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Brahmbhatt M, Prenner S, Bittermann T. Liver Transplantation for Hepatic Epithelioid Hemangioendothelioma Is Facilitated by Exception Points With Acceptable Long-term Outcomes. Transplantation 2020; 104:1187-1192. [PMID: 31577674 DOI: 10.1097/tp.0000000000002982] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the United States under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the United States for patients with HEHE remains understudied. METHODS This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From February 27, 2002 to January 31, 2018, 131 adults waitlisted for LT with HEHE were identified by free-text entry. RESULTS Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median model for end-stage liver disease score at LT was 7 ((interquartile range [IQR]: 6-11) and waiting time 78.5 days (IQR: 29.5-237.5). Unadjusted post-LT survival of HEHE recipients at 1-, 3-, and 5-years from LT was 88.6%, 78.9%, and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (P = 0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% versus 0.5%). CONCLUSIONS The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT.
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Affiliation(s)
- Mihir Brahmbhatt
- Division of General Internal Medicine, University of Pennsylvania, Philadelphia, PA
| | - Stacey Prenner
- Division of Gastroenterology & Hepatology, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Division of Gastroenterology & Hepatology, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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2
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Abstract
Purpose of Review Liver transplantation is an important therapeutic option for patients with life-limiting liver disease, which may present in the form of acute liver failure, end-stage chronic liver disease, primary hepatic cancers, or inborn metabolic disorders. While significant strides have been made with respect to liver transplantation outcomes, the practice is constrained by an organ supply/demand mismatch. The purpose of this review, therefore, is to review the general indications and contraindication to liver transplantation, and to provide an overview of the transplant evaluation process. These considerations ultimately shape the specific criteria for patient selection, which will continue to evolve as means are developed to expand the donor pool, improve surgical techniques, broaden indications for safe transplant, and extend the lifetime of a graft. Recent Findings Selected patients with unresectable hilar cholangiocarcinoma may be candidates for liver transplantation. Patients over 65 years may be transplant candidates if they possess a favorable comorbidity profile. Patients at body mass index extremes (≥ 40 or < 18.5) have increased post-transplant mortality and require nutritional evaluation. Summary Liver transplantation may be life saving for patients with acute liver failure or end-stage liver disease. It is therefore critical for healthcare providers caring for patients with liver disease to be familiar with the general indications for transplantation and to know when it is appropriate or inappropriate to refer for transplant evaluation.
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Affiliation(s)
- Nadim Mahmud
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA USA
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3
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Telli TA, Okten IN, Tuylu TB, Demircan NC, Arikan R, Alan O, Ercelep O, Ones T, Yildirim AT, Dane F, Yumuk PF. VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature. Curr Probl Cancer 2020; 44:100568. [PMID: 32201052 DOI: 10.1016/j.currproblcancer.2020.100568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 03/02/2020] [Indexed: 12/15/2022]
Abstract
Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor originating from endothelial cells. Clinical aspect of the disease covers a wide spectrum from a low-grade tumor to a fatal cancer. Most common sites of EHE are reported as lung, liver and bone. Hepatic EHE (HEHE) is a clinical form with an incidence of less than 1 person in a million. Due to rarity of the disease, there is no standard therapy established. Surgery and liver transplantation still seem to be the best approach if possible. However, most of the patients present with unresectable or metastatic disease. Many conventional chemotherapeutic agents and antiangiogenic drugs have been reported previously in the literature with inconsistent outcomes. Here we report 4 cases of HEHE, who benefit distinctly from anti-VEGF treatments in different settings. While combination of paclitaxel and bevacizumab resulted in partial response in 3 patients, one of them also achieved long-term disease stabilization with bevacizumab maintenance with no adverse event. Two of the patients had clear benefit from pazopanib during the course of disease. One patient was treated with thalidomide for 18 months with stable disease, and is still being followed without any treatment. Although targeting VEGF-VEGFR pathway seems to be the best approach in HEHE, randomized studies are urgently needed to support these findings.
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Affiliation(s)
- Tugba Akin Telli
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ilker Nihat Okten
- Division of Medical Oncology, Department of Internal Medicine, Medeniyet University School of Medicine, Istanbul, Turkey
| | - Tuğba Basoglu Tuylu
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Nazim Can Demircan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Rukiye Arikan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ozkan Alan
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Ozlem Ercelep
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Tunc Ones
- Department of Nucleer Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | | | - Faysal Dane
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Perran Fulden Yumuk
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
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4
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Caicedo LA, Delgado A, Duque M, Jiménez DF, Sepulveda M, García JA, Thomas LS, Garcia VH, Aristizabal AM, Gomez C, Arrunategui AM, Manzi E, Millan M, Villegas JI, Serrano O, Holguín A, Echeverri GJ. Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma. Transplant Proc 2018; 50:485-492. [PMID: 29579833 DOI: 10.1016/j.transproceed.2017.11.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Accepted: 11/11/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.
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Affiliation(s)
- L A Caicedo
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - A Delgado
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - M Duque
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - D F Jiménez
- Hepatology Department Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - M Sepulveda
- Hepatology Department Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - J A García
- Hepatology Department Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - L S Thomas
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - V H Garcia
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - A M Aristizabal
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - C Gomez
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - A M Arrunategui
- Pathology Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - E Manzi
- Centro de Investigaciones Clínicas, Fundación Valle del Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - M Millan
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - J I Villegas
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - O Serrano
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - A Holguín
- Radiology Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia
| | - G J Echeverri
- Transplant Surgery Department, Fundación Valle de Lilí, Cali, Colombia; Centro para la Investigación en Cirugía Avanzada y Trasplantes, Universidad ICESI, Cali, Colombia.
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5
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Lee HW, Suh KS. Liver transplantation for advanced hepatocellular carcinoma. Clin Mol Hepatol 2016; 22:309-318. [PMID: 27729631 PMCID: PMC5066382 DOI: 10.3350/cmh.2016.0042] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 08/10/2016] [Indexed: 12/12/2022] Open
Abstract
There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future.
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Affiliation(s)
- Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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6
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Han P, Sun D, Yang J. Interaction between periodontitis and liver diseases. Biomed Rep 2016; 5:267-276. [PMID: 27588170 PMCID: PMC4998044 DOI: 10.3892/br.2016.718] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 06/09/2016] [Indexed: 02/07/2023] Open
Abstract
Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue.
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Affiliation(s)
- Pengyu Han
- The Liver Disease Diagnosis and Treatment Center of PLA, Bethune International Peace Hospital, Shijiazhuang, Hebei 050082, P.R. China
| | - Dianxing Sun
- The Liver Disease Diagnosis and Treatment Center of PLA, Bethune International Peace Hospital, Shijiazhuang, Hebei 050082, P.R. China
| | - Jie Yang
- Department of Public Healthcare, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
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7
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Byrne TJ, Rakela J. Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy. World J Transplant 2016; 6:306-313. [PMID: 27358775 PMCID: PMC4919734 DOI: 10.5500/wjt.v6.i2.306] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 02/02/2016] [Accepted: 03/23/2016] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection - even with favorable survival - is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, loco-regional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.
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8
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Simo KA, Halpin LE, McBrier NM, Hessey JA, Baker E, Ross S, Swan RZ, Iannitti DA, Martinie JB. Multimodality treatment of intrahepatic cholangiocarcinoma: A review. J Surg Oncol 2016; 113:62-83. [DOI: 10.1002/jso.24093] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 10/31/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Kerri A. Simo
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Laura E. Halpin
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Nicole M. McBrier
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
| | | | - Erin Baker
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Samuel Ross
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Ryan Z. Swan
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - David A. Iannitti
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - John B. Martinie
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
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9
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Moray G, Kirnap M, Akdur A, Soy E, Tezcaner T, Boyvat F, Ozdemir H, Haberal M. Outcomes of Patients With Hepatocellular Carcinoma After Liver Transplant. EXP CLIN TRANSPLANT 2015; 13 Suppl 3:30-2. [PMID: 26640906 DOI: 10.6002/ect.tdtd2015.o22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Liver transplant is one of the few effective treatments for hepatocellular carcinoma. Our aim in this study was to evaluate the risk factors for hepatocellular carcinoma recurrence after liver transplant. MATERIALS AND METHODS In this retrospective study, conducted between October 1988 and March 2015, four hundred seventy-three liver transplants were performed at our institution. Of these, 231 were pediatric and 242 were adult. Among these patients, liver transplant was performed in 58 patients (12.3%) for treatment of hepatocellular carcinoma. RESULTS Hepatocellular carcinoma recurrence was detected in 14 patients (24.1%). Overall 5-year and 10-year survival rates of patients underwent liver transplant beyond the Milan criteria for hepatocellular carcinoma were 50.3% and 43.1%. Overall, 5- and 10-year survival rates of patients underwent liver transplant within the Milan criteria for hepatocellular carcinoma were 78.4% and 72.6%. The main predictive variable was whether the tumor had expensed beyond the Milan criteria. CONCLUSIONS As expected, outcomes were significantly better in the Milan criteria group. Although the overall- and disease-free survival rates were promising in such a group of patients who had no better chance, it could be asserted that liver transplant is a safe and effective treatment option with promising results, even if the tumor expanse is beyond the Milan criteria.
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Affiliation(s)
- Gokhan Moray
- From the Department of General Surgery and Transplantation, Baskent University School of Medicine, Ankara, Turkey
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10
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Redaelli D, Guraya SS. Primary hemangioendothelioma of liver; report of a case and review of literature. J Taibah Univ Med Sci 2015. [DOI: 10.1016/j.jtumed.2014.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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11
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Suh KS, Lee HW. Liver transplantation for advanced hepatocellular carcinoma: how far can we go? Hepat Oncol 2015; 2:19-28. [PMID: 30190984 DOI: 10.2217/hep.14.34] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Liver transplantation is one of the most effective treatment options for hepatocellular carcinoma. Although the Milan criteria have been widely used to identify suitable candidates for liver transplant with a good prognosis, many transplant centers have developed and actually used more expanded criteria. Living donor liver transplant (LDLT) is at the center of expansion of criteria because it is based on the personal relationship between a recipient and a donor. Asian LDLT centers have developed various expanded criteria for LDLT using tumor biologic markers as well as the size and number of the tumors. However, there is no consensus on the limit of the expansion of criteria. Here, we present our experience and opinion on LDLT for advanced hepatocellular carcinoma.
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Affiliation(s)
- Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Department of Surgery, Seoul National University Boramae Medical Center, Seoul, South Korea.,Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Department of Surgery, Seoul National University Boramae Medical Center, Seoul, South Korea
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12
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Singal A, Welling TH, Marrero JA. Role of liver transplantation in the treatment of cholangiocarcinoma. Expert Rev Anticancer Ther 2014; 9:491-502. [DOI: 10.1586/era.09.5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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13
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Abstract
Vascular sarcomas are soft-tissue tumors that arise from the endothelium with a malignant potential. This review discusses the management of epithelioid hemangioendothelioma (EHE) and angiosarcoma. EHE is a vascular tumor of intermediate malignant potential with an indolent course. EHE arising from the liver, lung, or bone tends to be multifocal and the rate of progression is slow and often unpredictable. Treatment should be considered in patients with significant symptomatic deterioration and/or progressive disease on imaging studies. Various cytotoxic and targeted therapies are available for management, with disease stabilization as the most common outcome. Angiosarcoma is an aggressive vascular tumor with a high malignant potential. Multidisciplinary care is critical for the management of localized disease, and the best outcomes are often observed in patients when a combination of systemic and local therapy options is used. Metastatic angiosarcoma is treated primarily with systemic therapy, and several cytotoxic and targeted therapies are available, alone or in combination. The choice of therapy depends on several factors, such as cutaneous location of the tumor, performance status of the patient, toxicity of the treatment, and patient goals.
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Affiliation(s)
- Vinod Ravi
- Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 450, Houston, TX 77030, USA.
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14
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Lei J, Wang W, Yan L. Downstaging advanced hepatocellular carcinoma to the Milan criteria may provide a comparable outcome to conventional Milan criteria. J Gastrointest Surg 2013; 17:1440-6. [PMID: 23719776 DOI: 10.1007/s11605-013-2229-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 05/06/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Many hepatocellular carcinoma (HCC) patients met the appropriate criteria and accepted liver transplantation after successful downstaging therapies; however, the outcome in these patients is unclear. We aim to compare the outcome of patients meeting the Milan criteria at the beginning and after successful downstaging therapies. PATIENTS AND METHODS Between July 2001 and January 2013, 112 patients were diagnosed with early-stage HCC that met the Milan criteria. Of these patients, 58 patients did not meet the Milan criteria initially but did after successful downstaging therapies. We retrospectively collected and then compared the baseline characteristics, postoperative complications, survival rate, and tumor recurrence rate of these two groups. Kaplan-Meier analyses were used to estimate the long-term overall survival and tumor-free survival in these patients. RESULTS No significant differences were observed between the two groups with respect to baseline donor and recipient characteristics. The downstaging Milan group showed similar tumor characteristics compared to the conventional Milan group, except the downstaging group had better tumor histopathologic grading (P = 0.027). The 1-, 3-, and 5-year overall survival rates were comparable at 91.4, 82.8, and 70.7 %, respectively, in the downstaging Milan criteria and 92.0, 85.7, and 74.1 %, respectively, according to the initial Milan criteria (P = 0.540). The 1-, 3-, and 5-year tumor-free survival rates between the two groups were not statistically significant (P = 0.667). CONCLUSION Successful downstaging therapies can provide a comparable posttransplantation overall survival and tumor-free survival rates after liver transplantation.
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Affiliation(s)
- Jianyong Lei
- Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
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15
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Fujiki M, Aucejo F, Kim R. Adjuvant treatment of hepatocellular carcinoma after orthotopic liver transplantation: do we really need this? Clin Transplant 2012; 27:169-77. [PMID: 23216662 DOI: 10.1111/ctr.12042] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2012] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) continues to rise and is still a major cause of mortality. Orthotopic liver transplantation (OLT) continues to give patients the best chance for cure, but recurrence of the disease remains a problem. Even with the implementation of the Milan criteria, recurrence rates have been shown to be 8-15% in most studies and even higher in patients who are beyond the Milan criteria. Therefore, several investigators have looked into the value of adjuvant therapy using systemic cytotoxic chemotherapy in HCC after OLT. Unfortunately, most of the trials are very small, and the results have been disappointing. But trials using Licartin seem to be promising, and other drugs such as FOLFOX and sorafenib warrant further investigation based on their efficacy in the advanced disease. In this review, we will review the current data on efficacy and rationale of adjuvant treatment for HCC after OLT including novel biomarkers.
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Affiliation(s)
- M Fujiki
- Liver Transplantation and Hepatobiliary Surgery, Cleveland Clinic, Cleveland, OH, USA
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16
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Agrawal N, Parajuli S, Zhao P, Satoskar R, Laurin J, Azumi N, Matsumoto C, Shetty K. Liver transplantation in the management of hepatic epithelioid hemangioendothelioma: a single-center experience and review of the literature. Transplant Proc 2012; 43:2647-50. [PMID: 21911139 DOI: 10.1016/j.transproceed.2011.06.035] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Accepted: 06/03/2011] [Indexed: 12/12/2022]
Abstract
Hepatic epitheliod hemangioendothelioma (HEHE) is a rare tumor of vascular origin with unpredictable malignant potential. We describe our experience with four biopsy-proven HEHE cases that were considered for orthotopic liver transplant (OLT). Three patients had preserved hepatic function and despite extensive disease burden did not develop disease progression while awaiting OLT. We were able to utilize the review process allowed by United Network of Organ Sharing to obtain additional priority for OLT for these patients. This led to expedited organ allocation and excellent post-OLT outcomes.
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Affiliation(s)
- N Agrawal
- Georgetown Transplant Institute, Georgetown University Hospital, Washington, DC 20007, USA
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Frilling A, Malago M, Testa G, Schleyer E, Grabellus F, Kronenberger R, Li J, Broelsch CE. Liver transplantation for metastasized extragastrointestinal stromal tumor: a case report and an overview of literature. Transplant Proc 2011; 42:3843-8. [PMID: 21094867 DOI: 10.1016/j.transproceed.2010.06.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2010] [Accepted: 06/18/2010] [Indexed: 11/29/2022]
Abstract
A 63-year-old woman underwent living donor liver transplantation for hepatic metastases of an extragastrointestinal stromal tumor (EGIST) originating from the rectovaginal space. Due to a multifocal extrahepatic tumor recurrence, treatment with imatinib mesylate was started after extensive pharmacokinetic studies to rule out possible interactions with immunosuppressives. We performed several re- resections for EGIST recurrence thereafter. At the last follow-up, 17 years after primary tumor resection and 10 years after living donor liver transplantation, the patient is symptom-free under immunosuppressive and imatinib mesylate treatments with a 2-cm stable recurrent pararectal EGIST. To our knowledge, this is the only report published on a patient who underwent transplantation for hepatic EGIST metastases with a posttransplantation follow-up of 10 years and the first report on living donor liver transplantation for metastasized EGIST. This is the first description of pharmacokinetics of imatinib and its main active metabolite CGP74588 in a liver transplant recipient.
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Affiliation(s)
- A Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
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18
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Sieghart W, Wang X, Schmid K, Pinter M, König F, Bodingbauer M, Wrba F, Rasoul-Rockenschaub S, Peck-Radosavljevic M. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol 2011; 54:89-97. [PMID: 20970216 DOI: 10.1016/j.jhep.2010.06.030] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2009] [Revised: 06/16/2010] [Accepted: 06/18/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT. METHODS Osteopontin expression was investigated immunohistochemically in a unique population of 125 HCC-patients undergoing OLT between 1982 and 2002, including 81 patients (65%) outside the Milan criteria. Multivariate analysis of factors associated with median overall survival (OS) and time to recurrence (TTR) was performed. RESULTS Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5 years was 77%, 62%, 52%, and 43% (median survival 37 months). Overall survival was significantly longer without expression of OPN (p < 0.05; (median OS: 56 vs. 23 months). The same was true for median TTR (p = 0.008). Outside Milan criteria, patients without OPN-expression had better prognosis (median OS: 37.8 vs. 19.2 months, p = 0.003). Tumor recurrence in patients transplanted outside Milan criteria occurred in 43% (23 of 54) of patients without and 70% (19 of 27, p = 0.018) of patients with OPN-expression after a median TTR of 83.5 vs. 13.9 months. On multivariate analysis, vascular invasion and OPN-expression were independently associated with OS and TTR in HCC-patients after OLT. CONCLUSIONS Immunohistochemically detectable Osteopontin in HCC is an independent predictor of tumor recurrence and survival in patients beyond Milan criteria undergoing OLT.
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Affiliation(s)
- Wolfgang Sieghart
- Abteilung Gastroenterologie and Hepatologie, Medizinische Universität and AKH Wien, Vienna, Austria
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Mailey B, Buchberg B, Prendergast C, Artinyan A, Khalili J, Sanchez-Luege N, Colquhoun SD, Kim J. A disease-based comparison of liver transplantation outcomes. Am Surg 2009; 75:901-8. [PMID: 19886131 DOI: 10.1177/000313480907501008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
An increasing demand for transplant donor organs has made optimal allocation of resources a priority. Our objective was to evaluate outcomes for orthotopic liver transplantation (OLT) performed in the United States. A query of the United Network for Organ Sharing registry between 1988 and 2007 was performed for patients who underwent OLT for all etiologies. Patients were stratified by pathology necessitating OLT and clinical and pathologic factors were compared. Multivariate Cox-regression analysis was used to assess the association of pathology with survival. Of 61,823 patients, 33 per cent (n = 20,305) of OLTs were secondary to hepatitis C virus, 21 per cent autoimmune disease, 17 per cent alcohol-induced injury, 11 per cent cryptogenic cirrhosis, 8 per cent hepatocellular carcinoma (HCC), 6 per cent hepatitis B virus, and 4 per cent metabolic disease. Patients with autoimmune disease and HCC demonstrated the best and worst survival, respectively, after OLT (median survival 16.0 vs 6.4 yrs, respectively, P < 0.001). By multivariate analysis, OLT for HCC was significantly associated with poorer overall survival (hazard ratio [HR] 2.19, 95% confidence interval [CI]: 2.02-2.37, P < 0.001). Our results indicate that outcomes for liver transplantation vary by primary hepatic pathology with HCC patients having the poorest overall survival. To optimize organ allocation for all patients with end-stage liver disease, a better understanding of poor survival for HCC is necessary.
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Affiliation(s)
- Brian Mailey
- Department of Oncologic Surgery, City of Hope, Duarte, California 91010, USA
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Li J, Yan LN, Yang J, Chen ZY, Li B, Zeng Y, Wen TF, Zhao JC, Wang WT, Yang JY, Xu MQ, Ma YK. Indicators of prognosis after liver transplantation in Chinese hepatocellular carcinoma patients. World J Gastroenterol 2009; 15:4170-6. [PMID: 19725152 PMCID: PMC2738814 DOI: 10.3748/wjg.15.4170] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify prognostic factors of patients with hepatocellular carcinoma (HCC), who were treated by orthotopic liver transplantation (OLT).
METHODS: From January 2000 to October 2006, 165 patients with HCC underwent OLT. Various clinicopathological risk factors for actuarial and recurrence-free survival were identified using the Kaplan-Meier method with the log-rank test. The Cox proportional hazards model was used to identify independently predictive factors for actuarial and recurrence-free survival, which were used to propose new selection criteria. We compared the outcome of the subgroup patients meeting different criteria. Survival analysis was performed using the Kaplan-Meier method with the log-rank test.
RESULTS: The median follow-up was 13.0 mo (2.8-69.5 mo). Overall, 1-, 2-, 3- and 5-year actuarial survival was 73.3%, 45.6%, 35.4% and 32.1%, respectively. One-, 2-, 3- and 5-year overall recurrence-free survival was 67.0%, 44.3%, 34.5% and 34.5%, respectively. In univariate analysis, number of tumors, total tumor size, lobar distribution, differentiation, macrovascular invasion, microvascular invasion, capsulation of the tumor, and lymph node metastasis were found to be associated significantly with actuarial and tumor-free survival. By means of using the multivariate Cox proportional hazards model, total tumor size and macrovascular invasion were found to be independent predictors of actuarial and tumor-free survival. When the selection criteria were expanded into the proposed criteria, there was no significant difference in 1-, 2-, 3- and 5-year actuarial and tumor-free survival of the 49 patients who met the proposed criteria (97.6%, 82.8%, 82.8% and 82.8%, and 90.7%, 82.8%, 68.8% and 68.8%, respectively) compared with that of patients who met the Milan or University of California, San Francisco (UCSF) criteria.
CONCLUSION: Macrovascular invasion and total tumor diameter are the strongest prognostic factors. The proposed criteria do not adversely affect the outcome of liver transplantation for HCC, compared with the Milan or UCSF criteria.
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Kirchner GI, Tischendorf JJW, Bleck J, Wagner S, Caselitz M, Klempnauer J, Manns MP, Gebel M, Gebel M. Perihilar lymph nodes in patients with primary sclerosing cholangitis with and without cholangiocellular carcinoma. Scand J Gastroenterol 2009; 43:1366-70. [PMID: 18609164 DOI: 10.1080/00365520802200002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Enlarged perihilar lymph nodes have been described in patients with primary sclerosing cholangitis (PSC). The aim of the study was to determine the clinical relevance of perihilar lymph nodes in PSC patients with and without cholangiocellular carcinoma (CCC). MATERIAL AND METHODS The status of perihilar lymph nodes was investigated in 117 patients with PSC using "high-end" ultrasound. Thirty-five of the 117 PSC patients had histologically proven CCC. Lymph node status was correlated with the presence of CCC and inflammatory bowel disease (IBD). RESULTS Seventy-three percent of PSC patients without CCC and 86% of patients with CCC had enlarged perihilar lymph nodes (NS). In CCC patients, the width of lymph nodes was significantly larger (12+/-6 mm versus 8+/-4 mm; p=0.0001), and the length:width ratio (2.15+/-0.7:1 versus 2.5+/-0.6:1; p=0.004) of the lymph nodes was significantly lower. Thirty-seven percent of PSC patients without CCC and 57% of patients with PSC and CCC had multiple perihilar lymph nodes (p=0.04). In all patients, the presence versus absence of IBD had no influence on the number (84% versus 74%,) and size of perihilar lymph nodes (length: 21+/-10 mm versus 19+/-7 mm). Lymph node status did not correlate with the number of episodes of cholangitis. CONCLUSIONS Enlarged perihilar lymph nodes are characteristic of patients with PSC. Since perihilar lymph nodes are not predictive of the presence of complicating CCC, such patients should not be excluded from liver transplantation.
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Affiliation(s)
- Gabriele I Kirchner
- Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany.
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Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G, Vivarelli M, Golfieri R, D'Errico Grigioni A, Panzini I, Morelli C, Bernardi M, Bolondi L, Pinna AD. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 2008; 8:2547-57. [PMID: 19032223 DOI: 10.1111/j.1600-6143.2008.02409.x] [Citation(s) in RCA: 292] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC <or= 5 cm or less than or equal to three HCCs <or= 3 cm. We prospectively evaluated the possibility of slightly extending these criteria in a down-staging protocol, which included patients initially outside conventional criteria: single HCC 5-6 cm or two HCCs <or= 5 cm or less than six HCCs <or= 4 cm and sum diameter <or= 12 cm, but within Milan criteria in the active tumors after the down-staging procedures. The outcome of patients down-staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention-to-treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down-staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow-up of 2.5 years after transplantation, the 1 and 3 years' disease-free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down-staging. The actuarial intention-to-treat survival was 27/48 patients (56.3%) in the down-staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down-staging criteria provide a comparable outcome to the conventional criteria.
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Affiliation(s)
- M Ravaioli
- Department of Liver and Multi-organ Transplantation, Pathology Division of the F. Addarii Institute, Sant' Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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24
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Yao FY, Kerlan RK, Hirose R, Davern TJ, Bass NM, Feng S, Peters M, Terrault N, Freise CE, Ascher NL, Roberts JP. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 2008; 48:819-27. [PMID: 18688876 PMCID: PMC4142499 DOI: 10.1002/hep.22412] [Citation(s) in RCA: 405] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
UNLABELLED We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2-5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceeding T2 criteria who were enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein >1,000 ng/mL. CONCLUSION Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome.
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Affiliation(s)
- Francis Y. Yao
- Department of Medicine, University of California, San Francisco, San Francisco, CA,Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Robert K. Kerlan
- Department of Radiology, University of California, San Francisco, San Francisco, CA
| | - Ryutaro Hirose
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Timothy J. Davern
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Nathan M. Bass
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Sandy Feng
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Marion Peters
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Norah Terrault
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Chris E. Freise
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Nancy L. Ascher
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John P. Roberts
- Department of Surgery, University of California, San Francisco, San Francisco, CA
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Woo HY, Jang JW, Choi JY, You CR, Jeong SW, Bae SH, Yoon SK, Lee YS, Kim DG. Living donor liver transplantation in hepatocellular carcinoma beyond the Milan criteria. Liver Int 2008; 28:1120-8. [PMID: 18492023 DOI: 10.1111/j.1478-3231.2008.01785.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND/AIMS In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria. METHODS Pre-operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated. RESULTS The 1- and 3-year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface (P=0.014) and progressive disease after pretransplant treatment (P=0.038). The 2-year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively (P<0.001). The 2-year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors (P=0.022). CONCLUSIONS In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface.
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Affiliation(s)
- Hyun Young Woo
- Department of Internal Medicine, Liver Transplantation Center, Division of Hepatology, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Szavay PO, Luithle T, Warmann SW, Geerlings H, Ure BM, Fuchs J. Impact of pedicle clamping in pediatric liver resection. Surg Oncol 2008; 17:17-22. [PMID: 17855078 DOI: 10.1016/j.suronc.2007.08.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2007] [Revised: 07/17/2007] [Indexed: 11/21/2022]
Abstract
BACKGROUND Vascular clamping techniques are commonly used but so far the impact on pediatric liver surgery has not been investigated. The purpose of this study was to analyze pedicle clamping during pediatric liver resection in terms of hepato-cellular injury and blood loss. METHODS Sixty-seven children undergoing liver resection were analyzed retrospectively. Vascular clamping was used in 28 cases (PC group), in 39 the resection was performed without clamping (NPC group). Major hepatectomies (resection of more than three segments) were carried out in 88%, minor hepatectomies (resection of three and less segments) in 12% of patients. Twenty-six children underwent extended liver resection. Patient data, liver function tests (LFTs) and blood loss were analyzed statistically. RESULTS There were no significant differences in patient preoperative and postoperative data and LFTs between the groups. Within the NPC group the amount of administered fresh frozen plasma (FFP) in total and per kilogram (FFP/kg) was significantly higher (p=0.023 and 0.028) than in the PC group. For patients with extended liver resection, operation times were significantly longer (p=0.016) in the group without vascular clamping (NPCext). In the NPCext group significantly more children required packed red cells, FFP and FFP/kg. LFTs showed no significant differences in all children regardless of vascular clamping. CONCLUSIONS For children undergoing liver resection, vascular clamping offers a blood saving surgical technique. Postoperative LFTs were not statistically different, regardless of vascular clamping. Pedicle clamping proved to be a safe method, not associated with an increase in perioperative complications.
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Affiliation(s)
- Philipp O Szavay
- Department of Pediatric Surgery, Children's Hospital, University of Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany.
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The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry. Ann Surg 2008; 246:949-57; discussion 957. [PMID: 18043096 DOI: 10.1097/sla.0b013e31815c2a70] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. MATERIAL AND METHODS Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT. RESULTS HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. CONCLUSIONS The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.
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Liver Transplantation. Surgery 2008. [DOI: 10.1007/978-0-387-68113-9_86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Fisher RA, Maluf DG, Wolfe L, Williams B, Cotterell A, Stravitz RT, Heuman D, Posner M. Is hepatic transplantation justified for primary liver cancer? J Surg Oncol 2007; 95:674-9. [PMID: 17477383 DOI: 10.1002/jso.20617] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
A concise, yet objective overview of Hepatocellular Carcinoma (HCC) treatment in 2006 with an intent to transplant is presented. The most significant variables impacting on the use of hepatic transplantation as therapy for primary liver cancer are developed under the headings of: Staging Criteria; Organ allocation; Transplant dropout minimization therapies; and Effects on the HCC general population. The pertinent medical literature and update of an ongoing intent-to-treat HCC with transplant single center randomized control trial are reviewed.
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Affiliation(s)
- Robert A Fisher
- Department of Surgery, Division of Transplant Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
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Girard N, Mornex F, Trepo C, Merle P. Place de la radiothérapie dans la stratégie de traitement du carcinome hépatocellulaire. ONCOLOGIE 2007. [DOI: 10.1007/s10269-007-0650-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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31
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Millonig G, Graziadei IW, Freund MC, Jaschke W, Stadlmann S, Ladurner R, Margreiter R, Vogel W. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2007; 13:272-9. [PMID: 17256758 DOI: 10.1002/lt.21033] [Citation(s) in RCA: 187] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Patients with small hepatocellular carcinoma (HCC) can be cured by liver transplantation (LT). However, many patients drop out during the waiting time as a result of tumor progression. We prospectively investigated the effect of transarterial chemoembolization on long-term survival of 116 patients with HCC listed for LT. Intention-to-treat analysis revealed that patients with either complete or partial response to therapy (no vital tumor or devascularization of > or =30%, respectively) as assessed by computed tomographic scan before LT had far better 1-, 2-, and 5-year survival rates (100, 93.2, and 85.7%; and 93.8, 83.6, and 66.2%, respectively) compared with those with no response or with tumor progression (82.4, 50.7, and 19.3%). Posttransplant survival analysis showed a marked survival benefit according to transarterial chemoembolization response: patients with complete or partial response had 1-, 2-, and 5-year survival rates of 89.1, 85.1, and 85.1%, and 88.6, 77.4, and 63.9%, respectively, compared with 68.6, 51.4, and 51.4% for patients whose disease did not respond to therapy. Subgroup analysis, however, showed that these benefits were only seen in patients whose disease met the Milan criteria, but not in disease exceeding the Milan criteria but fitting the expanded University of California at San Francisco criteria. These patients were also more likely to drop out as a result of tumor progression while waiting for LT (dropout rate 12.1 vs. 2.9%) and to develop recurrent HCC (21.6 vs. 7.6%). Downstaged patients did even worse, with a dropout rate of 26.7% and a 5-year survival rate of only 25%. In conclusion, the response to preoperative chemoembolization may predict long-term outcome after LT.
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Affiliation(s)
- Gunda Millonig
- Divisions of Gastroenterology and Hepatology, Medical University of Innsbruck, Austria
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Suh KS, Cho EH, Lee HW, Shin WY, Yi NJ, Lee KU. Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria. Dig Dis 2007; 25:329-33. [PMID: 17960068 DOI: 10.1159/000106913] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND To expand the Milan criteria, prognostic factors other than size and number of tumor may be necessary. We analyzed outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) exceeding Milan criteria to select favorable group of patients. METHODS Between November 1997 and December 2005, 104 cases of liver transplantation for patients with HCC were performed at our center. Twenty-four patients did not meet the Milan criteria preoperatively. Among these 24 patients, 19 had no major vascular invasion at the time of surgery. We analyzed the survival and prognostic factors of these 19 patients. The mean follow-up period was 33 months (range 6-89). RESULTS Three-year survival rate in 19 patients was 67.4%. Three-year survival rates were significantly higher when preoperative alpha-fetoprotein was less than 400 ng/ml (86.2 vs. 0%, p<0.001) when Edmonson-Steiner's histological grade 1 or 2 (100 vs. 40%, p = 0.036) and when microvascular invasion was absent (78.6 vs. 30%, p = 0.039). CONCLUSION If vascular invasion is absent in preoperative radiological studies, and the preoperative alpha-fetoprotein is less than 400 ng/ml, our findings suggest a good prognosis after liver transplantation for HCC patients who do not meet the Milan criteria.
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Affiliation(s)
- Kyung-Suk Suh
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Korea.
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Mehrabi A, Kashfi A, Fonouni H, Schemmer P, Schmied BM, Hallscheidt P, Schirmacher P, Weitz J, Friess H, Buchler MW, Schmidt J. Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy. Cancer 2006; 107:2108-21. [PMID: 17019735 DOI: 10.1002/cncr.22225] [Citation(s) in RCA: 299] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant tumor of vascular origin with unknown etiology and a variable natural course. The authors present a comprehensive review of the literature on HEH with a focus on clinical outcome after different therapeutic strategies. All published series on patients with HEH (n = 434 patients) were analyzed from the first description in 1984 to the current literature. The reviewed parameters included demographic data, clinical manifestations, therapeutic modalities, and clinical outcome. The mean age of patients with HEH was 41.7 years, and the male-to-female ratio was 2:3. The most common clinical manifestations were right upper quadrant pain, hepatomegaly, and weight loss. Most patients presented with multifocal tumor that involved both lobes of the liver. Lung, peritoneum, lymph nodes, and bone were the most common sites of extrahepatic involvement at the time of diagnosis. The most common management has been liver transplantation (LTx) (44.8% of patients), followed by no treatment (24.8% of patients), chemotherapy or radiotherapy (21% of patients), and liver resection (LRx) (9.4% of patients). The 1-year and 5-year patient survival rates were 96% and 54.5%, respectively, after LTx; 39.3% and 4.5%, respectively, after no treatment, 73.3% and 30%, respectively, after chemotherapy or radiotherapy; and 100% and 75%, respectively, after LRx. LRx has been the treatment of choice in patients with resectable HEH. However, LTx has been proposed as the treatment of choice because of the hepatic multicentricity of HEH. In addition, LTx is an acceptable option for patients who have HEH with extrahepatic manifestation. Highly selected patients may be able to undergo living-donor LTx, preserving the donor pool. The role of different adjuvant therapies for patients with HEH remains to be determined.
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Affiliation(s)
- Arianeb Mehrabi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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Abstract
Although wide surgical resection is the optimal curative therapy for carcinoid tumors, in most patients the presence of metastatic disease at diagnosis usually renders excision a palliative procedure. This nevertheless decreases tumor burden, facilitates symptom control, and prevents complications caused by bleeding, perforation, or bowel obstruction resulting from fibrosis. In the stomach (types I and II) and rectum endoscopic excision may be adequate provided the lesion(s) are local. Long-term therapy is focused on symptom alleviation and improvement of quality of life using somatostatin analogues, particularly in a subcutaneous depot formulation. In some instances interferons may have a role but their usage often is associated with substantial adverse events. Conventional chemotherapy and external radiotherapy either alone or in a variety of permutations are of minimal efficacy and should be balanced against the decrease in quality of life often engendered by such agents. Hepatic metastases may be amenable to surgery, radiofrequency ablation, or embolization either alone or in combination with chemotherapeutic agents or isotopically loaded microspheres. Rarely hepatic transplantation may be of benefit although controversy exists as to its actual use. Peptide-receptor-targeted radiotherapy for advanced disease using radiolabeled octapeptide analogs (111In/90Yt/177Lu-octreotide) appear promising but data are limited and its status remains investigational. A variety of antiangiogenesis and growth factor-targeted agents have been evaluated, but as yet have shown little promise. The keystone of current therapy remains the long-acting somatostatin analogues that alleviate symptomatology and substantially improve quality of life with minimal adverse effects.
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Affiliation(s)
- Irvin M Modlin
- Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
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Mansfield SD, Barakat O, Charnley RM, Jaques BC, O'Suilleabhain CB, Atherton PJ, Manas D. Management of hilar cholangiocarcinoma in the North of England: pathology, treatment, and outcome. World J Gastroenterol 2006; 11:7625-30. [PMID: 16437689 PMCID: PMC4723393 DOI: 10.3748/wjg.v11.i48.7625] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center. METHODS The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. RESULTS Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152 percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these, 36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05). Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions. CONCLUSION Resection increases survival but carries the risk of significant morbidity and mortality. Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.
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Affiliation(s)
- S D Mansfield
- Hepato-Pancreatico-Biliary Surgery Unit, Freeman Hospital, High Heaton, Newcastle upon Tyne, Tyne and Wear NE7 7DN, United Kingdom.
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Sauer P, Kraus TW, Schemmer P, Mehrabi A, Stremmel W, Buechler MW, Encke J. Liver Transplantation for Hepatocellular Carcinoma: Is there Evidence for Expanding the Selection Criteria? Transplantation 2005; 80:S105-8. [PMID: 16286885 DOI: 10.1097/01.tp.0000187107.64215.7b] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
A consequent application of the Milan criteria in patients undergoing liver transplantation for hepatocellular carcinoma (HCC) may lead to excellent long-term survival and a low incidence of recurrence. Expanding the selection criteria will result in more patients with hepatocellular carcinoma being potentially curative treated, but this approach is associated with at least a higher incidence of recurrence. Kaplan-Meier analysis of 110 patients, who underwent liver transplantation for HCC in our institution between 1987 and 2004, showed a significant improvement in patient survival with time. A change in criteria for patient selection may have contributed to the improved outcome. In 28 of 110 patients a recurrence of HCC was observed. In 82% of patients, who developed recurrence of carcinoma, the Milan criteria were not met. Dropout from the waiting list is common and several methods, including percutaneous ethanol injection, radiofrequency ablation, and chemoembolization, are used to prevent tumor progression and thus prevent dropout. As no randomized trials are available some uncertainty remains, whether these neoadjuvant procedures improve outcome. At present, there is no evidence that this approach enables expansion of the selection criteria. Hepatocellular carcinoma is a major indication for living related liver transplantation because the risk of dropout while waiting is negligible. Extension of the Milan criteria in the setting of living related liver transplantation may offer more patients a potentially curative treatment, without reducing the donor pool of organs for other patients on the waiting list with nonmalignant liver disease.
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Affiliation(s)
- Peter Sauer
- Department of Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
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Chen XP, Huang ZY. Surgical treatment of hepatocellular carcinoma in China: surgical techniques, indications, and outcomes. Langenbecks Arch Surg 2005; 390:259-65. [PMID: 15875211 DOI: 10.1007/s00423-005-0552-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2004] [Accepted: 01/19/2005] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Surgery remains the most effective treatment for hepatocellular carcinoma (HCC). While resection and liver transplantation achieve the best outcomes in patients with small HCC, controversy surrounds treatment of large HCC, HCC with portal vein tumor thrombus, and HCC with hypersplenism. PATIENT/METHODS From January 1988 to December 2002, 2,102 patients with large HCC underwent hepatectomy in our hospital. The traditional resection method was used on 959 patients, after which the improved new method was used on 1,143 patients. Meanwhile, from January 1990 until December 2003, hepatic resection +/- thrombectomy has been performed in 438 patients with HCC and portal vein tumor thrombus. Among them, 286 patients showed portal vein tumor thrombus located in the primary and secondary branch of the main portal vein (group A), and 152 patients showed portal vein tumor thrombus (PVTT) involved in the main portal vein (group B). Additionally, out of 204 HCC patients with cirrhotic hypersplenism, 94 patients had hepatectomy and splenectomy, and 100 patients had only hepatectomy without hospital death. RESULTS The 3- and 5-year survival after resection of large HCCs (over 5 cm) with improved new method in China was between 50.7 and 58.8% and 27.9 and 38.7%, respectively. Tumor recurrence in the liver within 1 year after hepatic resection + thrombectomie was detected in 45% of group A and in 78.8% in group B. The cumulative 5-year overall survival rates were 18.1% for group A and 0% for group B. The 1-, 3-, and 5-year overall survival in HCC plus portal vein tumor thrombus (PVTT) was 58.7, 22.7, and 18.1%. The hepatectomy/splenectomy group had a 5-year tumor-free survival rate of 37.2% and the hepatectomy group alone had 27.2%. CONCLUSION The new resection methods, hepatic resection + thrombectomy and hepatectomy + splenectomy, are very effective treatments for large HCC, HCC with portal vein tumor thrombus, and HCC with hypersplenism, respectively. Local treatment modalities, e.g. percutaneous ethanol injection, cryosurgery, and radiofrequency ablation as well as microwave coagulation are used in patients with poor liver function in small and large HCCs.
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Affiliation(s)
- Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China.
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Abstract
During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection.
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Affiliation(s)
- Ludger Barthelmes
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical SchoolDundeeUnited Kingdom
| | - Iain S. Tait
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical SchoolDundeeUnited Kingdom
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Ravaioli M, Ercolani G, Cescon M, Vetrone G, Voci C, Grigioni WF, D'Errico A, Ballardini G, Cavallari A, Grazi GL. Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria. Liver Transpl 2004; 10:1195-202. [PMID: 15350014 DOI: 10.1002/lt.20239] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of >1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5-year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5-year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients.
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Affiliation(s)
- Matteo Ravaioli
- Department of Surgery and Transplantation, Surgical Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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Marín-Hargreaves G, Azoulay D, Bismuth H. Hepatocellular carcinoma: surgical indications and results. Crit Rev Oncol Hematol 2003; 47:13-27. [PMID: 12853096 DOI: 10.1016/s1040-8428(02)00213-5] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a tumour of increasing incidence that usually arises in cirrhotic liver. Untreated, the prognosis is grim and the only curative treatment is surgical resection. The practical application of segmental surgery to the liver together with the use of ultrasound and other imaging techniques, patient selection criteria and improvements in perioperative technique and postoperative care have contributed to better results in hepatic surgery. Today, less than 10% mortality for resection of cirrhotic livers, with up to 50% 5-year survival rates are to be expected. However, the limits of resection for cure: intrahepatic recurrence makes stringent follow-up necessary. In this way the available modalities of treatment can be applied so as to improve survival. Herein, a current 'state-of-the-art' of surgical indications and results for HCC is given.
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Affiliation(s)
- Guillermo Marín-Hargreaves
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif et Université Paris-Sud, 12 avenue Paul Vaillant Couturier, 94800 Villejuif, Paris, France
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Graziadei IW, Sandmueller H, Waldenberger P, Koenigsrainer A, Nachbaur K, Jaschke W, Margreiter R, Vogel W. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl 2003; 9:557-63. [PMID: 12783395 DOI: 10.1053/jlts.2003.50106] [Citation(s) in RCA: 332] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Orthotopic liver transplantation (OLT) has been considered the best treatment option for patients with hepatocellular carcinoma (HCC). Because of a steadily increasing waiting time, a noteworthy proportion of patients are excluded from OLT because of tumor progression. A 20% and more dropout rate from the waiting list has recently been reported. In this prospective study, we evaluated the effect of preoperative transarterial chemoembolization (TACE) on preventing tumor progression while on the waiting list in patients meeting current selection criteria (solitary lesion < or = 5 cm, three lesions < or = 3 cm). In addition, we analyzed the outcome of a separate group of patients with advanced-stage HCC outside the selection criteria but with at least 50% tumor reduction after TACE (downstaging) to expand current criteria. Forty-eight patients met the selection criteria and were eligible for this study. Seven patients are still on the waiting list; 41 underwent OLT. None of these patients had to be removed from the list because of tumor progression after a mean waiting time of 178 days (23 patients > or =180 days). The 1-, 2-, and 5-year intention-to-treat survival was 98%, 98%, and 94%. The outcome after OLT was also excellent with 1-, 2-, and 5-year survival rates of 98%, 98%, and 93%. Tumor recurrence occurred only in 1 patient (2.4%). Fifteen patients with advanced-stage HCC were included in this study. Three developed a tumor progression and had to be removed from the list (20% dropout rate). Despite tumor reduction before OLT, these patients had a significantly less favorable outcome in the intention-to-treat analysis as well as in the posttransplantation survival. Tumor recurrence was seen in 30% of patients after OLT. In conclusion, TACE followed by OLT is associated with an excellent outcome in selected patients. Furthermore, TACE is highly efficacious in preventing tumor progression while waiting for OLT. Although TACE reduced tumor preoperatively, it failed to show a beneficial effect on patient survival in advanced-stage HCCs.
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Affiliation(s)
- Ivo W Graziadei
- Department of Gastroenterology and Hepatology, University Hospitals Innsbruck, Austria.
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Yoon JH, Gores GJ. Diagnosis, Staging, and Treatment of Cholangiocarcinoma. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2003; 6:105-112. [PMID: 12628069 DOI: 10.1007/s11938-003-0011-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Attention has to be focused on earlier detection of cholangiocarcinoma, especially in high-risk patients such as those with primary sclerosing cholangitis (PSC). Enhanced techniques for diagnosing this disease include imaging studies such as positron emission tomography (PET) scanning, and cytologic analysis including digital image analysis (DIA) and fluorescent in situ hybridization (FISH). Magnetic resonance imaging and endoscopic ultrasonography have also improved and simplified preoperative staging. Despite recent advances in the endoscopic management of cholangiocarcinoma, this neoplastic disease is still fatal in the majority of patients. Surgical resection or liver transplantation offers the only possibility for curing this disease in its early stages. However, most patients present with advanced disease that is not amenable to such therapy. For those patients presenting with unresectable carcinoma above the cystic duct without intrahepatic or extrahepatic metastases, orthotopic liver transplantation combined with preoperative irradiation and chemotherapy is available and demonstrates improved survival on the basis of a recent study conducted at the Mayo Clinic. In the future, chemopreventive strategies aimed at blocking the links between inflammation (eg, nitric oxide synthase and cylcooxygenase 2 inhibitors) and carcinogenesis may help prevent this often fatal disease in high-risk patients (eg, patients with PSC).
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Affiliation(s)
- Jung-Hwan Yoon
- Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
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Abstract
BACKGROUND Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. AIMS To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. METHOD Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment-resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. RESULTS Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8-6.1 months with an acceptable cost (US dollars 40,000/ year of life gained) for waiting lists > or = 1 year whereas it was not cost effective (US dollars 74,000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2-6.7 months with a marginal cost of approximately US dollars 20,000/year of life gained in all cases, remaining cost effective for all waiting times. CONCLUSIONS Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage.
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Moya A, Berenguer M, Aguilera V, Juan FS, Nicolás D, Pastor M, López-Andujar R, Rayón M, Orbis F, Mora J, De Juan M, Carrasco D, Vila JJ, Prieto M, Berenguer J, Mir J. Hepatocellular carcinoma: Can it be considered a controversial indication for liver transplantation in centers with high rates of hepatitis C? Liver Transpl 2002; 8:1020-7. [PMID: 12424715 DOI: 10.1053/jlts.2002.35664] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is still considered a controversial indication for liver transplantation (LT), mainly because of long waiting times and underlying viral cirrhosis. The goal was to evaluate the outcome of LT in 104 patients with HCC and cirrhosis, mainly hepatitis C virus (HCV)-related, in a center with a short waiting time (median, 105 days). Four groups were formed according to the HCC and HCV status: HCV positive with HCC (group 1, n = 81), HCV negative with HCC (group 2, n = 23), HCV positive without HCC (group 3, n = 200), and HCV negative without HCC (group 4, n = 207). Predictive factors of tumor recurrence were demographics, tumor related (size or number of nodules, capsule, bilobar involvement, vascular or lymphatic invasion, clinical and pathologic TNM staging, pre-LT percutaneous ultrasound-guided ethanol injection or transarterial chemoembolization, alpha-fetoprotein levels), donor and surgery related, and year of transplantation. The same variables and "tumor recurrence (yes/no)" were applied to evaluate the effect on survival. The median follow up was 29 months (range, 0 to 104 months). Patient survival was 70% at 1 year and 59% at 5 years for group 1, 87% at 1 year and 77% at 5 years for group 2, 81% at 1 year and 64% at 5 years for group 3, and 88% at 1 year and 77% at 5 years for group 4 (P =.013). Survival was significantly lower in patients with HCC than in those without (74% and 63% versus 85% and 70%, at 1 and 5 years, respectively; P =.05). The causes of death in those with and without HCC were tumor recurrence (24%) and recurrent HCV (8%) versus sepsis (34%) and recurrent HCV (14%). HCC recurrence occurred in 12 patients (11.5%) at a median of 14 months (range, 3 to 60 months) with a probability increasing from 8% at 1 year to 16% at 5 years. In patients with HCC, tumor recurrence was associated with vascular invasion (P =.0004) by multivariate analysis; variables predictive of survival were donor old age (P =.01), viral-related etiology (P =.02), and tumor recurrence (P =.001). Although LT still remains an adequate indication for HCC in centers with high prevalence of HCV infection and short waiting times, both tumor and HCV-related recurrent diseases hamper significantly the outcomes of these patients.
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Affiliation(s)
- Angel Moya
- Department of Surgery, Hospital Universitario La Fe, Valencia, Spain.
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Abstract
Liver transplantation is an established treatment modality for patients with hepatocellular carcinoma (HCC), creating a potential for disease-free, long-term survival. In Asia, due to a severe shortage of donors, resection remains the treatment of choice for patients with HCC and good liver functional reserve. The use of marginal donors, split liver grafts and grafts from living donors are potential solutions that are best performed in experienced liver transplant centres to ensure an optimal outcome. Ethical issues relating to living donor liver transplantation have yet to be fully addressed. The roles of therapies to limit tumour progression during the waiting period, such as transarterial chemoembolization, need to be further investigated in the setting of a prospective trial and their benefits better defined.
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Affiliation(s)
- Kenneth S W Mak
- Liver Transplant Unit, National University Hospital, Singapore.
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47
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Okuda K, Nakanuma Y, Miyazaki M. Cholangiocarcinoma: recent progress. Part 2: molecular pathology and treatment. J Gastroenterol Hepatol 2002; 17:1056-63. [PMID: 12201864 DOI: 10.1046/j.1440-1746.2002.02780.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Part 2 of this review discusses DNA damage in biliary epithelial cells in the development of cholangiocarcinoma, alterations in cell kinetics of biliary epithelial cells, biliary epithelial mitoinhibition, and apoptosis that includes the role of Bcl-2, transforming growth factor-beta, telomerase activities and deregulation of Ras and p53, cancer-associated antigens in cholangiocarcinoma, precancerous lesions, stroma formation and angiogenesis, cancer invasion, cell-cell and cell-matrix interactions, and the mechanism of evasion from immune surveillance. These discussions are followed briefly by treatments such as photodynamic therapy, and surgical approaches comparing resection and liver transplantation.
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Affiliation(s)
- Kunio Okuda
- Department of Medicine, Chiba University School of Medicine, Chiba, Japan.
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48
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Molmenti EP, Klintmalm GB. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry. Liver Transpl 2002; 8:736-48. [PMID: 12200772 DOI: 10.1053/jlts.2002.34879] [Citation(s) in RCA: 103] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor.
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Affiliation(s)
- Ernesto P Molmenti
- Baylor University Medical Center, Transplantation Services, Dallas, TX 75246, USA
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Fuchs J, Rydzynski J, Von Schweinitz D, Bode U, Hecker H, Weinel P, Bürger D, Harms D, Erttmann R, Oldhafer K, Mildenberger H. Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94. Cancer 2002; 95:172-82. [PMID: 12115331 DOI: 10.1002/cncr.10632] [Citation(s) in RCA: 161] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND In the past 20 years, a dramatic improvement in the prognosis of patients with hepatoblastoma (HB) has been achieved by combining surgery with chemotherapy in several national and international trials. A worldwide, unsolved problem remains the treatment of patients with advanced or metastatic HB. METHODS The German Cooperative Pediatric Liver Tumor Study HB 94 was a prospective, multicenter, single-arm study. The study ran from January 1994 to December 1998. The protocol assessed the efficiency of chemotherapy consisting of cisplatin, ifosfamide, and doxorubicin (CDDP/IFO/DOXO) and/or etoposide and carboplatin (VP16/CARBO). The prognostic significance of the surgical strategy, pretreatment factors, and tumor characteristics for disease free survival (DFS) were analyzed. RESULTS Sixty-nine children with HB were treated in the HB 94 study. The median follow-up of survivors was 58 months (range, 32-93 months). Fifty-three of 69 patients (77%) remained alive, and 16 of 69 patients (23%) died. Long-term DFS was as follows: 26 of 27 patients had Stage I HB, 3 of 3 patients had Stage II HB, 19 of 25 patients had Stage III HB, and 5 of 14 patients had Stage IV. A complete resection of the primary tumor was achieved in 54 of 63 patients (86%). Six children (8%) had no surgical treatment. Twenty-two tumors were resected primarily, and 41 children underwent surgery after initial chemotherapy. Two children underwent liver transplantation. There was no perioperative death. Forty-eight children received primary chemotherapy with CDDP/IFO/DOXO. Forty-one of 48 children achieved partial remission after CDDP/IFO/DOXO. Eighteen children with advanced or recurrent HB underwent VP16/CARBO chemotherapy, with a response achieved by 12 children. The relevant pretreatment prognostic factors were growth pattern of the liver tumor (P = 0.0135), vascular tumor invasion (P = 0.0039), occurrence of distant metastases (P = 0.0001), initial alpha-fetoprotein level (P = 0.0034), and surgical radicality (P < 0.0001). CONCLUSIONS The current results underline the necessity of preoperative chemotherapy in all children with HB. Complete tumor resection is one of the main prognostic factors.
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Affiliation(s)
- Jörg Fuchs
- Department of Pediatric Surgery, University of Tuebingen, Tuebingen, Germany.
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Charco R, Hidalgo E, Lázaro JL, Vargas V, Castells L, Murio E, Bilbao I, Margarit C. Outcome of cirrhotic patients with incidental hepatocellular carcinoma undergoing liver transplantation. Transplant Proc 2002; 34:299-300. [PMID: 11959294 DOI: 10.1016/s0041-1345(01)02771-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- R Charco
- Liver Transplant Unit, Hospital General Universitario Vall d'Hebron, Barcelona, Spain
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