcinoma is rare among patients without underlying liver disease. Here we present a patient with a history of left optic nerve meningioma treated with stereotactic radiosurgery who presented with acute vision loss. Magnetic resonance imaging revealed an enhancing mass lesion in the region of the sella turcica. Neurosurgical histopathology revealed a metastatic lesion consistent with hepatocellular carcinoma. Systemic workup failed to identify a primary liver lesion.
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Affiliation(s)
- Jacquelyn Knapp
- Department of Radiation Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Harish Babu
- Department of Neurosurgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Sam Benjamin
- Department of Medical Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Anna Shapiro
- Department of Radiation Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
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Signorelli F, Fraschetti F, Benato A, Visocchi M. Repeated surgery for hemorrhagic brain metastases from hepatocellular carcinoma: palliation or effective part of a multimodal treatment? A case-based approach. Br J Neurosurg 2023; 37:1770-1773. [PMID: 33759662 DOI: 10.1080/02688697.2021.1903394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 03/11/2021] [Indexed: 10/21/2022]
Abstract
Brain metastases from hepatocellular carcinoma (HCCBM) are encountered very rarely in clinical practice, especially in western countries. Only a minority of patients undergoes resective surgery, as clinical picture is usually complex and presentation is often catastrophic with intra-cerebral hemorrhage (ICH). Neurosurgical intervention can be not only life-saving but may also alleviate significantly the burden of symptoms. We present the case of a patient with six metachronous hemorrhagic HCCBM in which emergent surgery extended survival by 9 months, of which seven spent in near-normal life quality, stressing the role of neurosurgery in the evaluation of HCCBM patients.
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Affiliation(s)
- Francesco Signorelli
- Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy
| | - Flavia Fraschetti
- Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy
| | - Alberto Benato
- Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy
| | - Massimiliano Visocchi
- Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy
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Chaudhry H, Sohal A, Iqbal H, Chaudhary U, Roytman M. Unusual sites of hepatocellular carcinoma metastasis: Case report. SAGE Open Med Case Rep 2023; 11:2050313X231211709. [PMID: 38022862 PMCID: PMC10647942 DOI: 10.1177/2050313x231211709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Hepatocellular carcinoma is an increasingly frequent cause of cancer-related death. The majority of patients with hepatocellular carcinoma are asymptomatic. In rare cases, patients may present with symptoms of extrahepatic metastases. Early identification can lead to timely treatment and prevent poor outcomes. We report three cases of patients with hepatocellular carcinoma with unusual sites of metastasis, including clival, mandible, and cardiac involvement.
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Affiliation(s)
- Hunza Chaudhry
- Department of Internal Medicine, University of California San Francisco—Fresno, Fresno, CA, USA
| | | | - Humzah Iqbal
- Department of Internal Medicine, University of California San Francisco—Fresno, Fresno, CA, USA
| | - Uzair Chaudhary
- Department of Hematology and Oncology, University of California San Francisco—Fresno, Fresno, CA, USA
| | - Marina Roytman
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco—Fresno, Fresno, CA, USA
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6
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Zakaria R, Mubarak F, Khandwala K, Memon A. Skull base metastasis as initial presentation of hepatocellular carcinoma. Surg Neurol Int 2023; 14:297. [PMID: 37680914 PMCID: PMC10481823 DOI: 10.25259/sni_166_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 07/26/2023] [Indexed: 09/09/2023] Open
Abstract
Background Intracranial metastatic deposits due to hepatocellular carcinoma (HCC) are rare. Only a few cases are reported in the literature. These may be more likely to come to clinical attention than extrahepatic metastases in other sites since they often produce symptoms that necessitate neurosurgical intervention. Case Description We report a case of a 53-year-old male with biopsy-proven intracranial skull base metastasis from HCC as an unusual initial presentation of the disease and review the relevant literature on this entity. Conclusion Intracranial metastasis of HCC should be included in the differential diagnosis of rapidly growing metastatic lesions in unusual locations, particularly in chronic liver disease and hepatitis B surface antigen-positive or hepatitis C patients.
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Affiliation(s)
- Raima Zakaria
- Department of Radiology, Aga Khan University, Karachi, Pakistan
| | - Fatima Mubarak
- Department of Radiology, Aga Khan University, Karachi, Pakistan
| | | | - Aisha Memon
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
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7
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Thida C, Pokhrel A, Sun L, Wu R, Jaswani V, Wang JC. Hemorrhagic Brain Metastasis as an Initial Presentation of Hepatocellular Carcinoma in a Patient With Alcohol-Related Liver Cirrhosis: A Case Report and Review of Literature. J Investig Med High Impact Case Rep 2022; 10:23247096221117788. [PMID: 35975720 PMCID: PMC9527531 DOI: 10.1177/23247096221117788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer.
Although it usually presents as a liver mass, rarely HCC can have an initial
presentation at an extrahepatic site before the diagnosis of the primary lesion
in the liver. Even rarely was that brain metastasis as initial extrahepatic
presentations. Furthermore, the initial presentation of HCC as brain metastases
has been with most cases being secondary to hepatitis-related hepatoma. In this
case report, we are presenting a rare and unusual case of hemorrhagic cerebral
metastasis as an initial extrahepatic presentation of an alcohol-related
hepatoma. Our case is the second case in the English literature that has been
presented in such a way. Due to the uncommonness of presentation, there can be
diagnostic dilemmas and delay in treatment. Therefore, a high level of suspicion
is needed in the high-risk patients of HCC who present with unexplained or new
neurological signs and symptoms. More exploration is warranted for clinical
research and treatment guidelines for brain metastases of HCC to help improve
survival and quality of life.
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Affiliation(s)
- Chan Thida
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Akriti Pokhrel
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Lishi Sun
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Richard Wu
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Vijay Jaswani
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Jen C. Wang
- Brookdale University Hospital Medical Center, Brooklyn, NY, USA
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8
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Carbohydrate antigen-125, calcium, and hemoglobin as predictive clinical indicator for ocular metastasis in male liver cancer patients. Biosci Rep 2021; 40:222102. [PMID: 32090248 PMCID: PMC7040464 DOI: 10.1042/bsr20194405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 12/13/2022] Open
Abstract
Background Primary liver cancer (PLC) is a common type of cancer among men worldwide. Little is known regarding the relationship of liver cancer with ocular metastasis (OM). Drinking has been also reported to be related not only to the occurrence of liver cancer but also to the causes of some ocular lesions. Purpose A diagnostic standard for the levels of serum biomarkers associated with OM derived from liver cancer in men is urgently needed. Material and methods We examined the association between OM in liver cancer and its serum biomarkers. A total of 1254 male patients with liver cancer were recruited in this retrospective study between July 2002 and December 2012. We assessed the relationship between drinking preference and OM in male patients with liver cancer, and aimed to identify an independent prognostic factor or establish a quantitative indicator for OM. Results By assessing the potential indicators, carbohydrate antigen-125 (CA-125), calcium, and hemoglobin (Hb) were found to be most valuable in the diagnosis of OM in male patients with liver cancer. Conclusion CA-125, calcium, and Hb are independent risk factors of OM in patients with liver cancer who consume alcohol.
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Durable Complete Response of Brain Metastasis From Hepatocellular Carcinoma On Treatment With Nivolumab and Radiation Treatment. Am J Gastroenterol 2020; 115:2114-2116. [PMID: 32852335 DOI: 10.14309/ajg.0000000000000800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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10
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Kumar H, Kinra P, Malik A. Metastatic hepatocellular carcinoma in brain masquerading as rhabdoid CNS tumor - A case report. INDIAN J PATHOL MICR 2020; 63:145-147. [PMID: 32031150 DOI: 10.4103/ijpm.ijpm_86_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Harish Kumar
- Departmentof Pathology, AFMC, Pune, Maharashtra, India
| | - Prateek Kinra
- Department of (Path) and GI Pathologist, AFMC, Pune, Maharashtra, India
| | - Ajay Malik
- Departmentof Pathology, AFMC, Pune, Maharashtra, India
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11
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Liu Y, Hao S, Ji N, Wang J, Zhang L. Combination of Anti-Programmed Death 1 Therapy and Apatinib for a Patient with Hepatocellular Carcinoma and Brain Metastasis: Case Report and Literature Review. World Neurosurg 2020; 143:114-117. [PMID: 32534262 DOI: 10.1016/j.wneu.2020.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Brain metastasis is rare in patients with hepatocellular carcinoma (HCC). The combination of an anti-programmed death 1 inhibitor and an anti-vascular endothelial growth factor drug provides therapeutic opportunities for refractory patients. So far, there are no data on the efficacy of these combined therapies for patients with HCC brain metastasis. CASE DESCRIPTION HCC brain metastasis was diagnosed in a 31-year-old man. First, he underwent left liver resection and cholecystectomy and recovered well postoperatively. The postoperative pathologic findings were consistent with HCC. Approximately 2 years later, he presented with persistent headache and underwent magnetic resonance imaging, which revealed a lesion in the left parietal lobe. Anti-programmed death 1 and anti-vascular endothelial growth factor drugs were administered in combination, but the lesion did not shrink after the combined treatment on repeat magnetic resonance imaging. Therefore, surgical removal of the brain lesion was performed 2 months later. The postoperative pathologic results showed coagulative necrosis. CONCLUSIONS This case report highlights the efficacy of toripalimab and apatinib in the management of brain metastasis from HCC.
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Affiliation(s)
- Yufei Liu
- Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Neurosurgical Department, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Shuyu Hao
- Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Nan Ji
- Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Jiangfei Wang
- Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Liwei Zhang
- Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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Abstract
Due to the aggressive nature of hepatocellular carcinoma (HCC), most patients succumb to disease before any distant metastasis, such as to the central nervous system (CNS), can occur. Thus only a handful of cases of metastasis to the skull base have been described. After a thorough review of the available literature published since 1950, we report the sixth case of HCC metastasis to the clivus. In this case, a 65-year-old man with a history of melanoma presented with sudden onset of right-sided headache and complete ophthalmoplegia of the right eye for one month. MRI of the brain with and without contrast demonstrated a homogeneously enhancing lesion involving the clivus with evidence of invasion into the right cavernous sinus. Through further body imaging, he was found to have an infiltrative lesion in the left hepatic lobe and underwent an ultrasound-guided biopsy of said lesion that was proven to be well-differentiated hepatocellular carcinoma. An endonasal endoscopic biopsy of his clival lesion was performed and the final pathology was consistent with a metastatic HCC. This case demonstrates the impact of obtaining a surgical specimen of clival tumors to confirm the suspected diagnosis, as well as to perform molecular studies that can drive post-operative decision-making and prognosis. As in this case, the final diagnosis altered treatment plans from that of melanoma, with systemic chemotherapy and radiosurgery, to stereotactic radiosurgery and intrahepatic radioembolization.
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Affiliation(s)
| | - Yasir R Khan
- Neurosurgery, Desert Regional Medical Center, Palm Springs, USA
| | - Danny Blais
- Neurosurgery, Desert Regional Medical Center, Palm Springs, USA
| | - Bandana Mahato
- Neurosurgery, Desert Regional Medical Center, Palm Springs, USA
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Nam HC, Sung PS, Song DS, Kwon JH, Nam SW, Yoon DJ, Jang JW, Choi JY, Yoon SK, Moon SW, Jang HS, Park JS, Jeun SS, Hong YK, Bae SH. Control of intracranial disease is associated with improved survival in patients with brain metastasis from hepatocellular carcinoma. Int J Clin Oncol 2019; 24:666-676. [PMID: 30788672 DOI: 10.1007/s10147-019-01407-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 01/22/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC. METHODS About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified. RESULTS The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child-Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child-Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively). CONCLUSION Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients.
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Affiliation(s)
- Hee Chul Nam
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Do Seon Song
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jung Hyun Kwon
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Internal Medicine, College of Medicine, Incheon St. Mary's hospital, The Catholic University of Korea, Seoul, South Korea
| | - Soon Woo Nam
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Internal Medicine, College of Medicine, Incheon St. Mary's hospital, The Catholic University of Korea, Seoul, South Korea
| | - Dong Jin Yoon
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Jeong Won Jang
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Seok Whan Moon
- Department of Thoracic and Cardiovascular Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Jae-Sung Park
- Department of Neurosurgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Sin-Soo Jeun
- Department of Neurosurgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Yong-Kil Hong
- Department of Neurosurgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Si Hyun Bae
- The Catholic Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- Department of Internal Medicine, College of Medicine, St. Paul's Hospital, The Catholic University of Korea, Seoul, South Korea.
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Predictive value of a nomogram for hepatocellular carcinoma with brain metastasis at initial diagnosis: A population-based study. PLoS One 2019; 14:e0209293. [PMID: 30601858 PMCID: PMC6314620 DOI: 10.1371/journal.pone.0209293] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 12/03/2018] [Indexed: 12/17/2022] Open
Abstract
Background Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of hepatocellular carcinoma (HCC) are lacking. The aim of this study was to characterize the incidence proportion and survival of newly diagnosed hepatocellular carcinoma with brain metastases (HCCBM). Materials and methods Data from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2014 was evaluated. Patients with HCCBM were included. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and prognostic factors of overall survival (OS). We also built a nomogram based on Cox model to predict prognosis for HCCBM patients. Results We identified 97 patients with brain metastases at the time of diagnosis of HCC, representing 0.33% of the entire cohort. Logistic regression showed patients with bone or lung metastases had greater odds of having brain metastases at diagnosis. Median OS for HCCBM was 2.40 months. Cox regression revealed unmarried and bone metastases patients suffered significantly shorter survival time. A nomogram was developed with internal validation concordance index of 0.639. Conclusions This study provided population-based estimates of the incidence and prognosis for HCCBM patients. The nomogram could be a convenient individualized predictive tool for prognosis.
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Bevacizumab and risk of intracranial hemorrhage in patients with brain metastases: a meta-analysis. J Neurooncol 2017; 137:49-56. [PMID: 29170906 PMCID: PMC5846997 DOI: 10.1007/s11060-017-2693-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Accepted: 11/18/2017] [Indexed: 12/25/2022]
Abstract
Administration of bevacizumab to patients with brain metastases (BM) is controversial due to concerns about the increased risk of intracranial hemorrhage (ICH). This meta-analysis assessed whether the risk of ICH increases in BM patients receiving treatments that contain bevacizumab versus without. PubMed, Embase, Cochrane Library and annual meeting abstracts of the American Society of Clinical Oncology up to 13 November 2016 were searched for studies that referred to ICH complications due to bevacizumab in patients with BM. Eight studies involving 8713 patients were included in this analysis. Compared with the control arm without bevacizumab, the bevacizumab treatment arm did not exhibit a significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI) 0.69–2.09; P = 0.53]. Subgroup analyses with retrospective studies showed a similar result, although subgroup analyses with prospective studies failed. This meta-analysis revealed that bevacizumab does not significantly increase the risk of ICH in solid tumor patients with BM.
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Wang S, Wang A, Lin J, Xie Y, Wu L, Huang H, Bian J, Yang X, Wan X, Zhao H, Huang J. Brain metastases from hepatocellular carcinoma: recent advances and future avenues. Oncotarget 2017; 8:25814-25829. [PMID: 28445959 PMCID: PMC5421971 DOI: 10.18632/oncotarget.15730] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 02/07/2017] [Indexed: 12/25/2022] Open
Abstract
The incidence of brain metastases from hepatocellular carcinoma (BMHCC) is becoming more frequent than that of the past as a result of prolonged survival of patients with HCC. Compared with brain metastases from other types of cancer, BMHCC tends to exhibit a high incidence of intracerebral hemorrhage (ICH) and poor liver function. Unfortunately, the prognosis is extremely poor for patients with BMHCC owing to the limited treatment selection. Currently, optimal treatment requires multidisciplinary approaches including surgery, whole-brain radiation therapy and stereotactic radiosurgery. Besides these traditional approaches, novel treatments such as target therapy and immunotherapy provide an opportunity to improve the survival of these patients. This review provides an overview of the incidence, characteristics, prognosis, and current and potential future management strategies for BMHCC.
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Affiliation(s)
- Shanshan Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Anqiang Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianzhen Lin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Xie
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liangcai Wu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaobo Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xueshuai Wan
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Center of Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiefu Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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17
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Kamimura K, Kobayashi Y, Takahashi Y, Abe H, Kumaki D, Yokoo T, Kamimura H, Sakai N, Sakamaki A, Abe S, Takamura M, Kawai H, Yamagiwa S, Terai S. Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment. Cancer Biol Ther 2017; 18:79-84. [PMID: 28045618 PMCID: PMC5362986 DOI: 10.1080/15384047.2016.1276134] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 12/12/2016] [Accepted: 12/18/2016] [Indexed: 12/17/2022] Open
Abstract
Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.
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Affiliation(s)
- Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Yuji Kobayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Yoshifumi Takahashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Daisuke Kumaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Norihiro Sakai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Satoshi Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachido-ri, Chuo-ku, Niigata, Japan
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18
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Chan V, Sahgal A, Egeto P, Schweizer T, Das S. Incidence of seizure in adult patients with intracranial metastatic disease. J Neurooncol 2016; 131:619-624. [PMID: 27878505 DOI: 10.1007/s11060-016-2335-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 11/12/2016] [Indexed: 12/11/2022]
Abstract
Seizures have considerable impact on a patient's quality of life. While guidelines have been articulated to direct clinicians in their management of patients with IMD who suffer from seizure, there have been few attempts to identify the seizure rate in IMD and to determine which primary cancers may be associated with an increased seizure incidence. To determine the incidence of seizure in patients with IMD. A systematic review on seizure incidence in patients with IMD from the magnetic resonance imaging (MRI) era was performed. Articles published between January 2000 and July 2014 with thirty or more consecutive adult patients were included in this study. Seizure rate was calculated using a pooled data analysis. Differences between observed and expected seizure rates between primary tumour sites were examined using the Chi square statistic and adjusted standardized residuals. The systematic search produced 18 relevant studies, with a total study population of 2012 patients. 14.6% (n = 294) had seizures. There was a significant association between primary tumour site and seizure rates. The seizure rate in patients with primary melanoma tumours was significantly greater than expected (z = 2.7; p = .006). The seizure rate in patients with primary prostate tumours was significantly lower than expected (z = -2.6; p = .008). Patients with intracranial metastasis are at significant risk for developing seizure, though at a significantly lower incidence than was estimated by studies performed during the CT era. Seizure rates appear to be greater in certain primary tumours, such as melanoma.
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Affiliation(s)
- Vivien Chan
- Keenan Research Centre, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.,University of Toronto, Toronto, ON, Canada
| | - Arjun Sahgal
- Department of Radiation Oncology, Sunnybrook Hospital, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada
| | - Peter Egeto
- Keenan Research Centre, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.,University of Toronto, Toronto, ON, Canada
| | - Tom Schweizer
- Faculty of Medicine, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada
| | - Sunit Das
- Keenan Research Centre, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. .,Division of Neurosurgery, Department of Surgery, Toronto, ON, Canada. .,University of Toronto, Toronto, ON, Canada.
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Yamakawa Y, Moriguchi M, Aramaki T, Mitsuya K, Asakura K, Sawada A, Endo M, Nakasu Y. Brain metastasis from hepatocellular carcinoma: The impact of radiotherapy on control of intracranial hemorrhage. Hepatol Res 2015; 45:1071-5. [PMID: 25470452 DOI: 10.1111/hepr.12457] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Revised: 11/26/2014] [Accepted: 11/27/2014] [Indexed: 12/22/2022]
Abstract
AIM Brain metastasis from hepatocellular carcinoma (HCC) is rare and causes devastating outcomes with intracranial hemorrhage. We retrospectively analyzed the impact of radiotherapy in preventing hemorrhagic events among patients with brain metastasis from HCC. METHODS Patients who underwent treatment for brain metastasis from HCC at our cancer center between January 2003 and December 2012 were identified from a prospectively compiled hospital database. Clinical characteristics were analyzed in patients with and without radiotherapy. RESULTS Fifteen HCC patients with brain metastasis from HCC were classified into two groups: 11 patients underwent radiotherapy (group R) and four patients received best supportive care without radiotherapy (group N). Six patients (54.5%) in group R and four patients (100%) in group N showed intracranial hemorrhage at presentation of brain metastasis. No patients in group R experienced intracranial hemorrhage during follow up, although two patients in group N did. Median overall survival was 22.4 weeks (range, 5.42-69.1) in group R and 2.24 weeks (range, 1.0-15.4) in group N. CONCLUSION For patients with brain metastasis from HCC, radiotherapy appears useful for controlling brain lesions, preventing intracranial hemorrhage and improving survival. Radiotherapy may contribute to control of intracranial tumor and prevention of intracranial hemorrhage for selected patients with brain metastasis from HCC.
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Affiliation(s)
- Yushi Yamakawa
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Michihisa Moriguchi
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Takeshi Aramaki
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Koichi Mitsuya
- Division of Neurosurgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Koiku Asakura
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Akihiro Sawada
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Masahiro Endo
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Yoko Nakasu
- Division of Neurosurgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
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20
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Park Y, Kim KS, Kim K, Chie EK, Kim JH, Kim JS, Kim TH, Kim DY, Jang WI, Kim MS, Koo TR, Chang AR. Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study. J Neurooncol 2015; 125:377-83. [PMID: 26342711 DOI: 10.1007/s11060-015-1926-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 08/31/2015] [Indexed: 12/30/2022]
Abstract
The incidence of brain metastasis from hepatocellular carcinoma (HCC) is increasing because of the improved survival outcome of HCC patients, but the prognosis of these patients is extremely poor. HCC patients with brain metastasis were investigated to identify their prognostic factors for overall survival. Patients with brain metastasis from HCC who had been treated with whole-brain radiotherapy (WBRT) in five hospitals were enrolled in the study. The medical records of the patients were reviewed, and the clinical factors were analyzed to identify the prognostic factors for overall survival. Of the total of 97 patients who were enrolled in the study, 83 were male and the median age at the brain metastases was 56.6 years. Motor weakness (43.3 %) and headache (41.2 %) were common presenting symptoms. The median AFP level was 4180 ng/ml, and 81 patients were assessed as belonging to Child-Pugh classification A upon the diagnosis of brain metastasis. WBRT alone in 71 patients, surgery or radiosurgery combined with WBRT as the adjuvant setting in 18 patients, and WBRT as salvage treatment in 8 patients were performed. The median overall survival of the patients was 3.5 months. In the multivariate analysis, the ECOG performance status (PS), Child-Pugh classification, AFP, and treatment aim showed significant association with the overall survival of the patients. Based on these factors, a nomogram predicting the prognosis was developed. The concordance index of the nomogram was 0.74, and the prediction was well calibrated. In conclusion, the survival outcome of patients with brain metastasis from HCC can be predicted with the nomogram constructed from the ECOG PS, Child-Pugh classification, AFP, and treatment aim.
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Affiliation(s)
- Younghee Park
- Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.,Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Kyung Su Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Jin Ho Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Jae-Sung Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Tae Hyun Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Dae Yong Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea
| | - Tae Ryool Koo
- Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Ah Ram Chang
- Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
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Kim KS, Kim K, Chie EK, Kim YJ, Yoon JH, Lee HS, Ha SW. Post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma. Radiat Oncol J 2015; 33:36-41. [PMID: 25874176 PMCID: PMC4394067 DOI: 10.3857/roj.2015.33.1.36] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 03/05/2015] [Accepted: 03/13/2015] [Indexed: 01/07/2023] Open
Abstract
Purpose To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Materials and Methods Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Results Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. Conclusion WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.
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Affiliation(s)
- Kyung Su Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea
| | - Yoon Jun Kim
- Departrment of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Hwan Yoon
- Departrment of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Suk Lee
- Departrment of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sung W Ha
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea. ; Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea
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22
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Park ES, Kwon DH, Park JB, Lee DH, Cho YH, Kim JH, Kim CJ. Gamma Knife surgery for treating brain metastases arising from hepatocellular carcinomas. J Neurosurg 2015; 121 Suppl:102-9. [PMID: 25434943 DOI: 10.3171/2014.7.gks141507] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECT Brain metastases from hepatocellular carcinoma (HCC) are rare, and the evidence of the effectiveness of Gamma Knife surgery (GKS) in this disease is lacking. The authors report their institutional experience with GKS in patients with brain metastases from HCCs. METHODS The authors retrospectively reviewed the medical records of 73 consecutive patients who had a combined total of 141 brain metastases arising from HCCs and were treated with GKS. Sixty-four (87.7%) patients were male, and the mean age of the patients was 52.5 years (range 30-79 years). The mean tumor volume was 7.35 cm(3) (range 0.19-33.7 cm(3)). The median margin dose prescribed was 23 Gy (range 15-32 Gy). Univariate and multivariate survival analyses were performed to identify possible prognostic factors of outcomes. RESULTS The estimated rate of local tumor control was 79.6% at 3 months after GKS. The median overall survival time after GKS was 16 weeks. The actuarial survival rates were 76.7%, 58.9%, and 26.0% at 4, 12, and 24 weeks after GKS, respectively. In the univariate analysis, an age of ≤ 65 years, Child-Pugh Class A (pertaining to liver function), high Karnofsky Performance Scale score (≥ 70), and low Radiation Therapy Oncology Group recursive partitioning analysis class (I or II) were positively associated with the survival times of patients. No statistically significant variable was identified in the multivariate analysis. CONCLUSIONS Although survival was extremely poor in patients with brain metastases from HCCs, GKS showed acceptable local tumor control at 3 months after the treatment. The authors suggest that GKS represents a noninvasive approach that may provide a valuable option for treating patients with brain metastases from HCCs.
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Affiliation(s)
- Eun Suk Park
- Department of Neurosurgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan; and
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23
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Kalogeridi MA, Zygogianni A, Kyrgias G, Kouvaris J, Chatziioannou S, Kelekis N, Kouloulias V. Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review. World J Hepatol 2015; 7:101-112. [PMID: 25625001 PMCID: PMC4295187 DOI: 10.4254/wjh.v7.i1.101] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 10/26/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.
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24
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Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma. J Neurooncol 2014; 120:199-207. [PMID: 25062667 DOI: 10.1007/s11060-014-1546-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 07/05/2014] [Indexed: 10/25/2022]
Abstract
Stratifying patients with brain metastasis (BM) from hepatocellular carcinoma (HCC) by prognostic factors can be useful when making treatment decisions. Nevertheless, a diagnosis-specific graded prognostic assessment (GPA) for HCC has not been well established. We retrospectively reviewed the data from 118 HCC patients newly diagnosed with BM at the Yonsei University Health System between 1985 and 2011. After univariate and multivariate analyses of prognostic factors, those shown to significantly affect survival were used to develop a HCC-specific GPA (HCC-GPA) index. The median overall survival after BM in all patients was 6.1 weeks (95% confidence interval 4.8-7.4 weeks). Using the prognostic factors identified via multivariate analysis, we developed a HCC-GPA index, including number of brain metastases (single: 0.5, multiple: 0 points), alpha-feto protein (<400 ng/mL: 0.5, ≥400 ng/mL: 0 points), and Child-Pugh-Score (A: 3, B: 2, C: 0 points). There were no survival differences for age, sex, performance status, and time interval from initial diagnosis to development of BM. Median survival times from BM were discriminable when applying the HCC-GPA scoring system: 1.7, 3.2, 7.9, and 27.0 weeks for HCC-GPA scores of 0-1.0 (N = 16), 1.5-2.5 (N = 32), 3.0-3.5 (N = 49), and 4.0 (N = 21), respectively (P < 0.001). Although the prognoses of patients with BM from HCC are dismal, the newly developed HCC-GPA index can be used to discriminate the expected prognoses thereof. Moreover, the index may hold value as a tool for selecting patients who may be good candidates for active local treatment.
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Prognostic stratification of brain metastases from hepatocellular carcinoma. J Neurooncol 2014; 120:209-14. [PMID: 25052350 DOI: 10.1007/s11060-014-1547-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 07/06/2014] [Indexed: 01/07/2023]
Abstract
The aim of this study is to evaluate prognostic factors of brain metastases from hepatocellular carcinoma. Medical records of 95 patients who have been diagnosed of brain metastases from hepatocellular carcinoma between January 2000 and December 2011 were retrospectively reviewed. The median age at diagnosis of brain metastases is 56.1 years. Eighty-two patients were male. Median interval from diagnosis of hepatocellular carcinoma to brain metastases was 29.5 months. Eighty-eight patents had extracranial metastases, and the lung was the most frequent involved organ. Motor weakness was the most frequent presenting symptom (49.5%). Intracranial hemorrhage was present in 71 patients (74.7%). Brain metastases were treated with whole brain radiation therapy (WBRT) alone in 57 patients, radiosurgery alone in 18, surgery and WBRT in 6, surgery and radiosurgery in 3, surgery alone in 3, radiosurgery and WBRT in 2, and conservative management only in 6. Median overall survival was 3.0 months. Multivariate analysis showed ECOG performance status, Child-Pugh class, AFP level, number of brain lesions, and treatment modality were associated with survival (p < 0.05). When patients were stratified with four prognostic factors including ECOG performance status, Child-Pugh class, AFP level, and number of brain lesions, median survival time for patients with 0-1, 2, 3-4 risk factors were 5.8 months, 2.5 months and 0.6 months, respectively (p < 0.001). In conclusion, we can estimate the survival of patients by prognostic stratification, although overall prognosis of patients with brain metastases from hepatocellular carcinoma is poor.
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Esmaeilzadeh M, Majlesara A, Faridar A, Hafezi M, Hong B, Esmaeilnia-Shirvani H, Neyazi B, Mehrabi A, Nakamura M. Brain metastasis from gastrointestinal cancers: a systematic review. Int J Clin Pract 2014; 68:890-9. [PMID: 24666726 DOI: 10.1111/ijcp.12395] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Brain metastases (BM) from the gastrointestinal tract (GIT) cancers are relatively rare. Despite those advances in diagnostic and treatment options, life expectancy and quality of life in these patients are still poor. In this review, we present an overview of the studies which have been previously performed as well as a comprehensive strategy for the assessment and treatment of BM from the GIT cancers. METHOD To obtain information on brain metastases from GIT, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included patient characteristics, primary tumor data and brain metastases data. RESULT In our search of the literature, we found 74 studies between 1980 and 2011, which included 2538 patients with brain metastases originated from gastrointestinal cancer. Analysis of available data showed that among 2538 patients who had brain metastases from GIT, a total of 116 patients (4.57%) had esophageal cancer, 148 patients (5.83%) had gastric cancer, 233 patients (9.18%) had liver cancer, 13 patients had pancreas cancer (0.52%) and 2028 patients (79.90%) had colorectal cancer. The total median age of the patients was 58.9 years. CONCLUSION Brain metastases have been considered the most common structural neurological complication of systemic cancer. Due to poor prognosis they influence the survival rate as well as the quality of life of the patients. The treatment of cerebral metastasis depends on the patients' situation and the decisions of the treating physicians. The early awareness of a probable metastasis from GI to the brain will have a great influence on treatment outcomes as well as the survival rate and the quality-of-life of the patients.
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Affiliation(s)
- M Esmaeilzadeh
- Department of Neurosurgery, Hannover Medical School, Hannover, Germany
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Pan Z, Yang G, Yuan T, Pang X, Wang Y, Qu L, Dong L. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report. BMC Cancer 2014; 14:399. [PMID: 24893802 PMCID: PMC4048255 DOI: 10.1186/1471-2407-14-399] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Accepted: 05/29/2014] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. CASE PRESENTATION We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. CONCLUSION To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective.
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Affiliation(s)
- Zhenyu Pan
- Department of Radiotherapy, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Guozi Yang
- Department of Radiotherapy, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Tingting Yuan
- Department of Radiology, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Xiaochuan Pang
- Department of Clinical Laboratory, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Yongxiang Wang
- Department of Clinical Laboratory, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Limei Qu
- Department of Pathology, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
| | - Lihua Dong
- Department of Radiotherapy, Norman Bethune First Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China
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Chen H, Li J, Wang L, Cong N, Shi C, Song J, Bu W. Hepatocellular carcinoma metastasis to the lacrimal gland: A case report. Oncol Lett 2014; 8:911-913. [PMID: 25013516 PMCID: PMC4081277 DOI: 10.3892/ol.2014.2191] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Accepted: 05/07/2014] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a globally common neoplasm, with regional metastasis associated with >50% of the tumors. Extrahepatic metastasis is also common, with the lungs, diaphragm, abdominal lymph nodes and bone being the most frequently affected regions. However, to the best of our knowledge, HCC metastasis to the lacrimal gland has not been reported in the literature. Only one case of metastasis to the lacrimal sac from a renal cell carcinoma has been reported. The current study presents the case of a 56-year-old male with ocular symptoms who was eventually diagnosed with HCC. The therapeutic alternatives for such cases are also discussed according to the reviewed literature. Clinicians should be watchful for the appearance of tumors in the lacrimal gland in patients with a history of malignancy.
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Affiliation(s)
- Hua Chen
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Jinpeng Li
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Lijun Wang
- Department of Computerized Tomography, Shandong Medical Imaging Research Institute, Jinan, Shandong 250000, P.R. China
| | - Ning Cong
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Congcong Shi
- Six Ward of Shandong Mental Health Center, Jinan, Shandong 250014, P.R. China
| | - Jinlong Song
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Wenzhe Bu
- Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
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Xu Q, Wu P, Feng Y, Ye K, Tong Y, Zhou Y. Gamma knife surgery for brain metastasis from hepatocellular carcinoma. PLoS One 2014; 9:e88317. [PMID: 24516635 PMCID: PMC3917852 DOI: 10.1371/journal.pone.0088317] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 01/06/2014] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVES The authors evaluated the results of Gamma knife surgery (GKS) for the treatment of metastatic brain tumors from hepatocellular carcinoma (HCC). METHODS AND RESULTS The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 14 patients with metastatic brain tumors from HCC who underwent GKS. Twelve (85.7%) patients were male. The mean age of the patients was 53±12 years. There were totally 22 brain metastases in 14 patients and 8 patients (57.1%) presented with a single brain lesion. Intracranial hemorrhages occurred in 13 (59.1%) of the 22 lesions. The mean KPS score was 81±14 (range 50-100). Eleven (78.6%) patients were classified as RTOG RPA Class 2. The mean tumor volume was 8.16±8.15 cm(3) (range 0.59-27.0 cm(3)). The mean marginal dose prescribed was 18.7±3.2 Gy (range 10.0-22.0 Gy). The mean number of shots administered was 10±9 (range 1-27). The median overall survival time after GKS was 5.0±0.93 months (95% CI 3.2-6.8). No complications related to the radiosurgical treatment were identified. Multivariate analysis showed that the total volume of brain metastases, the RTOG RPA class and serum AFP level were significantly correlated with patients' survival time. CONCLUSIONS Although survival was extremely poor in patients with brain metastasis (BM) from HCC, GKS was shown to lead to prolongation of the survival time. Accordingly, GKS can be considered as a valuable treatment option for proper patients with HCC BM.
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Affiliation(s)
- Qingsheng Xu
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
- * E-mail:
| | - Pan Wu
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Yiping Feng
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Ke Ye
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Ying Tong
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
| | - Yongqing Zhou
- Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P. R. China
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Han MS, Moon KS, Lee KH, Cho SB, Lim SH, Jang WY, Jung TY, Kim IY, Jung S. Brain metastasis from hepatocellular carcinoma: the role of surgery as a prognostic factor. BMC Cancer 2013; 13:567. [PMID: 24289477 PMCID: PMC3879022 DOI: 10.1186/1471-2407-13-567] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 11/27/2013] [Indexed: 02/06/2023] Open
Abstract
Background The incidence of brain metastasis from hepatocellular carcinoma (HCC) is expected to increase as a result of prolonged survival due to the recent advances in HCC treatment. However, there is no definite treatment strategy for brain metastasis from HCC mainly due to its rarity and dismal prognosis. To provide helpful recommendations in treatment of brain metastasis from HCC, the authors aimed to identify prognostic factors that influence survival rates with a review of the recently published data. Methods Thirty-three cases of brain metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC patients and reviewed retrospectively in terms of clinical and radiological features. Results Median overall survival time after diagnosis of brain metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-, 6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival of the patients treated with surgical resection or surgical resection followed by whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p < 0.001). Child-Pugh’s classification A group had a longer median survival time than Child-Pugh’s classification B or C group (14.4 weeks vs 8.4 weeks, p = 0.038). RPA class I & II group had also a longer median survival time than RPA class III group did (13.4 weeks vs 2.4 weeks, p = 0.001). Surgical resection (hazard ratio [HR] 0.23, 95% CI 0.08-0.66, p = 0.006) and good liver function at the time of brain metastasis (HR 0.25, 95% CI 0.09-0.69, p = 0.007) were found to be the powerful prognostic factors for favorable survival in the multivariate analysis. In addition, presence of intratumoral hemorrhage was a statistically significant prognostic factor for survival. Conclusion Although HCC patients with brain metastasis showed a very dismal prognosis, surgical intervention was shown to lead to relative prolongation of the survival time, especially in those with preserved hepatic function.
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Affiliation(s)
| | - Kyung-Sub Moon
- Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital & Medical School, Gwangju, South Korea.
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Abstract
A 59-year-old male with hepatocellular carcinoma (HCC) due to liver cirrhosis caused by the hepatitis C virus underwent cadaveric whole liver transplantation. Two years later, he had a metastatic HCC in the superior mediastinum. Over the following postoperative year, he underwent transcatheter arterial chemoembolization (TACE) for 4 tumors in the implanted liver. In the third post-TACE month, he was emergently hospitalized due to intracerebral hematoma with a tumor invading the bone in the medial frontal segment. He underwent emergency intracranial tumorectomy and hemorrhage removal. The histopathologic diagnosis was metastatic HCC. He regained consciousness as well as the ability to speak and to feed himself, resulting in an improved quality of life. The incidence of HCC recurrence after liver transplantation is observed in approximately 8% to 11% of selected cases, with frequent relapses observed in the implanted liver, bones, adrenal glands, and lungs. Mediastinal and intracranial metastases from HCC post-liver transplantation are very rare.
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Park TY, Na YC, Lee WH, Kim JH, Chang WS, Jung HH, Chang JH, Chang JW, Park YG. Treatment Options of Metastatic Brain Tumors from Hepatocellular Carcinoma: Surgical Resection vs. Gamma Knife Radiosurgery vs. Whole Brain Radiation Therapy. Brain Tumor Res Treat 2013; 1:78-84. [PMID: 24904896 PMCID: PMC4027101 DOI: 10.14791/btrt.2013.1.2.78] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 09/09/2013] [Accepted: 09/27/2013] [Indexed: 12/30/2022] Open
Abstract
Objective Although metastasis of hepatocellular carcinoma to the brain is uncommon, it is associated with a very high mortality rate and most patients usually expire within 1 year after brain metastasis. The aim of this study is to identify the effectiveness of the active interventions such as gamma knife radiosurgery or surgical intervention for these patients. Methods We retrospectively reviewed the medical records and imaging data of 59 patients with metastatic brain tumors from hepatocellular carcinoma from May 2004 to September 2012. The study included patients with available clinical and radiological data who had been diagnosed with metastatic hepatocellular carcinoma of the brain, confirmed by magnetic resonance imaging. The overall survival time was analyzed and compared according to each risk factor. Results The mean age at diagnosis of metastatic brain tumor was 52.2 years (14-77). The mean follow-up duration was 13.3 weeks (0.1-117.6). Overall median survival was 4.3 weeks (95% confidence interval, 2.2-6.4). The results from an analysis of clinical factors related to survival revealed that treatment modalities were significantly related to the patient's survival (log rank, p=0.006). Twenty patients (32.8%) experienced tumor bleeding, and the survival time of the patients with tumor bleeding tended to be shorter, although the result was not statistically significant (log rank, p=0.058). Hepatic reserve, by Child-Pugh classification, was grade A in 38 patients (64.4%), grade B in 16 patients (27.1%), and grade C in 5 patients (8.5%), and was significantly related to the patient's survival (log rank, p=0.000). Conclusion Although patients with metastatic brain tumors from hepatocellular carcinoma showed poor survival, active intervention including surgical resection or gamma knife radiosurgery may result in better survival, especially if patients have preserved liver function.
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Affiliation(s)
- Tae Yong Park
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Young Chul Na
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Won Hee Lee
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Hee Kim
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Won Seok Chang
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Ho Jung
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Hee Chang
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Woo Chang
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
| | - Young Gou Park
- Department of Neurosurgery, Yonsei Gamma Knife Center, Yonsei University College of Medicine, Seoul, Korea
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Chen CC, Yeh HZ, Chang CS, Ko CW, Lien HC, Wu CY, Hung SW. Transarterial embolization of metastatic mediastinal hepatocellular carcinoma. World J Gastroenterol 2013; 19:3512-3516. [PMID: 23801848 PMCID: PMC3683694 DOI: 10.3748/wjg.v19.i22.3512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Revised: 03/05/2013] [Accepted: 04/19/2013] [Indexed: 02/06/2023] Open
Abstract
This paper introduces an innovative treatment for extra-hepatic metastasis of hepatocellular carcinoma. A 71-year-old patient had a stable liver condition following treatment for hepatocellular carcinoma, but later developed symptomatic mediastinal metastasis. This rapidly growing mediastinal mass induced symptoms including cough and hoarseness. Serial sessions of transarterial embolization (TAE) successfully controlled this mediastinal mass with limited side effects. The patient’s survival time since the initial diagnosis of the mediastinal hepatocellular carcinoma was 32 mo, significantly longer than the 12 mo mean survival period of patients with similar diagnoses: metastatic hepatocellular carcinoma and a liver condition with a Child-Pugh class A score. Currently, oral sorafenib is the treatment of choice for metastatic hepatocellular carcinoma. Recent studies indicate that locoregional treatment of extra-hepatic metastasis of hepatocellular carcinomas might also significantly improve the prognosis in patients with their primary hepatic lesions under control. Many effective locoregional therapies for extrahepatic metastasis, including radiation and surgical resection, may provide palliative effects for hepatocellular carcinoma-associated mediastinal metastasis. This case report demonstrates that TAE of metastatic mediastinal hepatocellular carcinoma provided this patient with tumor control and increased survival time. This finding is important as it can potentially provide an alternative treatment option for patients with similar symptoms and diagnoses.
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Okimoto K, Ogasawara S, Chiba T, Kanai F, Yokota H, Motoyama T, Suzuki E, Ooka Y, Tawada A, Iwadate Y, Saeki N, Yokosuka O. Successful resection of intracranial metastasis of hepatocellular carcinoma. Case Rep Gastroenterol 2013; 7:182-7. [PMID: 23626520 PMCID: PMC3635693 DOI: 10.1159/000350673] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Intracranial metastasis of hepatocellular carcinoma (HCC) is rare, but has an extremely poor prognosis. We report a case with successful surgical removal of intracranial metastasis of HCC. A 32-year-old man was admitted to our hospital with severe vomiting. He had been followed for liver cirrhosis due to hepatitis B virus infection and received a right hepatic trisectionectomy for HCC 1 year earlier. For the recurrence of HCC, sorafenib had been administered 6 months before admission. On admission, he exhibited consciousness disturbance, which gradually worsened. Two days later, both computed tomography and magnetic resonance imaging revealed an intra-axial tumor with perifocal edema and hemorrhage in the left frontal lobe. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of moderately differentiated HCC cells. The day after surgical resection of the tumor, his consciousness returned to normal. Subsequently, he was treated with hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin using an implanted port-catheter system. Surgical resection of intracranial metastasis of HCC would be important and meaningful in some cases.
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Affiliation(s)
- Kenichiro Okimoto
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Menis J, Fontanella C, Follador A, Fasola G, Aprile G. Brain metastases from gastrointestinal tumours: Tailoring the approach to maximize the outcome. Crit Rev Oncol Hematol 2013; 85:32-44. [DOI: 10.1016/j.critrevonc.2012.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Revised: 03/30/2012] [Accepted: 04/11/2012] [Indexed: 12/18/2022] Open
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Abstract
Intracranial hemorrhage (ICH) is a common neurological emergency in patients with cancer, typically occurring late in the disease course, although it occasionally heralds the cancer diagnosis. ICH in these patients often occurs from unique mechanisms, especially intratumoral hemorrhage or coagulopathy, whereas hypertensive hemorrhage is rare. Lung, melanoma, breast, and glioblastoma multiforme are the most commonly associated solid tumors, partly because of their ubiquity and frequent brain involvement, whereas leukemia is the most commonly associated hematological cancer. Patients typically present with focal neurological deficits, headache, and encephalopathy, and their initial diagnostic evaluation and management should follow standard guidelines, although steroids and/or surgical resection should be strongly considered in those with intratumoral hemorrhage. Short-term outcomes are comparable to ICH in the community, whereas long-term outcomes are generally poor, corresponding to the prognosis of the underlying cancer. This review focuses on the recent advances and special considerations in cancer-related intracranial hemorrhage.
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Brain metastases from hepatocellular carcinoma in two Caucasian Australian patients. J Clin Neurosci 2012; 19:1442-5. [PMID: 22898198 DOI: 10.1016/j.jocn.2012.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Accepted: 02/24/2012] [Indexed: 11/23/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the world's most common malignant cancers. Its incidence is particularly high in Asia and sub-Saharan Africa but, in recent years, significant increases in HCC have been observed in Australia and other Western countries. Therapeutic advances have contributed to improved survival rates in patients with HCC although intracranial metastases are extremely rare. Here we report the first two published Australian cases of brain metastases from HCC, both in Caucasian patients.
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Jung SM, Jang JW, You CR, Yoo SH, Kwon JH, Bae SH, Choi JY, Yoon SK, Chung KW, Kay CS, Jung HS. Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 2012; 27:684-689. [PMID: 21916984 DOI: 10.1111/j.1440-1746.2011.06917.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM There has been little information about the long-term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC. METHODS Between 2004 and 2009, a total of 240 consecutive patients with HCC and extrahepatic metastasis were recruited. Based on tumor extent, performance, and hepatic function, the patients underwent locoregional and/or systemic treatments. The treatment response of the intrahepatic tumor after extrahepatic metastasis and other prognostic parameters were analyzed retrospectively. RESULTS During the mean follow up of 276 days, 222 patients died; the median survival time was 146 days. Multivariate analysis revealed that Child-Pugh class A, smaller hepatic tumor size, absence of portal venous invasion, single metastatic organ involvement, and objective treatment response of the intrahepatic tumor were the favorable prognostic factors for survival. Of the 183 evaluable patients, 24 achieved complete or partial response for intrahepatic tumors after treatment. The overall survival for the 24 responders was significantly improved, with a median of 521 days, as compared to 170 days for the remaining 159 patients without objective tumor response. The leading cause of death was progressive intrahepatic tumor. CONCLUSIONS Intrahepatic tumor status and hepatic reserve are among the significant predictors of survival in patients with HCC and extrahepatic metastases. This study indicates that even in patients with metastases from advanced HCC, therapeutic approaches to control intrahepatic tumors are important in improving patient survival.
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Affiliation(s)
- Seung Min Jung
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, Korea
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Jiang XB, Ke C, Zhang GH, Zhang XH, Sai K, Chen ZP, Mou YG. Brain metastases from hepatocellular carcinoma: clinical features and prognostic factors. BMC Cancer 2012; 12:49. [PMID: 22292912 PMCID: PMC3297522 DOI: 10.1186/1471-2407-12-49] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Accepted: 02/01/2012] [Indexed: 12/28/2022] Open
Abstract
Background Brain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC. Methods Between January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Results Forty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival. Conclusions BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.
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Affiliation(s)
- Xiao-Bing Jiang
- State Key Laboratory of Oncology in South China and Department of Neurosurgery, Sun Yat-sen University Cancer Center, No, 651, Dong Feng Road East, Guangzhou 510060, People's Republic of China
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Zhang H, Cai H, Lu X, Muzik O, Peng F. Positron emission tomography of human hepatocellular carcinoma xenografts in mice using copper (II)-64 chloride as a tracer with copper (II)-64 chloride. Acad Radiol 2011; 18:1561-1568. [PMID: 22055798 PMCID: PMC3921175 DOI: 10.1016/j.acra.2011.08.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2011] [Revised: 08/13/2011] [Accepted: 08/16/2011] [Indexed: 11/25/2022]
Abstract
RATIONALE AND OBJECTIVES The aim of this study was to assess copper metabolism of human hepatocellular carcinoma (HCC) with positron emission tomographic (PET) imaging using copper (II)-64 chloride ((64)CuCl(2)) as a tracer. MATERIALS AND METHODS PET imaging of athymic mice (n = 5) bearing extrahepatic HCC xenografts was performed 24 hours after the intravenous injection of (64)CuCl(2), followed by ex vivo tissue radioactivity assay. Expression of human copper transporter 1 (hCTR1) in HCC cells and tissues was examined by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. RESULTS The extrahepatic HCC xenografts in mice with increased uptake of (64)Cu radionuclide were visualized on the micro-PET images obtained 24 hours after the intravenous injection of (64)CuCl(2). PET quantitative analysis revealed increased (64)Cu radioactivity in tumor tissues (2.7 ± 0.6 %ID/g) compared to that in the soft tissue of the left shoulder opposite to the tumor site (0.6 ± 0.2 %ID/g) and the brain (0.7 ± 0.1 %ID/g) but lower than that of the liver (16.6 ± 1.3 %ID/g). Expression of hCTR1 in the HCC cells and xenograft tumor tissues was demonstrated by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. The expression level of hCTR1 in the Hep3B HCC xenograft tissues was lower than that detected in the normal hepatic tissues and the tissue samples of well-differentiated primary HCC. Variable expression of hCTR1 was detected in the tissue samples of moderately differentiated primary HCC. CONCLUSIONS Extrahepatic human HCC xenografts in mice could be localized with (64)CuCl(2) PET imaging, which might be useful for the localization and quantitative assessment of copper metabolism in extrahepatic metastases of HCC in humans.
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Affiliation(s)
- Haiyuan Zhang
- Carman & Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
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Abstract
Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has recently been paradoxically increasing due to increased survival with effective locoregional therapies. The intrahepatic stage of the tumor is important for determining the risk of an extrahepatic lesion. Almost all patients with intrahepatic stage T(3-4), with or without EHM, die of progressive intrahepatic HCC but not due to EHM; thus, the majority of patients with HCC and EHM need to undergo concurrent treatment for intrahepatic HCC. There is no convincing evidence, to date, that systemic chemotherapy improves overall survival. Sorafenib is the first systemic agent that has demonstrated a significant survival benefit in patients with advanced HCC; however, the modest improvement of 3 months is far from satisfactory. Therefore, most hepatologists still rely on the conventional multidisciplinary approach to treat patients with EHM. The concept of the multidisciplinary treatment is the combination of locoregional therapies for both the intrahepatic HCC and symptomatic EHM when confined to a single organ. Targeted therapy may be considered for patients with advanced intrahepatic HCC and multiple EHM, however the potential efficacy of this approach requires confirmation. The outcome of ongoing clinical trials of the multidisciplinary approach, combining conventional locoregional therapy and targeted systemic therapy, is pending.
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Affiliation(s)
- Hyo-Suk Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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Modern management of rare brain metastases in adults. J Neurooncol 2011; 105:9-25. [DOI: 10.1007/s11060-011-0613-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2010] [Accepted: 05/22/2011] [Indexed: 12/13/2022]
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Uchino K, Tateishi R, Shiina S, Kanda M, Masuzaki R, Kondo Y, Goto T, Omata M, Yoshida H, Koike K. Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer 2011; 117:4475-83. [PMID: 21437884 DOI: 10.1002/cncr.25960] [Citation(s) in RCA: 320] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2010] [Revised: 12/27/2010] [Accepted: 01/03/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease. METHODS In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow-up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split-sample method with a testing set and a training set. RESULTS The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03-108.7 months). In univariate analysis of the training set (n = 171), performance status, Child-Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α-fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73. CONCLUSIONS The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis.
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Affiliation(s)
- Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Zhou H, Lv L, Ding X. Primary clear cell carcinoma of the liver with intracerebral hemorrhage as first presentation: case report. ONKOLOGIE 2011; 34:51-3. [PMID: 21346386 DOI: 10.1159/000323383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Haiyang Zhou
- Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
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Hsiao SY, Chen SF, Chang CC, Lin CH, Chang WN, Lu CH, Chuang YC, Tsai NW. Central nervous system involvement in hepatocellular carcinoma: clinical characteristics and comparison of intracranial and spinal metastatic groups. J Clin Neurosci 2011; 18:364-8. [PMID: 21247770 DOI: 10.1016/j.jocn.2010.04.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2010] [Revised: 03/28/2010] [Accepted: 04/04/2010] [Indexed: 01/12/2023]
Abstract
From January 1993 to December 2006 we analyzed the clinical characteristics of patients with hepatocellular carcinoma (HCC) with central nervous system (CNS) metastasis at the Kaohsiung Chang Gung Memorial Hospital, Taiwan. Forty-six patients with HCC and CNS metastasis were identified, of whom 36 had intracranial metastasis and 10 had spinal metastasis. The clinical presentations, laboratory data and imaging studies were collected and analyzed. The age at the time of HCC diagnosis ranged from 34 to 78 years; CNS metastasis occurred between 0 and 85 months after diagnosis and death followed between 0 and 93 months later. The Glasgow Coma Scale (GCS) score at the time of CNS metastasis ranged from 7 to 15 and the Child-Pugh score at diagnosis of HCC ranged from 5 to 15. Patients with spinal metastasis had a higher GCS score and lower Child-Pugh score at diagnosis. None of the serum biochemical studies showed unique abnormalities. From the data currently available, intracranial metastasis is the most common site of CNS metastasis of HCC. Advances in treating and diagnosing HCC have improved patient outcomes remarkably; however, CNS metastasis continues to have a grave prognosis. Without a specific biomarker for predicting CNS involvement in HCC, a high index of suspicion for the diagnosis should be maintained, particularly in HCC hyperendemic areas such as Taiwan.
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Affiliation(s)
- Sheng-Yuan Hsiao
- Department of Family Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Shao YY, Lu LC, Cheng AL, Hsu CH. Increasing incidence of brain metastasis in patients with advanced hepatocellular carcinoma in the era of antiangiogenic targeted therapy. Oncologist 2011; 16:82-6. [PMID: 21212425 DOI: 10.1634/theoncologist.2010-0272] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
AIM Brain metastasis was regarded, until recently, as a rare and late-stage event in patients with hepatocellular carcinoma (HCC). With the prolongation of survival in patients with advanced HCC by molecular targeted agents, this may have changed. We aimed to examine whether or not the incidence of brain metastasis in these patients has increased. METHODS Between June 2005 and May 2009, 158 advanced HCC patients in total with either metastatic or locally advanced disease untreatable by locoregional therapies were enrolled in clinical trials of first-line antiangiogenic therapies. The clinicopathologic features and survival times of those who developed brain metastasis were analyzed. RESULTS Eleven (7%) of 158 advanced HCC patients, with a median follow-up of 26.6 months, were diagnosed with brain metastasis as a result of compatible symptoms, confirmed by brain imaging. All 11 patients had extrahepatic metastasis upon enrollment, and 10 of them had lung metastasis. The median time to brain metastasis was 9.6 months (range, 0.6-19.6 months). The median overall survival (OS) time after diagnosis of brain metastasis was 4.6 months (range, 0.7-12.6 months). Four patients received brain tumor excision, and their survival duration after brain metastasis tended to be longer than that of those who did not (median OS time, 6.1 months versus 3.1 months). CONCLUSIONS In the era of antiangiogenic targeted therapy, the importance of brain metastasis for advanced HCC patients may have increased.
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Affiliation(s)
- Yu-Yun Shao
- Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan
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Fujihara H, Chikazu D, Saijo H, Suenaga H, Mori Y, Iino M, Hamada Y, Takato T. Metastasis of hepatocellular carcinoma into the mandible with radiographic findings mimicking a radicular cyst: a case report. J Endod 2010; 36:1593-6. [PMID: 20728734 DOI: 10.1016/j.joen.2010.05.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2010] [Revised: 05/07/2010] [Accepted: 05/19/2010] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a common neoplasm worldwide, with more than half of the tumors associated with regional metastasis. Extrahepatic metastasis is also common, and the most frequently affected sites are the lungs, abdominal lymph nodes, diaphragm, and bone. However, HCC metastasis to the mandible is rare, with approximately 50 cases reported in the literature. METHODS In this report, we describe a case of HCC metastasis to the mandible at the apex of #18 root in a 62-year-old man. This patient had already been diagnosed with metastasis to pancreatic caput lymph node. The radiographic features of the mandible resembled radicular cyst and did not show typical findings of malignancy. RESULTS Under the first diagnosis of radicular cyst, root canal treatment was initially performed, and then surgical treatment of the removal of the cystic lesion and #18 extraction were performed. Finally, the lesion was diagnosed as HCC metastasis from pathological examination. Consequently, he received constitutional chemotherapy in the hepatitis unit and is now in remission. CONCLUSION This case shows the importance of considering the differential diagnosis of malignancy.
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Affiliation(s)
- Hisako Fujihara
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, Yokohama, Kanagawa, Japan.
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Woo KM, Kim BC, Cho KT, Kim EJ. Spontaneous epidural hematoma from skull base metastasis of hepatocellular carcinoma. J Korean Neurosurg Soc 2010; 47:461-3. [PMID: 20617094 DOI: 10.3340/jkns.2010.47.6.461] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2009] [Revised: 12/04/2009] [Accepted: 05/17/2010] [Indexed: 01/30/2023] Open
Abstract
We report a case of an acute spontaneous epidural hematoma (EDH) due to skull base metastasis in a 46-year-old male patient with hepatocellular carcinoma (HCC). The patient presented with the acute onset of severe headache followed by unconsciousness, and computed tomography showed a large EDH in the right temporal and parietal lobes with midline shift. Emergency evacuation of the EDH was performed, and the hemorrhage was determined to be secondary to skull base metastasis of HCC.
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Affiliation(s)
- Kwang Moo Woo
- Department of Neurosurgery, Dongguk University College of Medicine, Dongguk University International Hospital, Goyang, Korea
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Han JH, Kim DG, Park JC, Chung HT, Paek SH, Chung YS. Little response of cerebral metastasis from hepatocellular carcinoma to any treatments. J Korean Neurosurg Soc 2010; 47:325-31. [PMID: 20539790 DOI: 10.3340/jkns.2010.47.5.325] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2010] [Revised: 04/15/2010] [Accepted: 05/10/2010] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE We retrospectively evaluated the survival outcome of patients with brain metastasis from hepatocellular carcinoma (HCC). METHODS Between 1991 and 2007, a total of 20 patients were diagnosed as having brain metastasis from HCC. The mean age of the patients was 55 +/- 13 years, and 17 (85.0%) were men. Seventeen (85.0%) patients had already extracranial metastases. The median time from diagnosis of HCC to brain metastasis was 18.5 months. Fourteen (70.0%) patients had stroke-like presentation due to intracerebral hemorrhage (ICH). Ten (50.0%) patients had single or solitary brain metastasis. Among a total of 34 brain lesions, 31 (91.2%) lesions had the hemorrhagic components. RESULTS The median survival time was 8 weeks (95% CI, 5.08-10.92), and the actuarial survival rates were 85.0%, 45.0%, 22.5%, and 8.4% at 4, 12, 24, and 54 weeks. Age < 60 years, treatment of the primary and/or extracranial lesions, and recurrent ICH were the possible prognostic factors (p = 0.044, p < 0.001, and p = 0.111, respectively). The median progression-free survival (PFS) time was 3 months (95% CI, 0.95-5.05). CONCLUSION The overall survival of the patients with brain metastasis from HCC was very poor with median survival time being only 8 weeks. However, the younger patients less than 60 years and/or no extracranial metastases seem to be a positive prognostic factor.
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Affiliation(s)
- Jung Ho Han
- Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Korea
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Besse B, Lasserre SF, Compton P, Huang J, Augustus S, Rohr UP. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 2009; 16:269-78. [PMID: 20028762 DOI: 10.1158/1078-0432.ccr-09-2439] [Citation(s) in RCA: 170] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Patients with central nervous system (CNS) metastases were excluded from bevacizumab trials following a case of fatal cerebral hemorrhage in a patient with hepatocellular carcinoma in 1997. Safety information for bevacizumab-treated patients with CNS metastases was reviewed to determine whether general exclusion of these patients from bevacizumab treatment is still justified. EXPERIMENTAL DESIGN A retrospective exploratory analysis was conducted using datasets from 13 randomized controlled phase II/III trials (dataset A), two open-label single-arm safety trials (dataset B), and two prospective studies including patients with treated CNS metastases (dataset C). In datasets A and B, known CNS metastasis was an exclusion criterion; patients with CNS metastasis had unrecognized CNS metastases at study entry or developed them during the trial. All reported cerebral hemorrhage grades in patients with CNS metastases were quantified. RESULTS In dataset A, occult brain metastases were identified in 187 of 8,443 patients (91 in bevacizumab arms and 96 in non-bevacizumab arms). Three bevacizumab-treated patients (3.3%) developed grade 4 cerebral hemorrhage, whereas one control-arm patient (1.0%) developed grade 5 cerebral hemorrhage. In dataset B, 321 of 4,382 patients had initially occult CNS metastases, in whom two grade 1 and one grade 3 cerebral hemorrhage (0.9%) were reported. In 131 patients with treated CNS metastases in dataset C, one bevacizumab-treated patient (0.8%) developed grade 2 cerebral hemorrhage. CONCLUSIONS In this selected population, patients with CNS metastases are at similar risk of developing cerebral hemorrhage, independent of bevacizumab therapy. Consequently, such patients with CNS metastases from advanced/metastatic breast cancer, non-small cell lung carcinoma, and renal and colorectal cancer should not be generally excluded from bevacizumab therapy or clinical trials.
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