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Sandella R, Pillai A. A history of transplant oncology-The story of Steve Jobs. Liver Transpl 2025; 31:545-547. [PMID: 39621057 DOI: 10.1097/lvt.0000000000000547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/19/2024] [Indexed: 01/18/2025]
Affiliation(s)
- Rahul Sandella
- Department of Internal Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Anjana Pillai
- Department of Gastroenterology, Hepatology & Nutrition, University of Chicago Medicine, Chicago, Illinois, USA
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Martinino A, Bucaro A, Cardella F, Wazir I, Frongillo F, Ardito F, Giovinazzo F. Liver transplantation vs liver resection in HCC: promoting extensive collaborative research through a survival meta-analysis of meta-analyses. Front Oncol 2024; 14:1366607. [PMID: 38567152 PMCID: PMC10986178 DOI: 10.3389/fonc.2024.1366607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 02/13/2024] [Indexed: 04/04/2024] Open
Abstract
Background HCC is a major global health concern, necessitating effective treatment strategies. This study conducts a meta-analysis of meta-analyses comparing liver resection (LR) and liver transplantation (LT) for HCC. Methods The systematic review included meta-analyses comparing liver resection vs. liver transplantation in HCC, following PRISMA guidelines. Primary outcomes included 5-year overall survival (OS) and disease-free survival (DFS). AMSTAR-2 assessed study quality. Citation matrix and hierarchical clustering validated the consistency of the included studies. Results A search identified 10 meta-analyses for inclusion. The median Pearson correlation coefficient for citations was 0.59 (IQR 0.41-0.65). LT showed better 5-year survival and disease-free survival in all HCC (OR): 0.79; 95% CI: 0.67-0.93, I^2:57% and OR: 0.44; 95% CI: 0.25-0.75, I^2:96%). Five-year survival in early HCC and ITT was 0.63 (95% CI: 0.50-0.78, I^2:0%) and 0.60 (95% CI: 0.39-0.92, I^2:0%). Salvage LT vs. Primary LT did not differ between 5-year survival and disease-free survival (OR: 0.62; 95% CI: 0.33-1.15, I^2:0% and 0.93; 95% CI: 0.82-1.04, I^2:0%). Conclusion Overall, the study underscores the superior survival outcomes associated with LT over LR in HCC treatment, supported by comprehensive meta-analysis and clustering analysis. There was no difference in survival or recurrence rate between salvage LT and primary LT. Therefore, considering the organ shortage, HCC can be resected and transplanted in case of recurrence.
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Affiliation(s)
| | - Angela Bucaro
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, Naples, Italy
| | - Ishaan Wazir
- Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Ardito
- Hepatobilairy and General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Ricker AB, Baker EH, Strand MS, Kalabin A, Butano V, Wells A, Phillips M, Wang H, McKillop I, Iannitti G, Casingal J, Martinie JB, Vrochides D, Iannitti DA. Surgical microwave ablation for the treatment of hepatocellular carcinoma in 791 operations. HPB (Oxford) 2024; 26:379-388. [PMID: 38102029 DOI: 10.1016/j.hpb.2023.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/03/2023] [Accepted: 11/17/2023] [Indexed: 12/17/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and often arises in the setting of cirrhosis. The present series reviews outcomes following 791 operations. METHODS Retrospective review surgical MWA for HCC from March 2007 through December 2022 at a high-volume institution was performed using a prospective database. Primary outcome was overall survival. RESULTS A total of 791 operations in 623 patients and 1156 HCC tumors were treated with surgical MWA. Median tumor size was 2 cm (range 0.25-10 cm) with an average of 1 tumor ablated per operation (range 1-7 tumors). Nearly 90 % of patients had cirrhosis with a median MELD score of 8 (IQR = 6-11). Mortality within 30 days occurred in 13 patients (1.6 %). Per tumor, the rate of incomplete ablation was 2.25 % and local recurrence was 2.95 %. Previous ablation and tumor size were risk factors for recurrence. One-year overall survival was 82.0 % with a median overall survival of 36.5 months (95 % CI 15.7-93.7) and median disease-free survival of 15.9 months (range 5.7-37.3 months). CONCLUSION Surgical MWA offers a low-morbidity approach for treatment of HCC, affording low rates of incomplete ablation and local recurrence.
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Affiliation(s)
- Ansley B Ricker
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Erin H Baker
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Matthew S Strand
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Aleksandr Kalabin
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Vincent Butano
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Alexandra Wells
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Michael Phillips
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Huaping Wang
- Carolinas Center for Surgical Outcomes Science, Atrium Health, Charlotte, NC, USA
| | - Iain McKillop
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Giuliana Iannitti
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Joel Casingal
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - John B Martinie
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - Dionisios Vrochides
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA
| | - David A Iannitti
- Division of HPB Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.
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Drefs M, Schoenberg MB, Börner N, Koliogiannis D, Koch DT, Schirren MJ, Andrassy J, Bazhin AV, Werner J, Guba MO. Changes of long-term survival of resection and liver transplantation in hepatocellular carcinoma throughout the years: A meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107952. [PMID: 38237275 DOI: 10.1016/j.ejso.2024.107952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/21/2023] [Accepted: 01/03/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND Hepatocellular Carcinoma (HCC) still is one of the most detrimental malignant diseases in the world. As two curative surgical therapies exist, the discussion whether to opt for liver resection (LR) or transplantation (LT) is ongoing, especially as novel techniques to improve outcome have emerged for both. The aim of the study was to investigate how the utilization and outcome of the respective modalities changed through time. METHODS We searched Medline and PubMed for relevant publications comparing LT and LR in HCC patients during the time period from 1990 to 2022, prior to March 31, 2023. A total of 63 studies involving 19,804 patients - of whom 8178 patients received a liver graft and 11,626 underwent partial hepatectomy - were included in this meta-analysis. RESULTS LT is associated with significantly better 5-year overall survival (OS) (64.83%) and recurrence-free survival (RFS) (70.20%) than LR (OS: 50.83%, OR: 1.79, p < 0.001; RFS: 34.46%, OR: 5.32, p < 0.001). However, these differences are not as evident in short-term intervals. Older cohorts showed comparable disparities between the outcome of the respective modalities, as did newer cohorts after 2005. This might be due to the similar improvement in survival rates that were observed for both, LT (15-23%) and LR (12-20%) during the last 30 years. CONCLUSION LT still outperforms LR in the therapy of HCC in terms of long-term survival rates. Yet, LR outcome has remarkably improved which is of major importance in reference to the well-known limitations that occur in LT.
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Affiliation(s)
- Moritz Drefs
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany.
| | - Markus B Schoenberg
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Faculty of Medicine, LMU Munich, Germany; Medical Centers Gollierplatz and Nymphenburg, Munich, Germany
| | - Nikolaus Börner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Dionysios Koliogiannis
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Dominik T Koch
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Malte J Schirren
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Joachim Andrassy
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Alexandr V Bazhin
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Faculty of Medicine, LMU Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Markus O Guba
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Transplantation Center Munich, LMU University Hospital, LMU Munich, Germany
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Schwenk L, Rauchfuß F, Ali-Deeb A, Dondorf F, Rohland O, Ardelt M, Settmacher U. [Individualized curative treatment for malignant diseases through liver transplantation]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:122-128. [PMID: 37847311 DOI: 10.1007/s00104-023-01973-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/22/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions. OBJECTIVE This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies. RESULTS AND CONCLUSION Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.
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Affiliation(s)
- Laura Schwenk
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland.
| | - Falk Rauchfuß
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Aladdin Ali-Deeb
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Felix Dondorf
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Oliver Rohland
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Michael Ardelt
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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Wicks JS, Dale BS, Ruffolo L, Pack LJ, Dunne R, Laryea MA, Hernandez-Alejandro R, Sharma AK. Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation. J Clin Med 2023; 12:5006. [PMID: 37568408 PMCID: PMC10419984 DOI: 10.3390/jcm12155006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/20/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.
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Affiliation(s)
- Jeffrey S. Wicks
- Department of Biology, University of Rochester, Rochester, NY 14642, USA;
| | - Benjamin S. Dale
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Luis Ruffolo
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Ludia J. Pack
- Department of Genetics, University of Rochester, Rochester, NY 14642, USA;
| | - Richard Dunne
- Division of Hematology/Oncology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | - Marie A. Laryea
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | | | - Ashwani Kumar Sharma
- Division of Interventional Radiology, Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA
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Claasen MP, Ivanics T, Beumer BR, de Wilde RF, Polak WG, Sapisochin G, IJzermans JN. An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma ✰. JHEP Rep 2023; 5:100745. [PMID: 37234277 PMCID: PMC10206495 DOI: 10.1016/j.jhepr.2023.100745] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 02/14/2023] [Accepted: 03/15/2023] [Indexed: 05/27/2023] Open
Abstract
Background & Aims Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres. Methods A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents' contemporary decision-making process, a hypothetical case study with different tumour size and number combinations was embedded. Results Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise. Conclusions Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA. Impact and implications Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeon vs. oncologist vs. hepatologist/gastroenterologist), highlighting the urgent need for a standardisation of therapeutic strategies for patients with cHCC-CCA.
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Affiliation(s)
- Marco P.A.W. Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, MI, USA
- Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Berend R. Beumer
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Roeland F. de Wilde
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Wojciech G. Polak
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Jan N.M. IJzermans
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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Menon K, Vijayashanker A, Murphy J, Line PD, Isaac J, Adair A, Prasad R, Thorburn D. Liver transplantation for isolated unresectable colorectal liver metastases - Protocol for a service evaluation in the United Kingdom - UKCoMET study. HPB (Oxford) 2023; 25:684-692. [PMID: 36948901 DOI: 10.1016/j.hpb.2023.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/13/2023] [Accepted: 02/13/2023] [Indexed: 03/24/2023]
Abstract
BACKGROUND Liver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation. METHODS Opinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified. RESULTS This paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described. CONCLUSION This service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom.
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Affiliation(s)
- Krishna Menon
- Institute of Liver Studies, King's College Hospital, London, UK; Digestive Diseases and Surgery Institute, Cleveland Clinic London, UK.
| | | | - Jamie Murphy
- Department of Surgery and Cancer, Imperial College London, UK; Digestive Diseases and Surgery Institute, Cleveland Clinic London, UK
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - John Isaac
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Anya Adair
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, UK
| | - Raj Prasad
- Liver Transplantation and HPB Surgery, Leeds Teaching Hospitals, Leeds, UK
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre and UCL Institute for Liver & Digestive Health, Royal Free Hospital, London, UK
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10
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Luo YZ, Zhu H. Immunotherapy for advanced or recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:405-424. [PMID: 37009314 PMCID: PMC10052663 DOI: 10.4251/wjgo.v15.i3.405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 02/11/2023] [Accepted: 02/28/2023] [Indexed: 03/14/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality, and is prone to intra- and extrahepatic metastasis due to the anatomical and functional characteristics of the liver. Due to the complexity and high relapse rate associated with radical surgery or radiofrequency ablation, immune checkpoint inhibitors (ICIs) are increasingly being used to treat HCC. Several immunotherapeutic agents, along with their combinations, have been clinically approved to treat advanced or recurrent HCC. This review discusses the leading ICIs in practice and those currently undergoing randomized phase 1–3 trials as monotherapy or combination therapy. Furthermore, we summarize the rapidly developing alternative strategies such as chimeric antigen receptor-engineered T cell therapy and tumor vaccines. Combination therapy is a promising potential treatment option. These immunotherapies are also summarized in this review, which provides insights into the advantages, limitations, and novel angles for future research in establishing viable and alternative therapies against HCC.
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Affiliation(s)
- Ying-Zhe Luo
- Department of Medical Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Hong Zhu
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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11
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Jonas E, Bernon M, Robertson B, Kassianides C, Keli E, Asare KO, Alatise IO, Okello M, Blondel NO, Mulehane KO, Abubeker ZA, Nogoud AA, Nashidengo PR, Chihaka O, Tzeuton C, Dusheiko G, Sonderup M, Spearman CW. Treatment of hepatocellular carcinoma in sub-Saharan Africa: challenges and solutions. Lancet Gastroenterol Hepatol 2022; 7:1049-1060. [PMID: 35810767 DOI: 10.1016/s2468-1253(22)00042-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 06/15/2023]
Abstract
Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.
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Affiliation(s)
- Eduard Jonas
- Department of Surgery, University of Cape Town, Cape Town, South Africa.
| | - Marc Bernon
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Barbara Robertson
- Division of Radiation Oncology, Department of Radiation Medicine, University of Cape Town, Cape Town, South Africa
| | - Chris Kassianides
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Elie Keli
- Department of General and Digestive Surgery, Hôpital Militaire d'Abidjan, Abidjan, Côte d'Ivoire
| | - Kwaku Offei Asare
- Department of Surgery, Korle Bu Teaching Hospital and the University of Ghana Medical School, Accra, Ghana
| | - Isaac Olusegun Alatise
- Department of Surgery, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, Nigeria
| | - Michael Okello
- Department of Surgery, Uganda Martyrs Hospital Lubaga, Kampala, Uganda
| | - Nana Oumarou Blondel
- Centre Hospitalier d'Essos and Department of Surgery, University of Yaoundé, Yaoundé, Cameroon
| | | | - Zeki Abdurahman Abubeker
- Department of Surgery, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Pueya Rashid Nashidengo
- Department of Surgery, Windhoek Central Hospital, University of Namibia School of Medicine, Windhoek, Namibia
| | - Onesai Chihaka
- Department of Surgery, University of Zimbabwe, Harare, Zimbabwe
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Geoffrey Dusheiko
- Institute of Liver Studies, King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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12
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Kim SJ, Kim JM. Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review. Clin Mol Hepatol 2022; 28:739-753. [PMID: 35468711 PMCID: PMC9597239 DOI: 10.3350/cmh.2022.0060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/05/2022] [Accepted: 04/15/2022] [Indexed: 01/05/2023] Open
Abstract
Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.
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Affiliation(s)
- Sang Jin Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
- Division of Hepatobiliopancreas and Transplant Surgery, Korea University Ansan Hospital, Republic of Korea, Ansan, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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13
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Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
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14
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Radiofrequency ablation versus trans-arterial chemoembolization in patients with HCC awaiting liver transplant: an analysis of the Scientific Registry of Transplant Recipients. J Vasc Interv Radiol 2022; 33:1222-1229.e1. [PMID: 35777619 DOI: 10.1016/j.jvir.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 04/21/2022] [Accepted: 06/21/2022] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To evaluate differences in waitlist mortality/dropout for liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency ablation (RFA) versus trans-arterial chemoembolization (TACE). MATERIAL AND METHODS From 2004-2013, 11,824 patients in the Scientific Registry of Transplant Recipients (SRTR) with HCC who underwent RFA or TACE. Patients were followed until December 31, 2019 or 5 years, whichever came first and stratified by Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality/dropout were performed with adjusted hazard ratios (asHR, reference group RFA). Regression models were adjusted for age, race, sex, calculated Model for End Stage Liver Disease (cMELD) score, tumor size, and number. RESULTS There was no difference in waitlist mortality/dropout for patients outside Milan criteria (N = 1,226) between TACE (19.2%) compared to RFA (19.0%) (asHR 0.91; 95% CI 0.79-1.03). There was also no difference for patients inside Milan criteria (N = 10,598) in waitlist mortality/dropout (TACE 13.4% vs. RFA 12.9%) (asHR 1.29; 95% CI 0.79-2.09). Subgroup analysis within Milan criteria demonstrated no evidence of difference in TACE compared to RFA in patients with single tumor ≤3 cm (asHR 0.92; 95% CI 0.77-1.10), single tumor > 3 cm (asHR 1.03; 95% CI 0.79-1.34), or with > 1 tumor (asHR 0.89; 95% CI 0.72-1.09). CONCLUSION Using national registry data, no difference was found in waitlist mortality/dropout for transplant candidates with HCC who received TACE vs. RFA.
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15
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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16
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Biolato M, Galasso T, Marrone G, Miele L, Grieco A. Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation. Cancers (Basel) 2021; 13:6337. [PMID: 34944957 PMCID: PMC8699392 DOI: 10.3390/cancers13246337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022] Open
Abstract
In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60-70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to "extended" downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
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Affiliation(s)
- Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Tiziano Galasso
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Luca Miele
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
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17
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Frankul L, Frenette C. Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy. J Clin Transl Hepatol 2021; 9:220-226. [PMID: 34007804 PMCID: PMC8111105 DOI: 10.14218/jcth.2020.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 10/04/2020] [Accepted: 03/04/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
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Affiliation(s)
| | - Catherine Frenette
- Correspondence to: Catherine Frenette, Scripps Center for Organ Transplant, Scripps Clinic/Green Hospital, 10666 N. Torrey Pines Rd N200, La Jolla, CA 92037, USA. ORCID: https://orcid.org/0000-0002-2245-8173 Tel: +1-858-554-4310, Fax: +1-858-554-3009, E-mail:
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18
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Gabr A, Kulik L, Mouli S, Riaz A, Ali R, Desai K, Mora RA, Ganger D, Maddur H, Flamm S, Boike J, Moore C, Thornburg B, Alasadi A, Baker T, Borja-Cacho D, Katariya N, Ladner DP, Caicedo JC, Lewandowski RJ, Salem R. Liver Transplantation Following Yttrium-90 Radioembolization: 15-Year Experience in 207-Patient Cohort. Hepatology 2021; 73:998-1010. [PMID: 32416631 DOI: 10.1002/hep.31318] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/31/2020] [Accepted: 05/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P < 0.0001). For patients with UNOS T2 treated during the study period, 5.2% dropped out because of disease progression. CONCLUSIONS Y90 is an effective treatment for HCC in the setting of bridging/downstaging to LT. Patients who achieved extensive or complete necrosis had better RFS, supporting the practice of neoadjuvant treatment before LT.
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Affiliation(s)
- Ahmed Gabr
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Laura Kulik
- Department of MedicineDivision of HepatologyNorthwestern UniversityChicagoIL
| | - Samdeep Mouli
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Ahsun Riaz
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Rehan Ali
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Kush Desai
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Ronald A Mora
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Daniel Ganger
- Department of MedicineDivision of HepatologyNorthwestern UniversityChicagoIL
| | - Haripriya Maddur
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Steven Flamm
- Department of MedicineDivision of HepatologyNorthwestern UniversityChicagoIL
| | - Justin Boike
- Department of MedicineDivision of HepatologyNorthwestern UniversityChicagoIL
| | - Christopher Moore
- Department of MedicineDivision of HepatologyNorthwestern UniversityChicagoIL
| | - Bartley Thornburg
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Ali Alasadi
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL
| | - Talia Baker
- Department of SurgeryDivision of TransplantationUniversity of ChicagoChicagoIL
| | - Daniel Borja-Cacho
- Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
| | - Nitin Katariya
- Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
| | - Daniela P Ladner
- Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
| | - Juan Carlos Caicedo
- Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
| | - Robert J Lewandowski
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL.,Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
| | - Riad Salem
- Department of RadiologySection of Interventional RadiologyNorthwestern Memorial HospitalRobert H. Lurie Comprehensive Cancer CenterChicagoIL.,Department of SurgeryDivision of TransplantationComprehensive Transplant CenterNorthwestern UniversityChicagoIL
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19
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Heimbach JK. Evolution of Liver Transplant Selection Criteria and U.S. Allocation Policy for Patients with Hepatocellular Carcinoma. Semin Liver Dis 2020; 40:358-364. [PMID: 32942324 DOI: 10.1055/s-0040-1709492] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Liver transplantation (LT) is an optimal treatment option for early-stage unresectable hepatocellular carcinoma (HCC) in patients with cirrhosis as it provides a treatment for underlying liver disease as well as a decreased incidence of recurrent cancer compared with alternative treatment strategies. A primary barrier to LT for HCC is the critical shortage of available liver allografts. The system of prioritization and access to deceased donor transplantation for patient with HCC in the United States has continued to evolve, while variable approaches including no additional priority, are in use around the world. While the Milan criteria remain the most well-established pretransplantation selection criteria, multiple other algorithms which expand beyond Milan have been proposed. The current review focuses on liver allocation for HCC as well as the principles and varied models available for pretransplant patient selection.
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Affiliation(s)
- Julie K Heimbach
- Department of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, Minnesota
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20
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Yohanathan L, Heimbach JK. The Impact of Allocation Changes on Patients with Hepatocellular Carcinoma. Clin Liver Dis 2020; 24:657-663. [PMID: 33012451 DOI: 10.1016/j.cld.2020.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Since the establishment of the Milan criteria, liver transplantation (LT) has been identified as an optimal therapy for selected patients with early stage, unresectable hepatocellular carcinoma (HCC) complicating cirrhosis, although a major limitation is the critical shortage of available deceased donor liver allografts. This review focuses on the evolution of liver allocation for HCC in the United States and what the most recent revisions to the allocation system mean for patients with HCC.
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Affiliation(s)
- Lavanya Yohanathan
- Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Julie K Heimbach
- Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
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21
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Dosimetric analysis and comparison of volumetric-modulated arc therapy versus intensity-modulated radiation therapy for liver carcinoma. JOURNAL OF RADIOTHERAPY IN PRACTICE 2020. [DOI: 10.1017/s1460396920000916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractAim:This study dosimetrically compared volumetric-modulated arc therapy (VMAT) to intensity-modulated arc therapy (IMRT) for patients with liver carcinoma.Materials and methods:Ten patients with liver carcinoma previously treated with IMRT or VMAT were retrospectively selected for this study. Each patient received a total dose of 54 Gy in 1·8 Gy fractions. Dosimetric evaluations for each patient were performed using the dose–volume histograms (DVHs) for planning target volumes (PTVs) and organs at risk (OAR). All dosimetric parameters were statistically analysed using mean values, standard deviations and p-values for determining the significance. The conformality index (CI) and homogeneity index (HI) were calculated and compared. For efficiency evaluation, monitor units (MUs) and beam on times (BOT) were recorded.Results:Compared to IMRT, VMAT plans showed significant differences in the heterogeneity with p < 0·01 and insignificant differences in both conformality and normal tissue sparing. VMAT required marginally fewer mean MU and shorter BOT when compared to IMRT with insignificant differences.Conclusions:For radiation therapy treatment of liver carcinoma, IMRT and VMAT can achieve similar PTV coverage and normal tissue sparing. Treatment time is only marginally shorter with VMAT versus IMRT with insignificant differences.
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Malla RR, Kumari S, Kgk D, Momin S, Nagaraju GP. Nanotheranostics: Their role in hepatocellular carcinoma. Crit Rev Oncol Hematol 2020; 151:102968. [DOI: 10.1016/j.critrevonc.2020.102968] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/24/2020] [Accepted: 04/15/2020] [Indexed: 12/14/2022] Open
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Cortese S, Morales J, Martín L, Kayser S, Colón A, Ramón E, Tellado JM. Resección hepática con trombectomía en el tratamiento del carcinoma hepatocelular con invasión vascular macroscópica. Cir Esp 2020; 98:9-17. [DOI: 10.1016/j.ciresp.2019.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 05/19/2019] [Accepted: 06/27/2019] [Indexed: 01/27/2023]
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Chagas AL, Felga GE, Diniz MA, Silva RF, Mattos AA, Silva RC, Boin IF, Garcia JH, Lima AS, Coelho JC, Bittencourt PL, Alves VA, D’Albuquerque LA, Carrilho FJ. Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival. Eur J Gastroenterol Hepatol 2019; 31:1148-1156. [PMID: 31247632 PMCID: PMC6687037 DOI: 10.1097/meg.0000000000001448] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 04/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.
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Affiliation(s)
- Aline L. Chagas
- Department of Gastroenterology
- São Paulo Clinicas Liver Cancer Group
| | - Guilherme E.G. Felga
- Liver Transplantation Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | | | - Renato F. Silva
- Serviço de Gastroenterologia e Unidade de Transplante de Fígado, Hospital de Base – FUNFARME, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto
| | - Angelo A. Mattos
- Department of Gastroenterology, Fundação Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre
| | - Rita C.M.A. Silva
- Serviço de Gastroenterologia e Unidade de Transplante de Fígado, Hospital de Base – FUNFARME, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto
| | - Ilka F.S.F. Boin
- Unit of Liver Transplantation, State University of Campinas, Campinas
| | - José H.P. Garcia
- Ceará Unit of Liver Transplantation, Department of Surgery and Liver Transplantation, Federal University of Ceará, Fortaleza
| | - Agnaldo S. Lima
- School of Medicine, Federal University of Minas Gerais, Belo Horizonte
| | | | | | - Venâncio A.F. Alves
- Department of Pathology, University of São Paulo School of Medicine
- São Paulo Clinicas Liver Cancer Group
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Composite criteria using clinical and FDG PET/CT factors for predicting recurrence of hepatocellular carcinoma after living donor liver transplantation. Eur Radiol 2019; 29:6009-6017. [DOI: 10.1007/s00330-019-06239-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/10/2019] [Accepted: 04/12/2019] [Indexed: 12/18/2022]
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Gans JH, Lipman J, Golowa Y, Kinkhabwala M, Kaubisch A. Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in? Semin Nucl Med 2019; 49:170-181. [DOI: 10.1053/j.semnuclmed.2019.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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O'Rourke JM, Shetty S, Shah T, Perera MTPR. Liver transplantation for hepatocellular carcinoma: pushing the boundaries. Transl Gastroenterol Hepatol 2019; 4:1. [PMID: 30854488 DOI: 10.21037/tgh.2018.12.07] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 12/05/2018] [Indexed: 12/12/2022] Open
Affiliation(s)
| | | | - Tahir Shah
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
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Schoenberg MB, Bucher JN, Vater A, Bazhin AV, Hao J, Guba MO, Angele MK, Werner J, Rentsch M. Resection or Transplant in Early Hepatocellular Carcinoma. DEUTSCHES ARZTEBLATT INTERNATIONAL 2018; 114:519-526. [PMID: 28835324 DOI: 10.3238/arztebl.2017.0519] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 12/07/2016] [Accepted: 05/22/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) has an incidence of 5-10 per 100 000 persons per year in the Western world. In 20% of cases, surgical liver resection (LR) or liver transplantation (LT) can be performed. LT results in longer survival, as it involves resection not only of the tumor, but of pre - cancerous tissue as well. The optimal allocation of donor organs depends on the identification of patients for whom LR is adequate treatment. In this meta-analysis, we compare LT and LR for patients with early HCC and wellcompensated cirrhosis. METHODS A systematic review of the pertinent literature was followed by a subgroup analysis of the studies in which patients with early HCC and wellcompensated cirrhosis were followed up after either LR or LT. Overall survival at 1, 3, and 5 years, as well as morbidity and mortality, were compared in a random effects meta-analysis. RESULTS 54 studies with a total of 13 794 patients were included. Among patients with early HCC, the overall survival after LT became higher than the overall survival after LR 5 years after surgery (66.67% versus 60.35%, odds ratio 0.60 [0.45; 0.78], p <0.001); there was no significant difference 1 year or 3 years after surgery. Nor was there any significant difference in morbidity or mortality between the two types of treatment in this subgroup. These findings contrast with the results obtained in all of the studies, which documented significantly better survival 3 years after LT. CONCLUSION Three years after surgery, the survival rates and complication rates of patients with early HCC treated with either LR or LT are comparable. Resection should therefore be the preferred form of treatment if the prerequisites for it are met. In case of recurrent tumor, these patients can still be evaluated for liver transplantation. This strategy could improve the allocation of donor organs.
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Affiliation(s)
- Markus B Schoenberg
- Markus B. Schoenberg and Julian N. Bucher shared first authorship; Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Campus Großhadern; Munich Transplant Center, University Hospital of Munich, Campus Großhadern; Liver Center Munich, University Hospital of Munich, Campus Großhadern
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Kotewall CN, Cheung TT. Optimizing hepatectomy for hepatocellular carcinoma in Asia-patient selection and special considerations. Transl Gastroenterol Hepatol 2018; 3:75. [PMID: 30505962 DOI: 10.21037/tgh.2018.09.09] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 09/05/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common affliction in Asia. The treatment of HCC depends on the tumor status as well as the underlying liver function. Resection is the cornerstone of surgical management of HCC. For those unfit to undergo resection, local ablative therapy is a viable alternative. For patients with multiple small unresectable HCCs, liver transplantation offers another option, having the simultaneous benefit of removing the cancer in addition to replacing the pre-malignant and cirrhotic liver together. However, the paucity of liver grafts limits the applicability of this operation. In assessing for the appropriate treatment, the traditional TNM staging is not widely applied to HCC. Conventionally, doctors in the West have relied on the Barcelona staging system. Asian surgeons, on the other hand, have long adopted a more aggressive approach for their patients. Borne out of the need for a system which better suited Asian patients, the Hong Kong guidelines have been established. For the surgical resection of HCC, considerations must take into account issues regarding the tumor, the underlying liver and the patient. For the tumor, the size, the presence vascular invasion and presence of extra-hepatic metastasis will determine operability. Another important issue is the liver function and, by extension, the estimated residual liver volume after resection. Thirdly, patient factors i.e., fitness to undergo general anesthesia must be properly assessed. With improved surgical technique and better patient selection, peri-operative morbidity and long-term survival results after operation have improved drastically over the past decades.
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Affiliation(s)
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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Cook D, Achanta S, Hoek JB, Ogunnaike BA, Vadigepalli R. Cellular network modeling and single cell gene expression analysis reveals novel hepatic stellate cell phenotypes controlling liver regeneration dynamics. BMC SYSTEMS BIOLOGY 2018; 12:86. [PMID: 30285726 PMCID: PMC6171157 DOI: 10.1186/s12918-018-0605-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 08/21/2018] [Indexed: 12/26/2022]
Abstract
Background Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate cell (HSC) functional phenotypes to the tightly regulated physiological response of liver regeneration. Results We develop a mathematical model describing contributions of HSC functional phenotype populations to liver regeneration and test model predictions through isolation and transcriptional characterization of single HSCs. We identify and characterize four HSC transcriptional states contributing to liver regeneration, two of which are described for the first time in this work. We show that HSC state populations change in vivo in response to acute challenges (in this case, 70% partial hepatectomy) and chronic challenges (chronic ethanol consumption). Our results indicate that HSCs influence the dynamics of liver regeneration through steady-state tissue preconditioning prior to an acute insult and through dynamic control of cell state balances. Furthermore, our modeling approach provides a framework to understand how balances among cell states influence tissue dynamics. Conclusions Taken together, our combined modeling and experimental studies reveal novel HSC transcriptional states and indicate that baseline differences in HSC phenotypes as well as a dynamic balance of transitions between these phenotypes control liver regeneration responses. Electronic supplementary material The online version of this article (10.1186/s12918-018-0605-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Daniel Cook
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.,Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Sirisha Achanta
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Jan B Hoek
- Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Babatunde A Ogunnaike
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA
| | - Rajanikanth Vadigepalli
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. .,Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
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Cho SH, Pak K, Jeong DC, Han M, Oh S, Kim YH. The AP2M1 gene expression is a promising biomarker for predicting survival of patients with hepatocellular carcinoma. J Cell Biochem 2018; 120:4140-4146. [DOI: 10.1002/jcb.27699] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 08/27/2018] [Indexed: 12/31/2022]
Affiliation(s)
- Sung Hwan Cho
- Department of Surgery Pusan National University Yangsan Hospital Yangsan Korea
| | - Kyoungjune Pak
- Department of Nuclear Medicine and Biomedical Research Institute Pusan National University Hospital Busan Korea
| | | | - Myoung‐Eun Han
- Department of Anatomy School of medicine, Pusan National University Yangsan Korea
| | - Sae‐Ock Oh
- Department of Anatomy School of medicine, Pusan National University Yangsan Korea
| | - Yun Hak Kim
- Department of Anatomy School of medicine, Pusan National University Yangsan Korea
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Preoperative nutrition and postoperative liver function: a correlation study of pediatric living donor liver transplantation. FRONTIERS OF NURSING 2018. [DOI: 10.2478/fon-2018-0020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Objective
There is little information focusing on the nutritional issue of pediatric recipients before they receive living donor liver transplantation. This study illustrates the relationship between nutritional status and graft liver function and provides a reference regarding nutritional interventions in future studies.
Methods
We prospectively collected data from 30 pediatric living donor liver transplant recipients from January 1, 2016, to June 30, 2016. The information included demographic data, preoperative nutritional assessment, and postoperative laboratory examinations. The nutritional assessment included the serum concentration of vitamin D, bone density, trace element, and weight Z value. The laboratory examinations included white blood cell count, neutrophil percentage, hemoglobin, blood platelet, total protein, albumin, total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase, creatinine, bile acid, blood glucose (Glu), prothrombin time, international normalized ratio, tacrolimus concentration, and graft-to-recipient weight ratio (GRWR). The data were collected on Days 1, 2, 3, 4, 5, 6, 7, 14, 30, and 60 after liver transplantation.
Results
The recipients consisted of 15 (50%) males and 15 (50%) females. The median age was 7 months (4–48 months). The mean height and weight were 69.07±9.98 cm and 8.09±2.63 kg, respectively. According to the univariate analysis, the gender, diagnosis, blood type, and GRWR did not significantly impact the liver function after the operation. The posttransplantation AST levels and Glu showed significant differences in terms of the nutritional status, with P<0.05. The multivariate correlation analysis showed that the serum concentrations of vitamin D and AST were midrange positively correlated, with P<0.05.
Conclusions
The nutritional status of patients with biliary atresia is relatively poor. There is a definite midrange positive correlation between nutrition and graft liver function that might play a relatively important role in the recovery of the graft.
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Saberi B, Garonzik-Wang J, Ma M, Ajayi T, Kim A, Luu H, Jakhete N, Pustavoitau A, Anders RA, Georgiades C, Kamel I, Ottmann S, Philosophe B, Cameron AM, Gurakar A. Accuracy of Milan, University of California San Francisco, and Up-To-7 Criteria in Predicting Tumor Recurrence Following Deceased-Donor Liver Transplant in Patients With Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2018; 18:463-469. [PMID: 30084757 DOI: 10.6002/ect.2017.0288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES We aimed to investigate the accuracy of the Milan, University of California San Francisco, and Up-to-7 criteria in predicting tumor recurrence after liver transplant for hepatocellular carcinoma. MATERIALS AND METHODS For this study, 165 patients with deceased-donor liver transplant for hepatocellular carcinoma were evaluated. The Milan, University of California San Francisco, and Up-to-7 criteria were calculated based on explant pathology. RESULTS Tumor recurrence rate after liver transplant was 14.6%. Of 165 patients, 115 (70%) were within Milan, 131 (79%) were within University of California San Francisco, and 135 (82%) were within Up-to-7 criteria. The odds ratio of tumor recurrence in patients outside versus within criteria for Milan, University of California San Francisco, and Up-to-7 was 3.6 (95% confidence interval, 1.5-9.1; P = .005), 7.5 (95% confidence interval, 2.5-19.3; P < .001), and 7.5 (95% confidence interval, 2.9-19.6; P < .001) times higher, respectively. The sensitivity of being outside of Milan in predicting tumor recurrence was comparable to University of California San Francisco and Up-to-7 criteria (56.5%, 56.5%, and 52.2%, respectively). Specificity was highest in Up-to-7 (87.3%) versus 85.2% for University of California San Francisco and 73.9% for Milan criteria. The area under the curve for Milan, University of California San Francisco, and Up-to-7 criteria was 0.63, 0.65, and 0.63. CONCLUSIONS Application of standard criteria has significantly improved prediction of hepatocellular carcinoma recurrence. However, these criteria are inadequate, supporting the importance of other factors, including tumor biology. Research is ongoing in discovering novel biomarkers as predictors of tumor recurrence.
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Affiliation(s)
- Behnam Saberi
- From the Division of Gastroenterology and Hepatology-Transplant Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Commander SJ, Shaw B, Washburn L, Yoeli D, Rana A, Goss JA. A long-term experience with expansion of Milan criteria for liver transplant recipients. Clin Transplant 2018; 32:e13254. [DOI: 10.1111/ctr.13254] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2018] [Indexed: 12/16/2022]
Affiliation(s)
- Sarah Jane Commander
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Brian Shaw
- Division of Abdominal Transplantation; University of California-San Francisco; San Francisco CA USA
| | - Laura Washburn
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Dor Yoeli
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Abbas Rana
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - John A. Goss
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
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Staudacher C, Chiappa A, Biella F, Audisio RA, Bertani E, Zbar AP. Validation of the Modified Tnm-Izumi Classification for Hepatocellular Carcinoma. TUMORI JOURNAL 2018; 86:8-11. [PMID: 10778759 DOI: 10.1177/030089160008600102] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
AIMS AND BACKGROUND The clinical value of the UICC TNM classification and the Izumi TNM modification regarding prognosis after hepatic resection was evaluated. METHODS Between January 1993 and December 1998, survival and disease-free survival were analyzed in 53 cirrhotic patients (40 males, 13 females; mean age, 65 years; range, 43-81) who underwent hepatic resection for HCC. RESULTS The 1-, 3-, and 5-year overall survivals were: 89%, 54%, and 50%, with disease-free survivals of 70%, 38%, and 28%, respectively. The difference between stages 1 and 2 or stages 3 and 4A using the UICC TNM classification was not significant with respect to survival or disease-free survival. Conversely, the Izumi TNM modification showed a significant difference between each stage with respect to survival and disease-free survival. In a multivariate analysis the lack of micro/macro vascular invasion was predictive of long-term outcome. CONCLUSIONS Our results show that the UICC TNM classification for hepatocellular carcinoma is inadequate. The Izumi modified TNM staging system is superior in assessing prognosis for surgical HCC patients.
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Affiliation(s)
- C Staudacher
- Department of Emergency Surgery, Surgical Oncology, University of Milan, School of Medicine, San Raffaele Scientific Institute, Italy
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Liver transplantation for hepatocellular carcinoma within the Milan criteria versus the University of California San Francisco criteria: a comparative study. Eur J Gastroenterol Hepatol 2018; 30:398-403. [PMID: 29280920 DOI: 10.1097/meg.0000000000001044] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Currently, liver transplantation (LT) for HCC is the only hope for cure from the tumor and from end-stage liver disease (ESLD). The organ pool shortage in deceased donor LT and the donor-related ethical concerns in living-donor LT necessitate the use of rigorous criteria for LT for HCC. In this respect, two main criteria for LT for HCC were implemented with good outcome, namely, the Milan and the University of California San Francisco criteria. Comparison of the outcome of LT for HCC using either of the two criteria has seldom been reported in the literature. PATIENTS AND METHODS Eighty-eight patients underwent LT between August 2003 and end of July 2013 for the presence of pathologically proven pure HCC lesions at our institution. Cases of pediatric LT or liver retransplantation were excluded from this study. Cases with mixed HCC and cholangiocarcinoma were excluded from this study. RESULTS Eighty-eight patients underwent LT between August 2003 and July 2013 for the presence of pathologically proven pure HCC lesions at our institution. The mean follow-up duration was 45±30.9 months. HCC recurrence was related significantly to the presence of vascular invasion and degree of differentiation of HCC lesion (P value of 0.0001 and 0.001, respectively). CONCLUSION Patient and tumor free survival did not differ significantly between patients within Milan or University of California San Francisco criteria or beyond both criteria. Vascular invasion and poor differentiation are still the most influential factors for post-transplant long-term outcomes in HCC patients.
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Wang G, Liu H, Wei Z, Jia H, Liu Y, Liu J. Systematic analysis of the molecular mechanism of microRNA-124 in hepatoblastoma cells. Oncol Lett 2018; 14:7161-7170. [PMID: 29344147 PMCID: PMC5754889 DOI: 10.3892/ol.2017.7131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 08/10/2017] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to identify the molecular mechanisms of microRNA-124 (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained from the Gene Expression Omnibus database, included samples extracted from HepG2 cells transfected with miR-124 duplex (the experimental group) or negative control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection. Differentially expressed genes (DEGs) were screened between the two groups. miR-124 activity was inferred based on the expression of its target genes. The mRNAs targeted by miR-124 were predicted and a miR-124-target mRNA network was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the target genes. The number of DEGs was highest at 72 h. The experimental group had higher miR-124 activity than that of the control group at 4, 8, 16, 24 and 120 h. Small GTPase-mediated signal transduction and Ras protein signal transduction were significant GO terms enriched with syndecan binding protein (SDCBP), Ras homolog family member G (RHOG) and Rho-GDP dissociation inhibitor-α (ARHGDIA). Regulation of actin cytoskeleton, D-glutamine and D-glutamate metabolism, and axon guidance were significant pathways. Axon guidance pathway was associated with neuropilin (NRP1), MET proto-oncogene, receptor tyrosine kinase (MET) and semaphorin 7A, GPI membrane anchor (SEMA7A). Small GTPase-mediated signal transduction, Ras protein signal transduction, regulation of actin cytoskeleton pathway, D-glutamine and D-glutamate metabolism pathway, axon guidance pathway, SDCBP, RHOG, ARHGDIA, NRP1, SEMA7A, and MET may be implicated in the underlying mechanisms of miR-124 overexpression in hepatoblastoma.
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Affiliation(s)
- Guiming Wang
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Hong Liu
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Zhigang Wei
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Hongyan Jia
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Yu Liu
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Jiansheng Liu
- Department of Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
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Najjar M, Agrawal S, Emond JC, Halazun KJ. Pretreatment neutrophil-lymphocyte ratio: useful prognostic biomarker in hepatocellular carcinoma. J Hepatocell Carcinoma 2018; 5:17-28. [PMID: 29404284 PMCID: PMC5779314 DOI: 10.2147/jhc.s86792] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy and the third most common cause of cancer-related deaths. Liver resection (LR) and liver transplantation (LT) are the only curative modalities for HCC. Despite recent advances and the adoption of the Milan and University of California, San Francisco, criteria, HCC recurrence after LR and LT remains a challenge. Several markers and prognostic scores have been proposed to predict tumor aggressiveness and supplement radiological data; among them, neutrophil–lymphocyte ratio (NLR) has recently gained significant interest. An elevated NLR is thought to predispose to HCC recurrence by creating a protumorigenic microenvironment through both relative neutrophilia and lymphocytopenia. In the present review, we attempted to summarize the published work on the role of pretreatment NLR as a prognostic marker for HCC following LR and LT. A total of 13 LT and 18 LR studies were included from 2008 to 2015. Pretransplant NLR was most often predictive of HCC recurrence, recurrence-free survival, and overall survival. NLR was, however, more variably and less clearly associated with worse outcomes following LR.
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Affiliation(s)
- Marc Najjar
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA
| | - Surbhi Agrawal
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA
| | - Jean C Emond
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA
| | - Karim J Halazun
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA.,Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Weill Cornell Medical College, New York, NY, USA
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Kornberg A, Witt U, Schernhammer M, Kornberg J, Ceyhan GO, Mueller K, Friess H, Thrum K. Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma. Sci Rep 2017; 7:14176. [PMID: 29074969 PMCID: PMC5658419 DOI: 10.1038/s41598-017-14430-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 10/10/2017] [Indexed: 02/06/2023] Open
Abstract
The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%; p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non- 18F-FDG-avid and 18F-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25; p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT.
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Affiliation(s)
- Arno Kornberg
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany.
| | - Ulrike Witt
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Martina Schernhammer
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Jennifer Kornberg
- Department of Anaesthesiology, Klinikum Großhadern, LMU, Munich, Germany
| | - Gueralp O Ceyhan
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | | | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Katharina Thrum
- Institute of Pathology, Helios Klinikum Berlin, Berlin, Germany
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Effect of Preoperative Growth Status on Clinical Outcomes After Living-Donor Liver Transplantation in Infants. Transplant Proc 2017; 49:1848-1854. [DOI: 10.1016/j.transproceed.2017.06.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 06/16/2017] [Indexed: 12/27/2022]
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Kornberg A, Schernhammer M, Friess H. 18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:224-234. [PMID: 28936404 PMCID: PMC5606969 DOI: 10.14218/jcth.2017.00014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 05/18/2017] [Accepted: 06/05/2017] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.
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Affiliation(s)
- Arno Kornberg
- *Correspondence to: Arno Kornberg, Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, D-81675 Munich, Germany. Tel: +89-41405087, Fax: +89-41404884, E-mail:
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The Impact of Bridging LRT on Survival in Patients Listed for Liver Transplantation. Cardiovasc Intervent Radiol 2017; 41:112-119. [DOI: 10.1007/s00270-017-1759-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 07/25/2017] [Indexed: 01/29/2023]
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Cho Y, Lee JH, Lee DH, Cho EJ, Yu SJ, Yi NJ, Lee KW, Kim YJ, Yoon JH, Suh KS. Comparison of treatment outcome between living donor liver transplantation and sorafenib for patients with hepatocellular carcinoma beyond the Milan criteria. Oncotarget 2017; 8:47555-47564. [PMID: 28548930 PMCID: PMC5564586 DOI: 10.18632/oncotarget.17733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 04/26/2017] [Indexed: 01/10/2023] Open
Abstract
For patients with advanced hepatocellular carcinoma (HCC), sorafenib is the only systemic treatment recommended by international guidelines. We recently reported that HCC patients with a low MoRAL (model to predict tumor recurrence after LDLT) score (≤ 314.8) have excellent treatment outcomes after living-donor liver transplantation (LDLT), even though they are beyond the Milan criteria. In the present study, we investigated whether LDLT offers a better treatment outcome than sorafenib for patients with HCC beyond the Milan criteria according to the MoRAL score. A retrospective cohort study of 325 consecutive patients who were treated with either LDLT (n = 122) or sorafenib (n = 203) for HCC beyond the Milan criteria from 2005 to 2014 at a tertiary hospital was performed. The primary and secondary endpoints were overall survival (OS) and time-to-progression. When baseline characteristics were balanced using inverse probability weighting, OS was significantly longer in the LDLT group than in the sorafenib group (5-year OS rate, 71.9% vs. 4.9%; HR=0.1; P < 0.001). The LDLT group exhibited a significantly lower risk of tumor progression (5-year recurrence rate, 34.7% vs. 96%; HR=0.14; P < 0.001) than the sorafenib group. The increase in OS with LDLT was predominantly among patients with a low MoRAL score (5-year OS rate, 81.1% vs. 5.8%; HR=0.06; P < 0.001) compared with those with a high MoRAL score (5-year OS rate, 28.3% vs. 4.3%; HR = 0.42; P = 0.047). Patients with a low MoRAL score and without extrahepatic metastasis or hepatic vein invasion might be good candidates for LDLT instead of sorafenib treatment if there is a willing living related donor.
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Affiliation(s)
- Yuri Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Hyeon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Acarlı K. Liver Transplantation for Hepatocellular Carcinoma: "Experience of Memorial Sisli Hospital". J Gastrointest Cancer 2017. [PMID: 28647820 DOI: 10.1007/s12029-017-9966-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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45
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Wu CF, Wu YJ, Liang PC, Wu CH, Peng SF, Chiu HW. Disease-free survival assessment by artificial neural networks for hepatocellular carcinoma patients after radiofrequency ablation. J Formos Med Assoc 2017; 116:765-773. [PMID: 28117199 DOI: 10.1016/j.jfma.2016.12.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 11/13/2016] [Accepted: 12/19/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/PURPOSE Radiofrequency ablation (RFA) provides an effective treatment for patients who exhibit early hepatocellular carcinoma (HCC) stages or are waiting for liver transplantation. It is important to assess patients after RFA. The goal of this study was to build artificial neural network models with HCC-related variables to predict the 1-year and 2-year disease-free survival (DFS) of HCC patients receiving RFA treatments. METHODS This study was a retrospective study that tracked HCC patients who received computer tomography-guided percutaneous RFA between January 2009 and April 2012. The numbers of total patients with 1-year and 2-year DFS were 252 and 179, respectively. A total of 15 HCC clinical variables were collected for the construction of artificial neural network models for DFS prediction. Internal validation and validation conducted using simulated prospective data were performed. RESULTS The results showed that the model with 15 inputs showed better performance compared with the models including only significant features. Parameters for performance assessment of 1-year DFS prediction were as follows: accuracy 85.0% (70.0%), sensitivity 75.0% (63.3%), specificity 87.5% (71.8%), and area under the curve 0.84 (0.77) for internal validation (simulated prospective validation). For 2-year DFS prediction, the values of accuracy, sensitivity, specificity, and area under the curve were 67.9% (63.9%), 50.0% (56.3%), 85.7% (70.0%), and 0.75 (0.72), respectively, for internal validation (simulated prospective validation). CONCLUSION This study revealed that the proposed artificial neural network models constructed with 15 clinical HCC relevant features could achieve an acceptable prediction performance for DFS. Such models can support clinical physicians to deal with clinical decision-making processes on the prognosis of HCC patients receiving RFA treatments.
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Affiliation(s)
- Chiueng-Fang Wu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Jen Wu
- Department of Medical Imaging, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Horng Wu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Shinn-Forng Peng
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Wen Chiu
- Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan.
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46
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De Carlis L, Di Sandro S, Centonze L, Lauterio A, Buscemi V, De Carlis R, Ferla F, Sguinzi R, Okolicsanyi S, Belli L, Strazzabosco M. Liver-allocation policies for patients affected by HCC in Europe. CURRENT TRANSPLANTATION REPORTS 2016; 3:313-318. [PMID: 28473952 PMCID: PMC5410888 DOI: 10.1007/s40472-016-0117-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The main goal of organ allocation systems is to guarantee an equal access to the limited resource of liver grafts for every patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need, and fairness. The European heath care scenario is very complex, as it is essentially decentralized and each Nation and Regions inside the nation, operate on a significant degree of autonomy. Furthermore the epidemiology of liver diseases and HCC, which is different among European countries, clearly inpacts on indications and priorities. The aims of this review are to analyze liver allocation policies for hepatocellular carcinoma, among different European. The European area considered for this analysis included 5 macro-areas or countries, which have similar policies for liver sharing and allocation: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement français des Greffes (EfG) in France; NHS Blood & Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland). Each identified area, as network for organ sharing in Europe, adopts an allocation system based either on a policy center oriented or on a policy patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. Despite the absence of a common organs allocation policy over the Eurpean countries, long-term survival patients listed for transplant due to HCC are comparable to the long-term survival reported in the UNOS register. However, as the principles of allocation are being re-discussed and new proposals emerge, and the epidemiology of liver disease changes, an effort toward a common system is highly advisable.
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Affiliation(s)
- Luciano De Carlis
- International Center for Digestive Health, Department of Medicine
and Surgery, University of Milan-Bicocca, Milan, Italy
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Stefano Di Sandro
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
- Department of Surgical Sciences, University of Pavia, Italy
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Vincenzo Buscemi
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
- Department of Surgical Sciences, University of Pavia, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
- Department of Surgical Sciences, University of Pavia, Italy
| | - Fabio Ferla
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Raffaella Sguinzi
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Stefano Okolicsanyi
- International Center for Digestive Health, Department of Medicine
and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Luca Belli
- Department of General Surgery and Transplantation, Niguarda
Ca’ Granda Hospital, Milan, Italy
| | - Mario Strazzabosco
- International Center for Digestive Health, Department of Medicine
and Surgery, University of Milan-Bicocca, Milan, Italy
- Liver Center, Department of Medicine, Yale University School of
Medicine, New Haven, CT, USA
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Sugawara Y. Living donor liver transplantation for patients with hepatocellular carcinoma-20 years after introduction of the Milan criteria. Hepatobiliary Surg Nutr 2016; 5:492-494. [PMID: 28124005 PMCID: PMC5218907 DOI: 10.21037/hbsn.2016.12.06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 11/11/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Yasuhiko Sugawara
- Department of Transplantation/Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Chuo-ku, Kumamoto 8603-8556, Japan
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EXP CLIN TRANSPLANTExp Clin Transplant 2016; 14. [DOI: 10.6002/ect.tondtdtd2016.l17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Han DH, Joo DJ, Kim MS, Choi GH, Choi JS, Park YN, Seong J, Han KH, Kim SI. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy. Yonsei Med J 2016; 57:1276-81. [PMID: 27401662 PMCID: PMC4960397 DOI: 10.3349/ymj.2016.57.5.1276] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 01/02/2016] [Accepted: 01/04/2016] [Indexed: 02/06/2023] Open
Abstract
Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.
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Affiliation(s)
- Dai Hoon Han
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
| | - Young Nyun Park
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Department of Radiological Oncology, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Hyub Han
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
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50
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Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria. Ann Surg 2016; 263:842-50. [PMID: 26779979 DOI: 10.1097/sla.0000000000001578] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To develop and validate a model to predict tumor recurrence after living donor liver transplantation (LDLT) (MoRAL) for hepatocellular carcinoma (HCC) beyond the Milan criteria (MC). BACKGROUND Some subgroups of HCC exceeding the MC experience substantial benefit from LDLT. METHODS This multicenter study included a total of 566 consecutive patients who underwent LDLT in Korea: the beyond-MC cohort (n = 205, the derivation [n = 92] and validation [n = 113] sets) and the within-MC cohort (n = 361). The primary endpoint was time-to-recurrence. RESULTS Using multivariate Cox proportional hazard model, we derived the MoRAL score using serum levels of protein induced by vitamin K absence-II and alpha-fetoprotein, which provided a good discriminant function on time-to-recurrence (concordance index = 0.88). Concordance index was maintained similarly on both internal and external validations (mean 0.87 and 0.84, respectively). At cut off of 314.8 (75th percentile value), a low MoRAL score (≤314.8) was associated with significantly longer recurrence-free (versus > 314.8, HR = 5.29, P < 0.001) and overall survivals (HR = 2.59, P = 0.001) in the beyond-MC cohort. The 5-year recurrence-free and overall survival rates of beyond-MC patients with a low MoRAL score were as high as 66.3% and 82.6%, respectively. The within-MC patients with a high MoRAL score showed a higher risk of recurrence than beyond-MC patients with a low MoRAL score (HR = 2.56, P = 0.035). The MoRAL score was significantly correlated with explant histology. CONCLUSIONS This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.
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