|
1
|
Yin C, Armstrong S, Shin R, Geng X, Wang H, Satoskar RS, Fishbein T, Smith C, Banovac F, Kim AY, He AR. Bridging and downstaging with TACE in early and intermediate stage hepatocellular carcinoma: Predictors of receiving a liver transplant. Ann Gastroenterol Surg 2023; 7:295-305. [PMID: 36998293 PMCID: PMC10043769 DOI: 10.1002/ags3.12622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 09/05/2022] [Indexed: 11/27/2022] Open
Abstract
Background and Aims In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.
Collapse
Affiliation(s)
- Chao Yin
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Samantha Armstrong
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Richard Shin
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Xue Geng
- Department of BiostatisticsGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Hongkun Wang
- Department of BiostatisticsGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Rohit S. Satoskar
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Thomas Fishbein
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Coleman Smith
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Filip Banovac
- Department of RadiologyGeorgetown University Medical CenterWashingtonDistrict of ColumbiaUSA
| | - Alexander Y. Kim
- Department of RadiologyGeorgetown University Medical CenterWashingtonDistrict of ColumbiaUSA
| | - Aiwu Ruth He
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| |
Collapse
|
|
2
|
Mahn R, Sadeghlar F, Bartels A, Zhou T, Weismüller T, Kupczyk P, Meyer C, Gaertner FC, Toma M, Vilz T, Knipper P, Glowka T, Manekeller S, Kalff J, Strassburg CP, Gonzalez-Carmona MA. Multimodal and systemic therapy with cabozantinib for treatment of recurrent hepatocellular carcinoma after liver transplantation: A case report with long term follow-up outcomes. Medicine (Baltimore) 2021; 100:e27082. [PMID: 34559100 PMCID: PMC8462617 DOI: 10.1097/md.0000000000027082] [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: 06/22/2021] [Accepted: 08/12/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major therapeutic challenge. In recent years, new molecular-targeted therapies, such as cabozantinib, have been approved for the treatment of advanced HCC. However, clinical experience with these new drugs in the treatment of HCC in the LT setting is very limited. PATIENT CONCERNS In 2003, a 36-year-old woman was referred to the hospital with right upper abdominal pain. DIAGNOSIS An initial ultrasound of the liver demonstrated a large unclear lesion of the left lobe of the liver. The magnet resonance imaging findings confirmed a multifocal inoperable HCC in a non-cirrhotic liver. Seven years after receiving a living donor LT, pulmonary and intra-hepatic recurrence of the HCC was radiologically diagnosed and histologically confirmed. INTERVENTIONS Following an interdisciplinary therapy concept consisting of surgical, interventional-radiological (with radiofrequency ablation [RFA]) as well as systemic treatment, the patient achieved a survival of more than 10 years after tumor recurrence. As systemic first line therapy with sorafenib was accompanied by grade 3 to 4 toxicities, such as mucositis, hand-foot skin reaction, diarrhea, liver dysfunction, and hyperthyroidism, it had to be discontinued. After switching to cabozantinib from June 2018 to April 2020, partial remission of all tumor manifestations was achieved. The treatment of the remaining liver metastasis could be completed by RFA. The therapy with cabozantinib was well tolerated, only mild arterial hypertension and grade 1 to 2 mucositis were observed. Liver transplant function was stable during the therapy, no drug interaction with immunosuppressive drugs was observed. OUTCOMES More than 10 years survival after recurrence of HCC after living-donor LT due to intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy with cabozantinib in the second line therapy. LESSONS In conclusion, this report highlights the tolerability and effectiveness of cabozantinib for the treatment of HCC recurrence after LT. We show that our patient with a late recurrence of HCC after LT benefitted from intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy.
Collapse
Affiliation(s)
- Robert Mahn
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | | | - Alexandra Bartels
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | - Taotao Zhou
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | - Tobias Weismüller
- Department of Internal Medicine I, University Hospital Bonn, Germany
| | | | - Carsten Meyer
- Department of Radiology, University Hospital Bonn, Germany
| | | | - Marieta Toma
- Department of Pathology, University Hospital Bonn, Germany
| | - Tim Vilz
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | - Petra Knipper
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | - Tim Glowka
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | | | - Jörg Kalff
- Department of Visceral Surgery, University Hospital Bonn, Germany
| | | | | |
Collapse
|
|
3
|
Combining Sorafenib and Immunosuppression in Liver Transplant Recipients with Hepatocellular Carcinoma. Pharmaceuticals (Basel) 2021; 14:ph14010046. [PMID: 33435321 PMCID: PMC7826978 DOI: 10.3390/ph14010046] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/05/2021] [Accepted: 01/06/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) recurrence after liver transplantation occurs in approximately 20% of patients. Most of these patients use immunosuppressant drugs. Meanwhile, patients with HCC recurrence are frequently treated with the small molecule kinase inhibitor (SMKI) sorafenib. However, sorafenib and many immunosuppressants are substrates of the same enzymatic pathways (e.g., CYP3A4), which may potentially result in altered SMKI or immunosuppressant plasma levels. Therefore, we investigated changes in drug exposure of both sorafenib and immunosuppressants over time in four patients with systemic immunosuppressant and sorafenib treatment after HCC recurrence. In this study, sorafenib exposure declined over time during combined treatment with immunosuppressants, while two patients also experienced declining tacrolimus plasma levels. Importantly, patients were unable to increase the sorafenib dose higher than 200 mg b.i.d. without experiencing significant toxicity. We recommend to treat patients using both sorafenib and immunosuppressants with a sorafenib starting dose of 200 mg b.i.d.
Collapse
|
|
4
|
Liver Allograft Failure After Nivolumab Treatment-A Case Report With Systematic Literature Research. Transplant Direct 2018; 4:e376. [PMID: 30255136 PMCID: PMC6092180 DOI: 10.1097/txd.0000000000000814] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 05/29/2018] [Accepted: 05/30/2018] [Indexed: 02/06/2023] Open
Abstract
Background Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited. Methods We report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage. Results A systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss. Conclusion Experience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.
Collapse
|
|
5
|
Satapathy SK, Das K, Kocak M, Helmick RA, Eason JD, Nair SP, Vanatta JM. No apparent benefit of preemptive sorafenib therapy in liver transplant recipients with advanced hepatocellular carcinoma on explant. Clin Transplant 2018; 32:e13246. [PMID: 29577449 DOI: 10.1111/ctr.13246] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. AIM Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. METHODS We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. RESULTS During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. CONCLUSION Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.
Collapse
Affiliation(s)
- Sanjaya K Satapathy
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Kanak Das
- Division of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Mehmet Kocak
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Ryan A Helmick
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - James D Eason
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Satheesh P Nair
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Jason M Vanatta
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| |
Collapse
|
|
6
|
Ziogas IA, Tsoulfas G. Evolving role of Sorafenib in the management of hepatocellular carcinoma. World J Clin Oncol 2017; 8:203-213. [PMID: 28638790 PMCID: PMC5465010 DOI: 10.5306/wjco.v8.i3.203] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/03/2017] [Accepted: 04/23/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality. Although there is a broad spectrum of treatment options to choose from, only a few patients are eligible candidates to receive a curative therapy according to their stage of disease, and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer. Sorafenib, a multikinase inhibitor, is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease. It has been shown to improve the overall survival, but with various side effects, while its cost is not negligible. Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy. Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection, liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents. In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.
Collapse
|
|
7
|
Wedd JP, Nordstrom E, Nydam T, Durham J, Zimmerman M, Johnson T, Thomas Purcell W, Biggins SW. Hepatocellular carcinoma in patients listed for liver transplantation: Current and future allocation policy and management strategies for the individual patient. Liver Transpl 2015; 21:1543-52. [PMID: 26457885 DOI: 10.1002/lt.24356] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 09/10/2015] [Accepted: 09/14/2015] [Indexed: 12/12/2022]
Abstract
Liver transplantation can provide definitive cure for patients with cirrhosis and hepatocellular carcinoma (HCC) when used appropriately. Advances in the management of HCC have allowed improved control of HCC while waiting for liver transplantation and new approaches to candidate selection particularly with regard to tumor burden and downstaging protocols. Additionally, there have been recent changes in allocation policy related to HCC in the U.S. that cap the HCC MELD exception at 34 points and implement a 6-month delay in a HCC MELD exception. This review examines the U.S. liver transplant allocation policy related to HCC, comprehensively details locoregional therapy options in HCC patients awaiting liver transplantation, and considers the impact of an increasing burden of HCC on future liver graft allocation policy.
Collapse
Affiliation(s)
- Joel P Wedd
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Eric Nordstrom
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| | - Trevor Nydam
- Department of Surgery, University of Colorado, Aurora, CO
| | - Janette Durham
- Department of Interventional Radiology, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | | | - Thor Johnson
- Department of Interventional Radiology, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | - W Thomas Purcell
- Division of Medical Oncology, University of Colorado, Aurora, CO
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| |
Collapse
|
|
8
|
Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J Hepatol 2015; 7:2648-2663. [PMID: 26609342 PMCID: PMC4651909 DOI: 10.4254/wjh.v7.i26.2648] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
Collapse
Affiliation(s)
- Lisa P Waller
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Vrushak Deshpande
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| |
Collapse
|
|
9
|
Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
Collapse
|
|
10
|
Diaz G, Levitsky J, Oniscu G. Meeting report of the 2014 joint international congress of the International Liver Transplantation Society, Liver Intensive Care Group of Europe, and European Liver and Intestinal Association. Liver Transpl 2015; 21:991-1000. [PMID: 25857840 DOI: 10.1002/lt.24144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 03/30/2015] [Indexed: 01/13/2023]
Abstract
The 2014 Annual Meeting of the International Liver Transplantation Society was held in London, England. This was the 20th meeting of the Society and was marked by a joint meeting including the European Liver and Intestinal Association as well as the Liver Intensive Care Group of Europe. The meeting included symposia, invited lectures, debates, oral presentations, and posters. The principal themes were living donation, expanding the deceased donor pool, machine preservation, and new oral therapies for hepatitis C virus. This report highlights the scientific discussions of this meeting.
Collapse
Affiliation(s)
- Geraldine Diaz
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL
| | - Josh Levitsky
- Department of Gastroenterology and Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Gabriel Oniscu
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| |
Collapse
|
|
11
|
Yeh MM, Yeung RS, Apisarnthanarax S, Bhattacharya R, Cuevas C, Harris WP, Hon TLK, Padia SA, Park JO, Riggle KM, Daoud SS. Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience. World J Hepatol 2015; 7:1460-83. [PMID: 26085907 PMCID: PMC4462686 DOI: 10.4254/wjh.v7.i11.1460] [Citation(s) in RCA: 15] [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: 08/29/2014] [Revised: 04/03/2015] [Accepted: 04/27/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.
Collapse
Affiliation(s)
- Matthew M Yeh
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Raymond S Yeung
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Smith Apisarnthanarax
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Renuka Bhattacharya
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Carlos Cuevas
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - William P Harris
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Tony Lim Kiat Hon
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Siddharth A Padia
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - James O Park
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Kevin M Riggle
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Sayed S Daoud
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| |
Collapse
|
|
12
|
Guerrero-Misas M, Rodríguez-Perálvarez M, De la Mata M. Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation. World J Hepatol 2015; 7:649-661. [PMID: 25866602 PMCID: PMC4388993 DOI: 10.4254/wjh.v7.i4.649] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 12/15/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the only therapeutic option which allows to treat both, the hepatocellular carcinoma and the underlying liver disease. Indeed, liver transplantation is considered the standard of care for a subset of patients with cirrhosis and hepatocellular carcinoma. However, tumour recurrence rates are as high as 20%, and once the recurrence is established the therapeutic options are scarce and with little impact on prognosis. Strategies to minimize tumour recurrence and thus to improve outcome may be classified into 3 groups: (1) An adequate selection of candidates for liver transplantation by using the Milan criteria; (2) An optimized management within waiting list including prioritization of patients at high risk of tumour progression, and the implementation of bridging therapies, particularly when the expected length within the waiting list is longer than 6 mo; and (3) Tailored immunosuppression comprising reduced exposure to calcineurin inhibitors, particularly early after liver transplantation, and the addition of mammalian target of rapamycin inhibitors. In the present manuscript the available scientific evidence supporting these strategies is comprehensively reviewed, and future directions are provided for novel research approaches, which may contribute to the final target: to cure more patients with hepatocellular carcinoma and with an improved long term outcome.
Collapse
Affiliation(s)
- Marta Guerrero-Misas
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel Rodríguez-Perálvarez
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| |
Collapse
|