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1
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Melehy A, Agopian VG. Role of Liver Transplant in Primary and Secondary Liver Malignancies. Clin Liver Dis 2025; 29:217-234. [PMID: 40287268 DOI: 10.1016/j.cld.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the primary hepatic malignancies with established pathways to transplantation and model for end-stage liver disease (MELD) exception points. Other tumors managed with liver transplantation (LT) include hepatic epithelioid hemangioendothelioma and fibrolamellar HCC. LT for metastatic neuroendocrine tumor has been established with patient selection criteria and a path to MELD exception points. Additionally, recent data on LT for patients with unresectable hepatic colorectal metastases demonstrate increasingly encouraging initial results.
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Affiliation(s)
- Andrew Melehy
- Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, David Geffen School of Medicine at University of California, Los Angeles, CA, USA
| | - Vatche G Agopian
- Division of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
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2
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Ito T, Taura K, Fukumitsu K, Okumura S, Ogiso S, Anazawa T, Nagai K, Uchida Y, Ishii T, Hatano E. Safety and efficacy of living donor liver transplantation for unresectable perihilar cholangiocarcinoma: A single center prospective study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2025; 32:276-286. [PMID: 39996522 PMCID: PMC12038382 DOI: 10.1002/jhbp.12121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
BACKGROUND The prognosis for unresectable perihilar cholangiocarcinoma (phCCA) is extremely poor. Liver transplantation in combination with neoadjuvant chemoradiation therapy has become the treatment of choice for unresectable phCCA in the USA. In 2018, we launched a prospective study to evaluate the safety and efficacy of living donor liver transplantation (LDLT) for unresectable phCCA. METHODS A total of 10 patients were enrolled in this study between 2018 and 2024. Finally, five patients with unresectable phCCA underwent LDLT after neoadjuvant chemotherapy, radiation, and staging laparotomy, while the other five patients dropped out of the protocol. RESULTS The median follow-up period was 23.7 months. The overall survival rate for the five patients who underwent LDLT was 100% after one year. Hepatic artery thrombosis and delayed gastric emptying occurred in two and three cases, respectively. The histological efficacy of preoperative treatment was grade IIb and III, according to the Evans classification, in all five patients. All surgical margins and dissected lymph nodes were negative. Four patients were alive with no evidence of disease recurrence while one patient had recurrence 10 months after LDLT. CONCLUSIONS LDLT is feasible and may be a last-resort treatment option for unresectable phCCA, although the long-term outcomes need to be carefully monitored. CLINICAL TRIAL REGISTER AND CLINICAL REGISTRATION NUMBER The UMIN registration number for this study is 000033348.
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Affiliation(s)
- Takashi Ito
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of Gastroenterological Surgery and OncologyMedical Research Institute, Kitano HospitalOsakaJapan
| | - Ken Fukumitsu
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of SurgeryGastrointestinal Center, Kyoto Katsura HospitalKyotoJapan
| | - Shinya Okumura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Yoichiro Uchida
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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3
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Patrono D, De Stefano N, Romagnoli R. Liver transplantation for tumor entities. Curr Opin Organ Transplant 2024; 29:255-265. [PMID: 38716718 DOI: 10.1097/mot.0000000000001149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2024]
Abstract
PURPOSE OF REVIEW Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology. RECENT FINDINGS Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection. SUMMARY While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.
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Affiliation(s)
- Damiano Patrono
- General Surgery 2U - Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino - University of Turin, Turin, Italy
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Esmail A, Badheeb M, Alnahar B, Almiqlash B, Sakr Y, Khasawneh B, Al-Najjar E, Al-Rawi H, Abudayyeh A, Rayyan Y, Abdelrahim M. Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation. Cancers (Basel) 2024; 16:1946. [PMID: 38893067 PMCID: PMC11171350 DOI: 10.3390/cancers16111946] [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: 04/09/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06605, USA
| | - Batool Alnahar
- College of Medicine, Almaarefa University, Riyadh 13713, Saudi Arabia
| | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Bayan Khasawneh
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Hadeel Al-Rawi
- Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
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5
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Boutin M, Krishnan T, Safro M, Yang J, Jafari H, Davies JM, Gill S. Real-world experience supporting the role of oncologic resection and adjuvant chemotherapy in biliary tract cancers. Ther Adv Med Oncol 2024; 16:17588359241247008. [PMID: 38628554 PMCID: PMC11020734 DOI: 10.1177/17588359241247008] [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: 10/19/2023] [Accepted: 03/27/2024] [Indexed: 04/19/2024] Open
Abstract
Background Complete resection followed by adjuvant chemotherapy is the gold standard for patients with localized cholangiocarcinoma (CC) or gallbladder cancer (GBC). However, this is not always feasible, and recurrence rates remain high. Objectives To understand the real-world proportions and reason for treatment failure in resected biliary tract cancers. Design and methods We performed a retrospective population-based review of patients with GBC or CC [intrahepatic (IHCC) or extrahepatic (EHCC)] resected between 2005 and 2019 using the BC Cancer provincial database. A chart review was conducted to characterize demographics, treatments received and outcomes. Results In total, 594 patients were identified of whom 416 (70%) had disease recurrence. Most GBCs (96%) were diagnosed incidentally, and repeat oncologic resection was performed in 45%. Adjuvant chemotherapy was received in 51% of patients diagnosed after 2017 (mostly capecitabine). Patient co-morbidities, disease progression and patient preference were the commonest reasons for not proceeding with adjuvant chemotherapy. One-third of patients did not complete all planned cycles. Median overall survival was significantly higher in those with complete (R0) versus incomplete (R1) resection [31.6 versus 18 months, hazard ratio (HR): 0.43, 95% confidence interval (CI): 0.35-0.53] and in those with versus without re-resection for GBC [29.4 versus 19 months, HR: 0.55, 95% CI: 0.41-0.73]. There was a trend towards improved survival with versus without adjuvant therapy (HR: 0.79, 95% CI: 0.61-1.02). Only 25% in the more contemporary cohort (2017-2019) had an R0 resection and completed adjuvant chemotherapy. Conclusion Complete resection, including reresection for incidentally diagnosed GBCs, and adjuvant chemotherapy were associated with improved outcomes in this retrospective cohort, yet many patients were not able to complete these treatments. Neoadjuvant strategies may improve treatment delivery and ultimately, outcomes.
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Affiliation(s)
| | | | | | - Jenny Yang
- Department of Medical Oncology, University of British Columbia, Vancouver, BC, Canada
| | - Helia Jafari
- Department of Medical Oncology, University of British Columbia, Vancouver, BC, Canada
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 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
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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7
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de Jong DM, den Hoed CM, Willemssen FEJA, Thomeer MGJ, Bruno MJ, Koerkamp BG, de Jonge J, Alwayn IPJ, van Hooft JE, Hoogwater F, van der Heide F, Inderson A, van Vilsteren FGI, van Driel LMJW. Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma. Gastrointest Endosc 2024; 99:548-556. [PMID: 37890597 DOI: 10.1016/j.gie.2023.10.047] [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: 07/16/2023] [Revised: 09/02/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND AND AIMS For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. METHODS In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a "suspicious" nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. RESULTS A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. CONCLUSIONS Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.
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Affiliation(s)
- David M de Jong
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Caroline M den Hoed
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands; Erasmus MC Transplant Institute, Rotterdam, The Netherlands
| | - Francois E J A Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Maarten G J Thomeer
- Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Erasmus MC Transplant Institute, Rotterdam, The Netherlands; Department of Surgery, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands
| | - Ian P J Alwayn
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Frederik Hoogwater
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen, The Netherlands
| | - Frans van der Heide
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Akin Inderson
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Frederike G I van Vilsteren
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands.
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8
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Wu TC, Smith CP, Li JS, Burton J, Jackson NJ, Tao R, Ludmir EB, Raldow AC. A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols. J Surg Oncol 2024; 129:574-583. [PMID: 37986552 DOI: 10.1002/jso.27511] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 09/26/2023] [Accepted: 11/04/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.
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Affiliation(s)
- Trudy C Wu
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
| | - Clayton P Smith
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
| | - Joshua S Li
- Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, California, USA
| | - Jason Burton
- Louise M. Darling Biomedical Library, University of California Los Angeles, Los Angeles, California, USA
| | - Nicholas J Jackson
- Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, California, USA
| | - Randa Tao
- Department of Radiation Oncology, University of Utah, Salt Lake City, Utah, USA
| | - Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ann C Raldow
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
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9
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Ramjeesingh R, Chaudhury P, Tam VC, Roberge D, Lim HJ, Knox JJ, Asselah J, Doucette S, Chhiber N, Goodwin R. A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada. Curr Oncol 2023; 30:7132-7150. [PMID: 37622998 PMCID: PMC10453186 DOI: 10.3390/curroncol30080517] [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: 06/17/2023] [Revised: 07/17/2023] [Accepted: 07/20/2023] [Indexed: 08/26/2023] Open
Abstract
Biliary tract cancers (BTC) are rare and aggressive tumors with poor prognosis. Radical surgery offers the best chance for cure; however, most patients present with unresectable disease, and among those receiving curative-intent surgery, recurrence rates remain high. While other locoregional therapies for unresectable disease may be considered, only select patients may be eligible. Consequently, systemic therapy plays a significant role in the treatment of BTC. In the adjuvant setting, capecitabine is recommended following curative-intent resection. In the neoadjuvant setting, systemic therapy has mostly been explored for downstaging in borderline resectable tumours, although evidence for its routine use is lacking. For advanced unresectable or metastatic disease, gemcitabine-cisplatin plus durvalumab has become the standard of care, while the addition of pembrolizumab to gemcitabine-cisplatin has also recently demonstrated improved survival compared to chemotherapy alone. Following progression on gemcitabine-cisplatin, several chemotherapy combinations and biomarker-driven targeted agents have been explored. However, the optimum regimen remains unclear, and access to targeted agents remains challenging in Canada. Overall, this article serves as a practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease.
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Affiliation(s)
- Ravi Ramjeesingh
- Division of Medical Oncology, Department of Medicine, Nova Scotia Health, Dalhousie University, Halifax, NS B3H 2Y9, Canada
| | - Prosanto Chaudhury
- Department of Surgery and Oncology, McGill University Health Centre, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada
| | - Vincent C. Tam
- Division of Medical Oncology, Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - David Roberge
- Department of Radiology, Radiation Oncology and Nuclear Medicine, University of Montreal, Montreal, QC H3T 1A4, Canada
| | - Howard J. Lim
- Division of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada
| | - Jennifer J. Knox
- Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada
| | - Jamil Asselah
- Department of Medicine, Division of Medical Oncology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
| | - Sarah Doucette
- IMPACT Medicom Inc., Toronto, ON M6S 3K2, Canada; (S.D.)
| | - Nirlep Chhiber
- IMPACT Medicom Inc., Toronto, ON M6S 3K2, Canada; (S.D.)
| | - Rachel Goodwin
- Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON K1H 8L6, Canada
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10
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Patrono D, Colli F, Colangelo M, De Stefano N, Apostu AL, Mazza E, Catalano S, Rizza G, Mirabella S, Romagnoli R. How Can Machine Perfusion Change the Paradigm of Liver Transplantation for Patients with Perihilar Cholangiocarcinoma? J Clin Med 2023; 12:jcm12052026. [PMID: 36902813 PMCID: PMC10004136 DOI: 10.3390/jcm12052026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.
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11
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Giovinazzo F, Pascale MM, Cardella F, Picarelli M, Molica S, Zotta F, Martullo A, Clarke G, Frongillo F, Grieco A, Agnes S. Current Perspectives in Liver Transplantation for Perihilar Cholangiocarcinoma. Curr Oncol 2023; 30:2942-2953. [PMID: 36975438 PMCID: PMC10047046 DOI: 10.3390/curroncol30030225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/17/2023] [Accepted: 01/30/2023] [Indexed: 03/05/2023] Open
Abstract
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are considered unresectable at the time of diagnosis or exploration. When resective surgery is deemed unfeasible, liver transplantation (LT) could be an effective alternative. The overall survival rates after LT at 1 and 3 years are 91% and 81%, respectively. The overall five-year survival rate after transplantation is 73% (79% for patients with underlying PSC and 63% for de novo pCCA). Multicenter case series reported a 5-year disease-free survival rate of ~65%. However, different protocols, including neoadjuvant therapy, have been proposed. The scarcity of organ availability represents a crucial limiting factor in recommending LT preferentially in treating pCCA. Living donor transplantations and marginal cadaveric allografts have proven to be exciting options to overcome organ shortage. Management of jaundice and cholangitis is still challenging for these patients and could impact LT listing. Whether to adopt surgical resection or LT as standard-of-care in pCCA is still a matter of debate, and more prospective studies are needed.
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Affiliation(s)
- Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Marco Maria Pascale
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, 80138 Naples, Italy
| | - Matteo Picarelli
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Serena Molica
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Zotta
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Annamaria Martullo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - George Clarke
- Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, UK
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Grieco
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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12
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Mauro E, Ferrer-Fàbrega J, Sauri T, Soler A, Cobo A, Burrel M, Iserte G, Forner A. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers (Basel) 2023; 15:1244. [PMID: 36831586 PMCID: PMC9953927 DOI: 10.3390/cancers15041244] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/03/2023] [Accepted: 02/11/2023] [Indexed: 02/18/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15-35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.
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Affiliation(s)
- Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
| | - Tamara Sauri
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Medical Oncology Department, ICMHO, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alexandre Soler
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Amparo Cobo
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Nuclear Medicine Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Department of Interventional Radiology, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Gemma Iserte
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
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13
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Tchelebi LT, Jethwa KR, Levy AT, Anker CJ, Kennedy T, Grodstein E, Hallemeier CL, Jabbour SK, Kim E, Kumar R, Lee P, Small W, Williams VM, Sharma N, Russo S. American Radium Society (ARS) Appropriate Use Criteria (AUC) for Extrahepatic Cholangiocarcinoma. Am J Clin Oncol 2023; 46:73-84. [PMID: 36534388 PMCID: PMC9855763 DOI: 10.1097/coc.0000000000000969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.
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Affiliation(s)
| | - Krishan R. Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | | | - Christopher J. Anker
- Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Elliot Grodstein
- Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | - Salma K. Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Rachit Kumar
- Department of Radiation Oncology, Banner MD Anderson Cancer Center, Phoenix, AZ
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | | | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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14
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Cremen S, Kelly ME, Gallagher TK. The role of neo-adjuvant therapy in cholangiocarcinoma: A systematic review. Front Oncol 2022; 12:975136. [PMID: 36568243 PMCID: PMC9779982 DOI: 10.3389/fonc.2022.975136] [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: 06/21/2022] [Accepted: 11/17/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Cholangiocarcinoma (CCA) is the most common malignancy affecting the biliary tree. The only curative treatment is surgical resection, aiming for negative margins (R0). For those who have locally advanced disease, which is borderline resectable, neoadjuvant chemoradiation presents an opportunity to reduce tumour size and allow for surgical resection. The aim of this review is to establish the role of neoadjuvant therapy in each subtype of CCA and establish its impact on survival. Methods Search terms such as 'neoadjuvant therapy' and 'cholangiocarcinoma' were searched on multiple databases, including Pubmed, Ovid and Embase. They were then reviewed separately by two reviewers for inclusion criteria. 978 studies were initially identified from the search strategy, with 21 being included in this review. Results 5,009 patients were included across 21 studies. 1,173 underwent neoadjuvant therapy, 3,818 had surgical resection alone. 359 patients received Gemcitabine based regimes, making it the most commonly utilised regimen for patients CCA and Biliary Tract Cancer (BTC). Data on tolerability of regimes was limited. All included papers were found to have low risk of bias when assessed using The Newcastle Ottawa Scale. Patients who underwent neoadjuvant therapy had a similar median overall survival compared to those who underwent upfront surgery (38.4 versus 35.1 months respectively). Pre-operative CA19-9, microvascular invasion, perineurial invasion and positive lymph nodes were of prognostic significance across BTC and CCA subtypes. Conclusion Neoadjuvant therapy and surgical resection is associated with improved patient outcomes and longer median overall survival compared to therapy and upfront surgery, however heterogeneity between research papers limited the ability to further analyse the significance of these results. Although initial studies are promising, further research is required in order to define suitable treatment protocols and tolerability of neoadjuvant regimes. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42020164781.
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Affiliation(s)
- Sinead Cremen
- Department of Hepatobiliary Surgery, St. Vincent’s University Hospital, Dublin, Ireland
| | - Michael E. Kelly
- Department of Surgery, Tallaght University Hospital, Tallaght, Dublin, Ireland
| | - Tom K. Gallagher
- Department of Hepatobiliary Surgery, St. Vincent’s University Hospital, Dublin, Ireland,*Correspondence: Tom K. Gallagher,
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15
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Tam VC, Ramjeesingh R, Burkes R, Yoshida EM, Doucette S, Lim HJ. Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective. Curr Oncol 2022; 29:7072-7085. [PMID: 36290832 PMCID: PMC9600578 DOI: 10.3390/curroncol29100555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/18/2022] [Accepted: 09/20/2022] [Indexed: 01/13/2023] Open
Abstract
Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access.
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Affiliation(s)
- Vincent C. Tam
- Division of Medical Oncology, Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Ravi Ramjeesingh
- Division of Medical Oncology, Department of Medicine, Nova Scotia Health, Dalhousie University, Halifax, NS B3H 2Y9, Canada
| | - Ronald Burkes
- Division of Medical Oncology, Princess Margaret Cancer Centre, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
| | - Eric M. Yoshida
- Division of Gastroenterology, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada
- Medical Advisory Committee Chair, Canadian Liver Foundation, Markham, ON L3R 8T3, Canada
| | | | - Howard J. Lim
- Division of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada
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16
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Eguchi S, Hidaka M, Hara T, Matsushima H, Soyama A. Liver transplantation for intrahepatic and hilar cholangiocellular carcinoma: Most recent updates in the literature. Ann Gastroenterol Surg 2022; 6:616-622. [PMID: 36091305 PMCID: PMC9444854 DOI: 10.1002/ags3.12567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 11/24/2022] Open
Abstract
Liver transplantation (LT) for non-hepatocellular carcinoma is still a debatable indication. Recently, hilar cholangiocellular carcinoma (hCCC) has attracted interest as a new indication for LT, but LT in this case should be carefully considered. Based on the recent meta-analysis for intrahepatic CCC (IHCCC) and our results from incidental IHCCC transplanted for other diseases such as primary sclerosing cholangitis, the indication for LT for IHCCC should be limited to a single tumor less than 2 cm. For hCCC, with pre-transplant chemoradiotherapy and careful selection criteria, long-term survival after LT could be attained. In order to improve the results of LT for intrahepatic and hCCC, further studies are required on the ingenuity of immunosuppressive therapy combined with chemotherapy, and optimal treatment methods to prevent recurrence, as well as initial case selection.
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Affiliation(s)
- Susumu Eguchi
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Masaaki Hidaka
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Takanobu Hara
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Hajime Matsushima
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Akihiko Soyama
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
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17
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Abdelrahim M, Esmail A, Xu J, Umoru G, Al-Rawi H, Saharia A, Abudayyeh A, Victor D, McMillan R, Kodali S, Ghobrial RM. Gemcitabine Plus Cisplatin Versus Non-Gemcitabine and Cisplatin Regimens as Neoadjuvant Treatment for Cholangiocarcinoma Patients Prior to Liver Transplantation: An Institution Experience. Front Oncol 2022; 12:908687. [PMID: 35719974 PMCID: PMC9201492 DOI: 10.3389/fonc.2022.908687] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/02/2022] [Indexed: 12/21/2022] Open
Abstract
Background Cholangiocarcinoma management is constantly being updated in view of existing evidence in order to establish practice guidelines and consensus statements. However, the available treatment guidelines to optimize outcomes for cholangiocarcinoma patients who require liver transplantation are still controversial. This study contributing to the cholangiocarcinoma care field by investigating a new promising neoadjuvant therapy that might be help to grant the liver transplant option to the patients with cholangiocarcinoma. Here, we evaluate and compare the potential efficacy of chemotherapy combination of Gemcitabine plus Cisplatin versus non- Gemcitabine and Cisplatin regimens as a neo-adjuvant treatment for cholangiocarcinoma patients prior to liver transplantation. Methods In this retrospective study, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with either the combination of neo-adjuvant Gemcitabine plus Cisplatin with no radiation or other standard options of neo-adjuvant treatment. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center in collaboration with the same institution’s transplant center according to an open-labeled, and centers-approved clinical management protocol. Patients were listed for liver transplantation if they had a minimum of six months of scans showing response or confirmation of disease stability. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. This report, which was censored on March 18, 2022. Results Out of a total of 707 liver transplant recipients were screened, 37 patients were confirmed with a diagnosis of cholangiocarcinoma and only 18 patients (11 males and 7 females) with a median age of 61.83 [interquartile range: 58.27-68.74] met inclusion criteria. Of the 18 patients enrolled, 10 received Gemcitabine/Cisplatin, while 8 patients received either Gemcitabine monotherapy or Capecitabine or FOLFIRI. Months for recurrence after transplantation was 20.1 (IRQ: 20.1-20.1) in the Gemcitabine/Cisplatin group and 9.5 (8.9-12.47) months in the non-Gemcitabine/Cisplatin group (p-value=0.18). Median months of follow-up in the Gemcitabine/Cisplatin group was 28.35 (27.1-32.23) months versus 40.12 (20.6-56.22) months in the non-Gemcitabine/Cisplatin group (p-value=0.33). In non-Gemcitabine/Cisplatin patients, overall survival was 75% (95% CI 31-93%) at both years 1 and 2; 63% (95% CI 23-86%) at years 3 to 5. In Gemcitabine/Cisplatin patients, overall survival was 100% (95% CI 100-100%) at both years 1 and 2; 75% (95% CI 13-96%) at years 3 to 5. Three non-Gemcitabine/Cisplatin patients died at 328 days, 340 days, and 896 days, respectively. One Gemcitabine/Cisplatin patient died at 885 days. Conclusion Our findings suggest improved overall survival outcomes with Gemcitabine plus Cisplatin as neo-adjuvant treatment with no concomitant radiation compared to non-Gemcitabine/Cisplatin regimens in patients with cholangiocarcinoma prior to liver transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology Department of Medical Oncology Houston Methodist Cancer Center, Houston, TX, United States.,Cockrell Center of Advanced Therapeutics Phase I program, Houston Methodist Research Institute, Houston, TX, United States.,Department of Internal Medicine, Weill Cornell Medical College, New York, NY, United States
| | - Abdullah Esmail
- Section of GI Oncology Department of Medical Oncology Houston Methodist Cancer Center, Houston, TX, United States.,Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, United States
| | - Jiaqiong Xu
- Center for Outcomes Research, Houston Methodist Research Institute, Houston, TX, United States
| | - Godsfavour Umoru
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, United States
| | - Hadeel Al-Rawi
- Section of GI Oncology Department of Medical Oncology Houston Methodist Cancer Center, Houston, TX, United States
| | - Ashish Saharia
- Department of Internal Medicine, Weill Cornell Medical College, New York, NY, United States.,Houston Methodist Hospital, JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, United States
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David Victor
- Houston Methodist Hospital, JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, United States
| | - Robert McMillan
- Department of Internal Medicine, Weill Cornell Medical College, New York, NY, United States.,Department of Pharmacy, Houston Methodist Hospital, Houston, TX, United States
| | - Sudha Kodali
- Department of Internal Medicine, Weill Cornell Medical College, New York, NY, United States.,Houston Methodist Hospital, JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, United States
| | - Rafik M Ghobrial
- Department of Internal Medicine, Weill Cornell Medical College, New York, NY, United States.,Houston Methodist Hospital, JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, United States
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18
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Lamarca A, Edeline J, Goyal L. How I treat biliary tract cancer. ESMO Open 2022; 7:100378. [PMID: 35032765 PMCID: PMC8762076 DOI: 10.1016/j.esmoop.2021.100378] [Citation(s) in RCA: 73] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 12/30/2022] Open
Abstract
Management of biliary tract cancers (BTCs) is rapidly evolving. Curative management relies on surgical resection followed by adjuvant capecitabine for cholangiocarcinoma and gallbladder cancers. Unfortunately relapse rate remains high, and better adjuvant strategies are urgently required. A majority of patients are diagnosed with advanced disease, when chemotherapy with cisplatin and gemcitabine followed by second-line 5-FU and oxaliplatin /irinotecan is the cornerstone of treatment for most patients in the absence of targetable alterations. Targeted therapies, including therapies for tumours with fibroblast growth factor receptor-2 (FGFR-2) fusions, isocitrate dehydrogenase-1 (IDH-1) mutations, B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions, Human epidermal growth factor-2 (HER-2) amplifications, and/or microsatellite instability are rapidly changing the treatment paradigm for many patients with advanced BTC, especially for patients with intrahepatic cholangiocarcinoma. Because of this, molecular profiling should be considered early on patients pathway to allow adequate planning of therapy. Ongoing research is likely to clarify the role of immunotherapy, liver-directed therapy, and liver transplant for BTCs in the future.
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Affiliation(s)
- A Lamarca
- Department of Medical Oncology, The Christie NHS Foundation, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK.
| | - J Edeline
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - L Goyal
- Department of Medical Oncology, Mass General Cancer Center, Harvard Medical School, Boston, USA
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19
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Manzia TM, Parente A, Lenci I, Sensi B, Milana M, Gazia C, Signorello A, Angelico R, Grassi G, Tisone G, Baiocchi L. Moving forward in the treatment of cholangiocarcinoma. World J Gastrointest Oncol 2021; 13:1939-1955. [PMID: 35070034 PMCID: PMC8713313 DOI: 10.4251/wjgo.v13.i12.1939] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/14/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.
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Affiliation(s)
- Tommaso M Manzia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Alessandro Parente
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Ilaria Lenci
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Bruno Sensi
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Carlo Gazia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | | | - Roberta Angelico
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Giuseppe Grassi
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Giuseppe Tisone
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
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20
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Safarpour AR, Askari H, Ejtehadi F, Azarnezhad A, Raeis-Abdollahi E, Tajbakhsh A, Abazari MF, Tarkesh F, Shamsaeefar A, Niknam R, Sivandzadeh GR, Lankarani KB, Ejtehadi F. Cholangiocarcinoma and liver transplantation: What we know so far? World J Gastrointest Pathophysiol 2021; 12:84-105. [PMID: 34676129 PMCID: PMC8481789 DOI: 10.4291/wjgp.v12.i5.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/28/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.
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Affiliation(s)
- Ali Reza Safarpour
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Hassan Askari
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Farshid Ejtehadi
- The Princess Alexandra Hospital HNS Trust, Harlow, Essex CM20 1QX, United Kingdom
| | - Asaad Azarnezhad
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj 6617913446, Iran
| | - Ehsan Raeis-Abdollahi
- Department of Basic Medical Sciences, Qom Medical Branch, Islamic Azad University, Qom, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Firoozeh Tarkesh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Alireza Shamsaeefar
- Shiraz Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran
| | - Ramin Niknam
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Gholam Reza Sivandzadeh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | | | - Fardad Ejtehadi
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
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21
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Zanetto A, Shalaby S, Gambato M, Germani G, Senzolo M, Bizzaro D, Russo FP, Burra P. New Indications for Liver Transplantation. J Clin Med 2021; 10:3867. [PMID: 34501314 PMCID: PMC8432035 DOI: 10.3390/jcm10173867] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases.
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Affiliation(s)
| | | | | | | | | | | | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (M.S.); (D.B.); (F.P.R.)
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22
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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23
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Talakić E, Janek E, Mikalauskas S, Schemmer P. Liver Transplantation in Malignancies: A Comprehensive and Systematic Review on Oncological Outcome. Visc Med 2021; 37:302-314. [PMID: 34540947 PMCID: PMC8406343 DOI: 10.1159/000517328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver transplantation (LT) is today's standard treatment for both end-stage liver disease and tumors; however, suitable grafts for LT are a scarce resource and outcome after LT is highly dependent on its underlying indication. Thus, patients must be carefully selected to optimize the number of life years gained per graft. This comprehensive and systematic review critically reflects the most recently published oncological outcome data after LT in malignancies based on the preoperative radiological findings. METHODS A systematic literature search was conducted to detect preferentially most recent high-volume series or large database analysis on oncological outcomes after LT for both primary liver cancer and liver metastases between January 1, 2019, and November 14, 2020. A comprehensive review on the radiological assessment of the reviewed liver malignancies is included and its preoperative value for an outcome-driven indication reflected. RESULTS Twenty most recent high-volume or relevant studies including a total number of 2,521 patients were identified including 4, 4, 4, 4, 3, and 1 publications on oncological outcome after LT for hepatocellular carcinoma, cholangiocellular carcinoma, hepatic epitheloid hemangioendothelioma, hepatoblastoma, and both metastatic neuroendocrine tumors and colorectal cancer, respectively. The overall survival is comparable to patients without tumors if patients with malignancies are well selected for LT; however, this is highly dependent on tumor entity, tumor stage, and both neoadjuvant and concomitant treatment. DISCUSSION/CONCLUSION LT is a promising option for better survival in patients with malignant liver tumors in selected patients; however, the indication must be critically discussed prior to LT in every single case in the context of organ shortage.
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Affiliation(s)
- Emina Talakić
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Elmar Janek
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Saulius Mikalauskas
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
| | - Peter Schemmer
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
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24
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Rizzo A, Brandi G. Neoadjuvant therapy for cholangiocarcinoma: A comprehensive literature review. Cancer Treat Res Commun 2021; 27:100354. [PMID: 33756174 DOI: 10.1016/j.ctarc.2021.100354] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 03/11/2021] [Accepted: 03/13/2021] [Indexed: 02/07/2023]
Abstract
Biliary tract cancers (BTCs) comprise a heterogenous group of aggressive and rare malignancies arising in the bile duct outside or within the liver. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC) and ampulla of Vater cancer (AVC); according to the "historical" anatomical classification, CCAs are further subdivided into extrahepatic cholangiocarcinomas (eCCAs) - including distal (dCCA) and perihilar (pCCA) - and intrahepatic cholangiocarcinomas (iCCA). Notably enough, these subtypes reflect distinct features in terms of biology, epidemiology, prognosis and therapeutic strategies. Although surgical resection remains the only potentially curative treatment option for CCA patients, radical surgery is possible for only a small proportion of cases. Moreover, it has been observed that up to 50% of patients deemed resectable at diagnosis are found to be unresectable during exploratory laparotomy. Additionally, even following radical surgery, recurrence rates are high. Neoadjuvant therapy represents an appealing approach in this setting, where this therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant therapy in CCA and several questions remains unanswered, including the activity of systemic therapy in early stages of the disease, the optimal start time of treatment, patient selection and the length of neoadjuvant therapy. In this review, we will discuss available data on neoadjuvant systemic therapy in CCA, highlighting future directions in this setting, with a particular focus on recently published data and ongoing and recruiting trials.
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Affiliation(s)
- Alessandro Rizzo
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy.
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy
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25
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Sapisochin G, Hibi T, Toso C, Man K, Berenguer M, Heimbach J, Greten TF, Pugh TJ, Dawson LA, Mazzaferro V. Transplant Oncology in Primary and Metastatic Liver Tumors: Principles, Evidence, and Opportunities. Ann Surg 2021; 273:483-493. [PMID: 33065633 DOI: 10.1097/sla.0000000000004071] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Transplant oncology defines any application of transplant medicine and surgery aimed at improving cancer patients' survival and/or quality of life. In practice, liver transplantation for selected hepato-biliary cancers is the only solid organ transplant with demonstrated efficacy in curing cancer. Four are the proposed future contributions of transplant oncology in hepato-biliary cancer (4-e). (1) evolutionary approach to cancer care that includes liver transplantation; (2) elucidation of self and non-self recognition systems, by linking tumor and transplant immunology; (3) exploration of innovative endpoints both in clinical and experimental settings taking advantage from the access to the entire liver explant; (4) extension of surgical limitation in the multidisciplinary approach to hepato-biliary oncology. The aim of this review is to define the principles of transplant oncology that may be applied to hepato-biliary cancer treatment and research, attempting to balance current evidences with future opportunities.
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Affiliation(s)
- Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Christian Toso
- Division of Abdominal Surgery and Hepato-pancreato-biliary Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
| | - Kwan Man
- Department of Surgery, HKU-SZH and LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Marina Berenguer
- Hepatology and Liver Transplantation Unit, Ciberehd, IISLaFe and Facultad de Medicina, La Fe University Hospital, Valencia, Spain
| | - Julie Heimbach
- Department of Surgery Liver Transplant Program, Mayo Clinic, Rochester, Minnesota
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research and NCI-CCR Liver Cancer Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Trevor J Pugh
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
- Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation, Department of Oncology, University of Milan, Milan, Italy and Istituto Nazionale Tumori, Fondazione IRCCS, Milan, Italy
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26
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Neoadjuvant Chemoradiotherapy and Liver Transplantation for Unresectable Hilar Cholangiocarcinoma: The Irish Experience of the Mayo Protocol. Transplantation 2021; 104:2097-2104. [PMID: 31972704 DOI: 10.1097/tp.0000000000003114] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Pioneered by the Mayo Clinic, multimodal therapy with neoadjuvant chemoradiotherapy and orthotopic liver transplant has emerged as a promising option for unresectable hilar cholangiocarcinoma (hCCA). This study reports the experience of the Irish National Liver Transplant Programme with the Mayo Protocol. METHODS All patients diagnosed with unresectable hCCA between 2004 and 2016, who were eligible for the treatment protocol, were prospectively studied. RESULTS Thirty-seven patients commenced chemoradiotherapy. Of those, 11 were excluded due to disease progression and 26 proceeded to liver transplantation. There were 24 males, the median age was 49, and 88% had underlying primary sclerosing cholangitis. R0 and pathologic complete response rates were 96% and 62%, respectively. Overall median survival was 53 months and 1-, 3-, and 5-year survival was 81%, 69%, and 55%, respectively. The median survival of patients achieving a pathologic complete response was 83.8 months compared with 20.9 months in the group with residual disease (P = 0.036). Six patients (23%) developed disease recurrence. Among the patients who developed metastatic disease during neoadjuvant treatment, median survival was 10.5 months compared with 53 months in patients who proceeded to transplant (P < 0.001). CONCLUSIONS Neoadjuvant chemoradiotherapy followed by liver transplantation substantially increases the survival of patients with unresectable hCCA. Achieving a pathologic complete response confers a significant survival benefit.
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27
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Cambridge WA, Fairfield C, Powell JJ, Harrison EM, Søreide K, Wigmore SJ, Guest RV. Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma. Ann Surg 2021; 273:240-250. [PMID: 32097164 DOI: 10.1097/sla.0000000000003801] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC). BACKGROUND Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT. METHODS MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival. RESULTS Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%-79.4%), 48.0% (95% CI 35.0%-60.9%), and 31.6% (95% CI 23.1%-40.7%). These improved to 82.8% (95% CI 73.0%-90.8%), 65.5% (95% CI 48.7%-80.5%), and 65.1% (95% CI 55.1%-74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%-30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%-69.4%) without. CONCLUSIONS In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.
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Affiliation(s)
- William A Cambridge
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | - Cameron Fairfield
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | - James J Powell
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | - Ewen M Harrison
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Stephen J Wigmore
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
| | - Rachel V Guest
- Department of Clinical Surgery, University of Edinburgh, Little France Crescent, Edinburgh, UK
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28
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Italian Clinical Practice Guidelines on Cholangiocarcinoma - Part II: Treatment. Dig Liver Dis 2020; 52:1430-1442. [PMID: 32952071 DOI: 10.1016/j.dld.2020.08.030] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/17/2020] [Accepted: 08/17/2020] [Indexed: 01/27/2023]
Abstract
Currently, the only curative treatment for cholangiocarcinoma (CCA) is surgical resection, though this treatment is possible in less than 40% of patients. However, recent improvements in preoperative management have led to a higher number of patients who are candidates for this procedure. For unresectable patients, progress is ongoing in terms of locoregional and chemoradiation treatments and target therapies, especially in the definition of patient selection criteria. This is the second part of the Italian CCA guidelines, dealing with CCA treatment, that have been formulated in accordance with Italian National Institute of Health indications and developed according to the GRADE method and related advancements.
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29
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Tan EK, Taner T, Heimbach JK, Gores GJ, Rosen CB. Liver Transplantation for Peri-hilar Cholangiocarcinoma. J Gastrointest Surg 2020; 24:2679-2685. [PMID: 32671802 DOI: 10.1007/s11605-020-04721-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 06/28/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Liver transplantation for peri-hilar cholangiocarcinoma (pCCA) following neoadjuvant chemoradiation achieves excellent long-term survival in carefully selected patients with early-stage unresectable pCCA and patients with primary sclerosing cholangitis (PSC)-associated pCCA. Strict adherence to selection criteria, aggressive neoadjuvant therapy, operative staging prior to transplantation, and several technical accommodations during the transplant operation are necessary for success. In this review, we provide a contemporaneous overview of liver transplantation for pCCA, including selection criteria, neoadjuvant therapy, operative staging, and technical aspects of liver transplantation unique to patients with pCCA and an irradiated operative field. We also discuss several evolving trends intended to improve patient outcomes. RESULTS AND CONCLUSION Intention-to-treat and patient outcomes after liver transplantation for PSC-associated pCCA are superior to de novo pCCA. Outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation are similar for patients with PSC-associated pCCA. However, LDLT for de novo pCCA shows a trend toward more disease recurrence and worse patient survival. A period of waiting time before transplant may be beneficial in selecting for patients with superior outcomes after transplant. Compared with liver transplantation for other indications, there is an increased risk of late arterial and portal vein complications, presumably due to the radiation. However, with close follow-up and prompt intervention for vascular complications, graft loss can be avoided. Neoadjuvant therapy and liver transplantation can achieve results comparable with resection for patients with early-stage unresectable pCCA and is the treatment of choice for patients with pCCA arising in the setting of PSC.
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Affiliation(s)
- Ek Khoon Tan
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA
| | - Timucin Taner
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA.,Department of Immunology, Mayo Clinic, Rochester, MN, USA
| | - Julie K Heimbach
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Charles B Rosen
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA.
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30
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Liver Transplantation for Cholangiocarcinoma and Mixed Hepatocellular Cholangiocarcinoma: Working Group Report From the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1125-1130. [PMID: 32217937 DOI: 10.1097/tp.0000000000003212] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver transplantation for cholangiocarcinoma has been an absolute contraindication worldwide due to poor results. However, in recent years and thanks to improvements of patient management and treatments of this cancer, this indication has been revisited. This consensus paper, approved by the International Liver Transplant Society, aims to provide a collection of expert opinions, consensus, and best practices surrounding liver transplantation for cholangiocarcinoma.
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31
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Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, Calvisi DF, Perugorria MJ, Fabris L, Boulter L, Macias RIR, Gaudio E, Alvaro D, Gradilone SA, Strazzabosco M, Marzioni M, Coulouarn C, Fouassier L, Raggi C, Invernizzi P, Mertens JC, Moncsek A, Ilyas SI, Heimbach J, Koerkamp BG, Bruix J, Forner A, Bridgewater J, Valle JW, Gores GJ. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 2020; 17:557-588. [PMID: 32606456 PMCID: PMC7447603 DOI: 10.1038/s41575-020-0310-z] [Citation(s) in RCA: 1457] [Impact Index Per Article: 291.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/29/2020] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
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Affiliation(s)
- Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain.
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
| | - Jose J G Marin
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Shahid A Khan
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Jesper B Andersen
- Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Diego F Calvisi
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
| | - Luca Fabris
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy
- Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA
| | - Luke Boulter
- MRC-Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Rocio I R Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
| | - Eugenio Gaudio
- Division of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Alvaro
- Department of Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | | | - Mario Strazzabosco
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy
- Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA
| | - Marco Marzioni
- Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy
| | | | - Laura Fouassier
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France
| | - Chiara Raggi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center of Autoimmune Liver Diseases, Department of Medicine and Surgery, San Gerardo Hospital, University of Milano, Bicocca, Italy
| | - Joachim C Mertens
- Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zürich, Switzerland
| | - Anja Moncsek
- Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zürich, Switzerland
| | - Sumera I. Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | | | | | - Jordi Bruix
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Alejandro Forner
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
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Hand F, Hoti E. Contemporary role of liver transplantation for the treatment of cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:475-481. [PMID: 32401554 DOI: 10.1080/17474124.2020.1765771] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Cholangiocarcinoma (CCA) is a dismal disease with limited management options. Surgical resection remains the only established treatment however, due to its inherent predilection to invade vascular structures, only a fraction of patients with CCA meet resection criteria at diagnosis. Furthermore, R0 margins, crucial to obtain optimum survival can often prove elusive. AREAS COVERED This review discusses the evolution of liver transplant for CCA, following its introduction in the 1990 s with less than exemplary outcomes. While transplantation is not standard of care, emerging data has suggested a crucial role in prolonging survival of those with CCA. Here we analyze the current role of orthotopic liver transplantation (OLT) in cirrhotic and non-cirrhotic patients, in the setting of both intrahepatic CCA and hilar CCA in order to establish whether this is a judicious use of a precious resource. EXPERT OPINION Liver transplant has a definite role in the treatment of CCA, as highlighted by ongoing clinical trials. A greater understanding of tumor biology coupled with results of current studies will help elucidate which patients will best benefit from OLT. While significant strides are being made to improve outcomes, this must be tempered with an understanding of the finite nature of liver grafts.
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Affiliation(s)
- Fiona Hand
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's, University Hospital , Dublin 4, Ireland
| | - Emir Hoti
- Department of Hepatobiliary and Liver Transplant Surgery, St. Vincent's, University Hospital , Dublin 4, Ireland
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Zen Y, Srinivasan P, Kitagawa M, Suzuki K, Heneghan M, Prachalias A. De novo perihilar cholangiocarcinoma arising in the allograft liver 15 years post-transplantation for biliary atresia. Pathol Int 2020; 70:563-567. [PMID: 32350971 DOI: 10.1111/pin.12944] [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] [Received: 03/02/2020] [Revised: 04/08/2020] [Accepted: 04/13/2020] [Indexed: 12/23/2022]
Abstract
Most primary liver cancers diagnosed in allograft livers are recurrent tumors of the native liver origin, while donor-derived primary liver cancers are markedly less common. A 21-year-old woman who had liver transplantation for post-Kasai biliary atresia was recently referred for post-transplant biliary stricture. Her transplantation was performed at the age of 6 years using the whole liver graft from a 10-year-old donor and choledocho-jejunostomy. The post-transplant course was uneventful in the first 15 years until she presented with obstructive jaundice. The stricture was located at the level of the hepaticojejunostomy, and required percutaneous transhepatic drainage and bile duct dilatation. She underwent an exploratory laparotomy, which suggested a neoplastic process widely involving the extrahepatic and intrahepatic large bile ducts. The histological examination of the resected extrahepatic bile duct confirmed infiltrating moderately differentiated adenocarcinoma. Molecular tests of multiple short tandem repeat loci confirmed the donor origin of the tumor. After four cycles of chemotherapy with gemicitabine and cisplatin, she is currently on radiotherapy in view of potential re-transplantation. De novo, post-transplant cholangiocarcinoma of graft origin is extremely uncommon with only three other cases reported. Two were associated with recurrent primary sclerosing cholangitis, and all had choledocho-jejunostomy at the time of transplantation.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Misa Kitagawa
- Department of Legal Medicine, Osaka Medical College, Osaka, Japan
| | - Koichi Suzuki
- Department of Legal Medicine, Osaka Medical College, Osaka, Japan
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Lee TC, Morris MC, Patel SH, Shah SA. Expanding the Surgical Pool for Hepatic Resection to Treat Biliary and Primary Liver Tumors. Surg Oncol Clin N Am 2019; 28:763-782. [PMID: 31472918 DOI: 10.1016/j.soc.2019.06.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Surgical management of primary liver and biliary tract tumors has evolved over the past several decades, resulting in improved outcomes in these malignancies with historically poor prognoses. Expansion of patient selection criteria, progress in neoadjuvant and adjuvant therapies, development of techniques to increase future liver remnant, and the select utilization of liver transplantation have all contributed to increasing the patient pool for surgical intervention. Ongoing and future studies need to focus on improving multimodality treatment regimens and further refining the selection criteria for transplantation in order to optimize utilization of limited organ resources.
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Affiliation(s)
- Tiffany C Lee
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA
| | - Mackenzie C Morris
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA
| | - Sameer H Patel
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA
| | - Shimul A Shah
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA.
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Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP Rep 2019; 1:377-391. [PMID: 32039389 PMCID: PMC7005652 DOI: 10.1016/j.jhepr.2019.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology.
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Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol 2019; 45:1432-1438. [PMID: 30914290 DOI: 10.1016/j.ejso.2019.03.023] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/01/2019] [Accepted: 03/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear. PATIENTS AND METHODS Using the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model. RESULTS Of the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64-0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group. CONCLUSION In this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.
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Affiliation(s)
| | - Hao Xie
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Irbaz Bin-Riaz
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Prabin Sharma
- Department of Gastroenterology, Yale New Haven Health - Bridgeport Hospital, Bridgeport, CT, 06610, USA
| | - Urshila Durani
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Gaurav Goyal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Bijan Borah
- Robert D. and Patricia E. Kern Mayo Clinic Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Mitesh J Borad
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA
| | | | - Amit Mahipal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
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Bacalbașa N, Balescu I, Vilcu M, Brezean I, Bodog A. Is there a place for liver transplantation in cases with unresectable central cholangiocarcinoma? JOURNAL OF CLINICAL AND INVESTIGATIVE SURGERY 2018. [DOI: 10.25083/2559.5555/3.2/57.61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Central cholangiocarcinoma represents a very aggressive malignancy associated with poor survival rats especially due to the fact that most patients are diagnosed in advanced stages of the disease when curative resection is no longer feasible. In order to try improving the long-term outcomes of these patients, especially in unresectable cases liver transplantation has been proposed with promising results. This is a literature review of the largest studies focused on this subject. Cholangiocarcinomas remain aggressive tumors with poor outcomes whenever surgery with curative intent is not feasible. Currently, the largest experience accumulated consists of neoadjuvant external beam radiotherapy in association with beam radiation, 5 fluorouracil and capecitabine followed by orthotopic liver transplantation. Following this therapeutic protocol excellent long-term outcomes have been reported even if vascular involvement is present.
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Loveday BPT, Knox JJ, Dawson LA, Metser U, Brade A, Horgan AM, Gallinger S, Greig PD, Moulton CA. Neoadjuvant hyperfractionated chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma in Canada. J Surg Oncol 2018; 117:213-219. [PMID: 29480952 DOI: 10.1002/jso.24833] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 08/17/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Neoadjuvant chemoradiation and liver transplantation may be offered for unresectable perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate and survival of patients who entered a national tri-modality protocol. METHOD Patients enrolled Jan 2009-Aug 2015 were included. Enrolment criteria: ≤65 years, brush biopsy-proven unresectable pCCA <3.5 cm diameter. Conformal radiotherapy was given concurrently with Capecitabine. Following surgical staging, patients received maintenance Cisplatin and Gemcitabine until transplant or progression. Time to event analyses were performed from start of neoadjuvant therapy. RESULTS Of 43 patients screened, 18 started treatment; median age 53.9 (26.7-62.8) years, tumour diameter 2.7 (2.0-3.4) cm. 11/18 dropped out due to metastatic disease identified during chemoradiation (n = 2), surgical staging (n = 6), or maintenance chemotherapy (n = 3). Six patients underwent transplantation. Median follow up was 17.6 (4.9-57.7) months and overall survival 16.4 months. One and two year survival was 70.6% and 35.3%, respectively. One and 2 year post transplant survival was 83.3% and 55.6%. Median progression free survival was 11.5 months. CONCLUSION Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although with high rates of dropout and disease progression. Further research is required to determine factors to help select patients for treatment.
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Affiliation(s)
| | - Jennifer J Knox
- Department of Medical Oncology, Princess Margaret Cancer Centre (PMCC), Ontario, Canada.,The University of Toronto, Toronto, Canada
| | - Laura A Dawson
- The University of Toronto, Toronto, Canada.,Department of Radiation Oncology, Princess Margaret Cancer Centr (PMCC), Ontario, Canada
| | - Ur Metser
- The University of Toronto, Toronto, Canada.,Joint Department of Medical Imaging, Toronto General Hospital, Ontario, Canada
| | - Anthony Brade
- The University of Toronto, Toronto, Canada.,Department of Radiation Oncology, Princess Margaret Cancer Centr (PMCC), Ontario, Canada
| | - Anne M Horgan
- Department of Medical Oncology, Princess Margaret Cancer Centre (PMCC), Ontario, Canada.,The University of Toronto, Toronto, Canada
| | - Steven Gallinger
- Department of Surgery, Toronto General Hospital, Ontario, Canada.,The University of Toronto, Toronto, Canada
| | - Paul D Greig
- Department of Surgery, Toronto General Hospital, Ontario, Canada.,The University of Toronto, Toronto, Canada
| | - Carol-Anne Moulton
- Department of Surgery, Toronto General Hospital, Ontario, Canada.,The University of Toronto, Toronto, Canada
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40
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Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma. Liver Transpl 2018; 24:294-303. [PMID: 29024405 DOI: 10.1002/lt.24955] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/06/2017] [Accepted: 10/01/2017] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma (CCA) is the second most common liver cancer, and it is associated with a poor prognosis. CCA can be divided into intrahepatic, hilar, and distal. Despite the subtype, the median survival is 12-24 months without treatment. Liver transplantation (LT) is recognized worldwide as a curative option for hepatocellular carcinoma. On the other hand, the initial results for LT for CCA were very poor mainly due to a lack of adequate patient selection. In the last 2 decades, improvements have been made in the management of unresectable hilar CCA, and the results of LT after neoadjuvant chemoradiation have been shown to be promising. This has prompted a consideration of hilar CCA as an indication for LT in some centers. Furthermore, some recent research has shown promising results after LT for patients with early stages of intrahepatic CCA. A better understanding of the best tools to prognosticate the outcomes of LT for CCA is still needed. Here, we aimed to review the role of LT for the treatment of patients with perihilar and intrahepatic CCA. Also, we will discuss the most recent advances in the field and the future direction of the management of this disease in an era of transplantation oncology. Liver Transplantation 24 294-303 2018 AASLD.
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Affiliation(s)
- Nicolás Goldaracena
- Multi-Organ Transplant, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Andre Gorgen
- Multi-Organ Transplant, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
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41
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Schaefer B, Zoller H, Schneeberger S. Con: Liver transplantation for expanded criteria malignant diseases. Liver Transpl 2018; 24:104-111. [PMID: 29125687 DOI: 10.1002/lt.24975] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 10/04/2017] [Indexed: 12/18/2022]
Abstract
Organ shortage requires policies and guidelines to aid organ allocation along the principles of urgency or utility. Identifying patients with significant benefit and withholding liver transplantation (LT) from patients too sick for transplantation are ongoing challenges, in particular in patients with malignancies. An arbitrary threshold of >50% 5-year overall survival (OS) is broadly considered a minimum standard for LT. In patients transplanted for intrahepatic cholangiocarcinoma (iCC), this was only achieved in select cases and when the tumor had a diameter of <2 cm. In patients with extrahepatic and hilar cholangiocarcinoma (CCC), strict selection criteria and combined preoperative radiotherapy/chemotherapy according to the Mayo protocol showed that acceptable longterm results can be achieved in a single high-volume center but are difficult to repeat elsewhere. Furthermore, only rigorously selected patients with neuroendocrine tumors (NETs) meeting the NET Milan criteria adopted by United Network for Organ Sharing can also have >50% 5-year OS. A prospective study in patients with unresectable colorectal cancer metastases in the liver has shown promising OS rates, but further prospective trials are warranted. Current evidence shows that none of the proposed expanded malignant criteria justify deviation of scarce donor organs to patients with hilar CCC, iCC > 2 cm, metastatic NET beyond NET Milan criteria, or metastatic colorectal cancer (CRC) outside clinical trials. Liver Transplantation 24 104-111 2018 AASLD.
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Affiliation(s)
- Benedikt Schaefer
- Divisions of Gastroenterology, Hepatology and Endocrinology, Department of Internal Medicine I
| | - Heinz Zoller
- Divisions of Gastroenterology, Hepatology and Endocrinology, Department of Internal Medicine I
| | - Stefan Schneeberger
- Visceral, Transplant and Thoracic Surgery, Department of Surgery, Medical University of Innsbruck, Innsbruck, Austria
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Riechelmann R, Coutinho AK, Weschenfelder RF, Andrade DE Paulo G, Fernandes GDS, Gifoni M, Oliveira MDL, Gansl R, Gil R, Luersen G, Lucas L, Reisner M, Vieira FM, Machado MA, Murad A, Osvaldt A, Brandão M, Carvalho E, Souza T, Pfiffer T, Prolla G. GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP. ARQUIVOS DE GASTROENTEROLOGIA 2017; 53:5-9. [PMID: 27276097 DOI: 10.1590/s0004-28032016000100003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 09/22/2015] [Indexed: 02/06/2023]
Abstract
The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.
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Affiliation(s)
- Rachel Riechelmann
- Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil, Instituto do Câncer do Estado de São Paulo, São Paulo SP , Brasil.,Hospital Sírio Libanês, São Paulo, SP, Brasil, Hospital Sírio-Libanês, Hospital Sírio Libanês, São Paulo SP , Brazil
| | | | - Rui F Weschenfelder
- Hospital Moinhos de Vento, Porto Alegre, RS, Brasil, Hospital Moinhos de Vento, Hospital Moinhos de Vento, Porto Alegre RS , Brazil
| | - Gustavo Andrade DE Paulo
- Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil, Instituto do Câncer do Estado de São Paulo, São Paulo SP , Brasil
| | - Gustavo Dos Santos Fernandes
- Oncologia, Hospital Sírio Libanês, Brasília, DF, Brasil, Hospital Sírio-Libanês, Hospital Sírio Libanês, Brasília DF , Brazil
| | - Markus Gifoni
- Clínica Fujiday Oncologia, Fortaleza, CE, Brasil, Clínica Fujiday Oncologia, Fortaleza CE , Brasil
| | | | - Rene Gansl
- Centro Paulista de Oncologia, São Paulo, SP, Brasil, Centro Paulista de Oncologia, São Paulo SP , Brasil
| | - Roberto Gil
- Instituto Nacional do Câncer, Rio de Janeiro, RJ, Brasil, Instituto Nacional do Câncer, Instituto Nacional do Câncer, Rio de Janeiro RJ , Brazil
| | - Gustavo Luersen
- Hospital Moinhos de Vento, Porto Alegre, RS, Brasil, Hospital Moinhos de Vento, Hospital Moinhos de Vento, Porto Alegre RS , Brazil
| | - Lucio Lucas
- Hospital de Base, Brasília, DF, Brasil, Hospital de Base, Brasília DF , Brasil
| | - Marcio Reisner
- Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, Universidade Federal do Rio de Janeiro, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ , Brazil
| | - Fernando Meton Vieira
- Instituto COI de Pesquisa, Educação e Gestão, Rio de Janeiro, RJ, Brasil, Instituto COI de Pesquisa, Educação e Gestão, Rio de Janeiro RJ , Brasil
| | - Marcel Autran Machado
- Hospital Sírio Libanês, São Paulo, SP, Brasil, Hospital Sírio-Libanês, Hospital Sírio Libanês, São Paulo SP , Brazil
| | - Andre Murad
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil, Universidade Federal de Minas Gerais, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte MG , Brazil
| | - Alessandro Osvaldt
- Hospital de Clínicas, Porto Alegre, RS, Brasil, Hospital de Clínicas, Porto Alegre RS , Brasil
| | - Miguel Brandão
- Clínica AMO, Salvador, BA, Brasil, Clínica AMO, Salvador BA , Brasil
| | - Elisangela Carvalho
- Hospital Português, Salvador, BA, Brasil, Hospital Português, Hospital Português, Salvador BA , Brazil
| | - Tulio Souza
- Hospital Aliança, Salvador, BA, Brasil, Hospital Aliança, Salvador BA , Brasil
| | - Tulio Pfiffer
- Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil, Instituto do Câncer do Estado de São Paulo, São Paulo SP , Brasil
| | - Gabriel Prolla
- Hospital Mãe de Deus, Porto Alegre, RS, Brasil, Hospital Mãe de Deus, Hospital Mãe de Deus, Porto Alegre RS , Brazil
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43
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Iqbal M, Elrayah EA, Traynor O, McCormick PA. Liver transplantation in Ireland. Liver Transpl 2016; 22:1014-8. [PMID: 27065358 DOI: 10.1002/lt.24456] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 03/14/2016] [Indexed: 02/07/2023]
Abstract
The Irish National Liver Transplant program commenced in 1993 in St. Vincent's University Hospital in Dublin. It is an adult-only program and is the only liver transplant program in Ireland. Pediatric recipients are referred to King's College Hospital in the United Kingdom. To date, almost 1000 adult liver transplants have been performed. Current 1-year patient survival is 93%, and 5-year survival is 79%. The program is fully funded by the government health service. There is a close collaboration with the United Kingdom Organ Donation and Transplant Directorate, and there is an arrangement for organ sharing for super-urgent transplants. Traditionally, organ donation rates have been high in Ireland. However, demand for liver transplant has increased over the past 20 years, and waiting lists are now lengthening. Deceased cardiac death donation is now being considered, but there are no plans for living related donor liver transplant. Donor coordinators have recently been appointed to the major hospitals in Ireland, and it is hoped that this initiative will lead to an increase in organ donation rates. Liver Transplantation 22 1014-1018 2016 AASLD.
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Affiliation(s)
- Masood Iqbal
- Liver Unit, St. Vincent's University Hospital, Dublin, Ireland
| | | | - Oscar Traynor
- Liver Unit, St. Vincent's University Hospital, Dublin, Ireland.,The Royal College of Surgeons in Ireland, Dublin, Ireland
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Mantel HTJ, Westerkamp AC, Adam R, Bennet WF, Seehofer D, Settmacher U, Sánchez-Bueno F, Fabregat Prous J, Boleslawski E, Friman S, Porte RJ. Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival. PLoS One 2016; 11:e0156127. [PMID: 27276221 PMCID: PMC4898828 DOI: 10.1371/journal.pone.0156127] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 05/10/2016] [Indexed: 12/17/2022] Open
Abstract
Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience.
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Affiliation(s)
- Hendrik T. J. Mantel
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Andrie C. Westerkamp
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - René Adam
- Department of Hepatobiliary Surgery, Hôpital Paul Brousse, University of Paris-Sud, Villejuif, France
| | - William F. Bennet
- Transplant Institute, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Daniel Seehofer
- Department of General, Visceral and Transplantation Surgery, Charité Campus Virchow, Berlin, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University of Jena, Jena, Germany
| | - Francisco Sánchez-Bueno
- Department of Surgery and Liver and Pancreas Transplantation, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Joan Fabregat Prous
- Department of Hepato-Pancreatico- Biliary Surgery and Liver Transplantation, University Hospital de Bellvitge, University of Barcelona, Barcelona, Spain
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, Lille University Medical Center, University of Lille Nord de France, Lille, France
| | - Styrbjörn Friman
- Transplant Institute, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Robert J. Porte
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- * E-mail:
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Liver transplantation for hepatobiliary malignancies: a new era of "Transplant Oncology" has begun. Surg Today 2016; 47:403-415. [PMID: 27130463 DOI: 10.1007/s00595-016-1337-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 04/06/2016] [Indexed: 01/10/2023]
Abstract
The indications of liver transplantation for hepatobiliary malignancies have been carefully expanded in a stepwise fashion, despite the fundamental limitations in oncological, immunological, and technical aspects. A new era of "Transplant Oncology," the fusion of transplant surgery and surgical oncology, has begun, and we stand at the dawn of a paradigm shift in multidisciplinary cancer treatment. For hepatocellular carcinoma, new strategies have been undertaken to select recipients based on biological and dynamic markers instead of conventional morphological and static parameters, opening the doors for a more deliberate expansion of the Milan criteria and locoregional therapies before liver transplantation. Neoadjuvant chemoradiation therapy followed by liver transplantation for unresectable perihilar cholangiocarcinoma developed by the Mayo Clinic provided excellent outcomes in a US multicenter study; however, the surgical indications are not necessarily universal and await international validation. Similarly, an aggressive multidisciplinary approach has been applied for other tumors, including intrahepatic cholangiocarcinoma, hepatoblastoma, liver metastases from colorectal and neuroendocrine primary and gastrointestinal stromal tumors as well as rare tumors, such as hepatic undifferentiated embryonal sarcoma and infantile choriocarcinoma. In conclusion, liver transplantation is an important option for hepatobiliary malignancies; however, prospective studies are urgently needed to ensure the appropriate patient selection, organ allocation and living donation policies, and administration of antineoplastic immunosuppression.
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Marchan EM, Landry JC. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience. J Gastrointest Oncol 2016; 7:248-54. [PMID: 27034793 DOI: 10.3978/j.issn.2078-6891.2015.117] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. METHODS Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium(192) (Ir(192)) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. RESULTS Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest interval (37 months). Post OLT mortality resulted from (I) unknown causes (0.5 months), (II) allograft rejection (27.25 months). Other toxicities included: necrotic myelitis 12/10 months after NEO/OLT (n=1), post NEO biliary stricture requiring new stent (n=1); post Whipple bile leak repair (n=1), and post OLT fistula (n=1), cholangitis (n=1), and wound revision (n=2). CONCLUSIONS Our outcomes using NEO-OLT for CCA are promising and comparable to other series. These results further justify (I) use of NEO and (II) prioritization of available transplant livers for CCA management.
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Affiliation(s)
- Edward M Marchan
- 1 Department of Radiation Oncology, GRU Cancer Center, Georgia Regents University, Augusta, GA 30912, USA ; 2 Emory University School of Medicine/Radiation Oncology, Atlanta, GA 30322, USA
| | - Jerome C Landry
- 1 Department of Radiation Oncology, GRU Cancer Center, Georgia Regents University, Augusta, GA 30912, USA ; 2 Emory University School of Medicine/Radiation Oncology, Atlanta, GA 30322, USA
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Burkhart RA, Laheru DA, Herman JM, Pawlik TM. Multidisciplinary management and the future of treatment in cholangiocarcinoma. Expert Opin Orphan Drugs 2016. [DOI: 10.1517/21678707.2016.1130618] [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] [Indexed: 01/04/2023]
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Nayagam JS, Pereira SP, Devlin J, Harrison PM, Joshi D. Controversies in the management of primary sclerosing cholangitis. World J Hepatol 2016; 8:265-272. [PMID: 26925200 PMCID: PMC4757649 DOI: 10.4254/wjh.v8.i5.265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Revised: 10/13/2015] [Accepted: 01/22/2016] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) remains a rare but significant disease, which affects mainly young males in association with inflammatory bowel disease. There have been few advances in the understanding of the pathogenesis of the condition and no therapeutics with proven mortality benefit aside from liver transplantation. There remain areas of controversy in the management of PSC which include the differentiation from other cholangiopathies, in particular immunoglobulin G4 related sclerosing cholangitis, the management of dominant biliary strictures, and the role of ursodeoxycholic acid. In addition, the timing of liver transplantation in PSC remains difficult to predict with standard liver severity scores. In this review, we address these controversies and highlight the latest evidence base in the management of PSC.
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Lai Q, Lerut J. Proposal for an algorithm for liver transplantation in Caroli's disease and syndrome: putting an uncommon effort into a common task. Clin Transplant 2016; 30:3-9. [PMID: 26385435 DOI: 10.1111/ctr.12640] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2015] [Indexed: 12/12/2022]
Abstract
Liver transplantation (LT) represents an uncommon indication for Caroli's disease (CD) or syndrome (CS). Excellent results of LT have been reported as shown by recent multicentric European and American registry reports. Clear therapeutic flowcharts to adopt in these diseases are still lacking. This review aims at analyzing highlighting recent transplant experiences in this field and also at focusing on the role of LT in case-specific comorbidities such as development of cholangiocellular cancer or renal failure are present.
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Affiliation(s)
- Quirino Lai
- Starzl Unit Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, UCL, Brussels, Belgium
- Transplant Unit, Department of Surgery, University of L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Jan Lerut
- Starzl Unit Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, UCL, Brussels, Belgium
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Gulamhusein AF, Sanchez W. Liver transplantation in the management of perihilar cholangiocarcinoma. Hepat Oncol 2015; 2:409-421. [PMID: 30191020 DOI: 10.2217/hep.15.30] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common primary hepatic neoplasm and accounts for 10-20% of hepatobiliary cancer-related deaths. The prognosis of patients with CCA is poor with 5-year survival rates of 10%, partially due to the limited effective treatment options that exist for this disease. In this review, we discuss the evolving role of liver transplantation in the management of patients with perihilar CCA (pCCA). We specifically discuss the Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation in selected patients with pCCA and describe pretransplant, peritransplant, and post-transplant considerations and challenges with this approach. Finally, we review local, national and international outcomes and discuss future directions in optimizing this treatment strategy for patients who otherwise have few therapeutic options and limited survival.
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Affiliation(s)
- Aliya F Gulamhusein
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - William Sanchez
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
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