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1
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Arora A, Sharma P, Kumar A, Acharya S, Sarin SK, Duseja A, Puri P, Shah S, Chawla Y, Rao P, Saraya A, Mohanka R, Singh S, Saighal S, Rela M, Vij V, Asthana S, Shukla A, Bhangui P, Saraf N, Maiwall R, Mandot A, Saraswat V, Madan K, Shalimar, Kapoor D, Anand AC, Gupta S, Varghese J, Mehta N. Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation. J Clin Exp Hepatol 2025; 15:102539. [PMID: 40343081 PMCID: PMC12056968 DOI: 10.1016/j.jceh.2025.102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 02/24/2025] [Indexed: 05/10/2025] Open
Abstract
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - S.K. Acharya
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Ajay Duseja
- Post Institute of Medical Sciences, Chandigarh, India
| | | | - Samir Shah
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Y.K. Chawla
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - P.N. Rao
- Asian Institute of Gsstroenterology, Hyderabad, India
| | - Anoop Saraya
- All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Mumbai, India
| | | | | | - Mohamed Rela
- Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Vivek Vij
- Fortis Hospital, Noida, Delhi, India
| | - Sonal Asthana
- Aster CMI Bangalore, Aster RV Bangalore, Aster Whitefield, Bangalore, India
| | - Akash Shukla
- Reliance Foundation Hospital and Research Centre, Mumbai, India
- Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | | | | | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Amit Mandot
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | | | | | - Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Dharmesh Kapoor
- Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
- Yashoda Hospital, Hyderabad, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | | | - Joy Varghese
- Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Naimish Mehta
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
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Ciria R, Ivanics T, Aliseda D, Claasen M, Alconchel F, Gaviria F, Briceño J, Berardi G, Rotellar F, Sapisochin G. Liver transplantation for primary and secondary liver tumors: Patient-level meta-analyses compared to UNOS conventional indications. Hepatology 2025; 81:1700-1713. [PMID: 39465987 DOI: 10.1097/hep.0000000000001129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 08/26/2024] [Indexed: 10/29/2024]
Abstract
BACKGROUND AND AIMS Liver transplant (LT) for transplant oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns about mid-long-term survival and its impact on the waiting list. APPROACH AND RESULTS We conducted 4 systematic reviews of all series on TO indications (intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma [phCC]) and liver metastases from neuroendocrine tumors (NETs) and colorectal cancer (CRLM) and compared them using patient-level meta-analyses to data obtained from the United Network for Organ Sharing (UNOS) database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan criteria for NET). A total of 112,014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494, and 103 patients obtained from meta-analyses on intrahepatic cholangiocarcinoma and phCC, and liver metastases from NET and CRLM, respectively. Five-year overall survival was 53.3%, 56.4%, 68.6%, and 53.8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second, and third LT and not statistically significantly different from LT in recipients >70 years and high BMI. CONCLUSIONS Liver transplantation for TO indications has adequate 5-year survival rates, mostly when performed under the selection criteria available in the literature (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan for NET). Despite concerns about its impact on the waiting list, some other LT indications are being performed with lower survival rates. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria.
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Affiliation(s)
- Ruben Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, University of Cordoba, IMIBIC, Cordoba, Spain
- Unit of Hepatobiliary Surgery, Hospital Quiron Salud, Cordoba, Spain
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, Michigan, USA
- Department of Surgical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden
| | - Daniel Aliseda
- Hepatobiliary Surgery and Liver Transplant Unit, Clinica Universidad de Navarra, Pamplona, Spain
- Institute of Health Research of Navarra (IdisNA), Pamplona, Spain
| | - Marco Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Felipe Alconchel
- Unit of Hepatobiliary Surgery and Liver Transplantation, Hospital Clínico Universitario Virgen Arrixaca, University of Medicine, IMIB-Pascual Parrilla, Murcia, Spain
| | - Felipe Gaviria
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Javier Briceño
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, University of Cordoba, IMIBIC, Cordoba, Spain
| | - Giammauro Berardi
- General Surgery and Organ Transplantation Unit, San Camillo-Forlanini Hospital, Rome, Italy
| | - Fernando Rotellar
- Hepatobiliary Surgery and Liver Transplant Unit, Clinica Universidad de Navarra, Pamplona, Spain
- Institute of Health Research of Navarra (IdisNA), Pamplona, Spain
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
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Kasai Y, Ito T, Masui T, Nagai K, Anazawa T, Uchida Y, Ishii T, Umeshita K, Eguchi S, Soejima Y, Ohdan H, Hatano E. Liver transplantation for gastroenteropancreatic neuroendocrine liver metastasis: optimal patient selection and perioperative management in the era of multimodal treatments. J Gastroenterol 2025; 60:1-9. [PMID: 39547997 PMCID: PMC11717855 DOI: 10.1007/s00535-024-02166-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 10/25/2024] [Indexed: 11/17/2024]
Abstract
Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6 months before LT; (5) age ≤ 55 years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments.
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Affiliation(s)
- Yosuke Kasai
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takashi Ito
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
- Department of Surgery, Kurashiki Central Hospital, Okayama, Japan
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yoichiro Uchida
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Koji Umeshita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
- Osaka International Cancer Institute, Osaka, Japan
| | - Susumu Eguchi
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Yuji Soejima
- Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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4
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Lai Q, Coppola A, Mrzljak A, Cigrovski Berkovic M. Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence. Biomedicines 2024; 12:2419. [PMID: 39594986 PMCID: PMC11592406 DOI: 10.3390/biomedicines12112419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/14/2024] [Accepted: 10/16/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients. METHODS The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence. RESULTS LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age. CONCLUSIONS Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, 00161 Rome, Italy;
| | - Alessandro Coppola
- Department of General Surgery, Sapienza University of Rome, 00161 Rome, Italy;
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, 10000 Zagreb, Croatia;
- University of Zagreb, Department of Medicine, School of Medicine, 10000 Zagreb, Croatia
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Melehy A, Agopian V. Treating rare tumors with liver transplantation. Curr Opin Organ Transplant 2024; 29:30-36. [PMID: 37851086 DOI: 10.1097/mot.0000000000001118] [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: 10/19/2023]
Abstract
PURPOSE OF REVIEW The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS). RECENT FINDINGS Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines. SUMMARY GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
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Affiliation(s)
- Andrew Melehy
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California, USA
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7
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Gorji L, Brown ZJ, Limkemann A, Schenk AD, Pawlik TM. Liver Transplant as a Treatment of Primary and Secondary Liver Neoplasms. JAMA Surg 2024; 159:211-218. [PMID: 38055245 DOI: 10.1001/jamasurg.2023.6083] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023]
Abstract
Importance Liver malignancies are an increasing global health concern with a high mortality. We review outcomes following liver transplant for primary and secondary hepatic malignancies. Observations Transplant may be a suitable treatment option for primary and secondary hepatic malignancies in well-selected patient populations. Conclusions and Relevance Many patients with primary or secondary liver tumors are not eligible for liver resection because of advanced underlying liver disease or high tumor burden, precluding complete tumor clearance. Although liver transplant has been a long-standing treatment modality for patients with hepatocellular carcinoma, recently transplant has been considered for patients with other malignant diagnoses. In particular, while well-established for hepatocellular carcinoma and select patients with perihilar cholangiocarcinoma, transplant has been increasingly used to treat patients with intrahepatic cholangiocarcinoma, as well as metastatic disease from colorectal liver and neuroendocrine primary tumors. Because of the limited availability of grafts and the number of patients on the waiting list, optimal selection criteria must be further defined. The ethics of organ allocation to individuals who may benefit from prolonged survival after transplant yet have a high incidence of recurrence, as well as the role of living donation, need to be further discerned in the setting of transplant oncology.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, Ohio
| | - Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, New York University-Long Island, Mineola
| | - Ashley Limkemann
- Division of Transplant, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
| | - Austin D Schenk
- Division of Transplant, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, James Cancer Hospital, Columbus
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8
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Krendl FJ, Bellotti R, Sapisochin G, Schaefer B, Tilg H, Scheidl S, Margreiter C, Schneeberger S, Oberhuber R, Maglione M. Transplant oncology - Current indications and strategies to advance the field. JHEP Rep 2024; 6:100965. [PMID: 38304238 PMCID: PMC10832300 DOI: 10.1016/j.jhepr.2023.100965] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/31/2023] [Accepted: 11/04/2023] [Indexed: 02/03/2024] Open
Abstract
Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.
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Affiliation(s)
- Felix J. Krendl
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Benedikt Schaefer
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Austria
| | - Herbert Tilg
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Austria
| | - Stefan Scheidl
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Austria
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9
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Liu Y, Wang Z, Lin Q, Cui R, Tang W, Li G, Wang Z. Resection of the primary tumor improves the prognosis of gastrointestinal neuroendocrine neoplasms with liver metastases: mutual validation based on SEER database and institutional data. BMC Gastroenterol 2023; 23:408. [PMID: 37993767 PMCID: PMC10666352 DOI: 10.1186/s12876-023-03041-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 11/08/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND Gastrointestinal Neuroendocrine Neoplasms (GI-NENs) often result in liver metastases, and the role of Primary Tumor Resection (PTR) in managing GI-NENs with liver metastases (GI-NENLM) is still debated. This study aimed to investigate the potential benefits of PTR in treating GI-NENLM by analyzing data from the Surveillance, Epidemiology, and End Results Program (SEER) and the First Affiliated Hospital of Sun Yat-sen University (FAH). METHODS The SEER Registry 17 database and the FAH clinical pathology database were used to collect clinicopathology data for GI-NENLM diagnosed between 2010 and 2019 and between 2011 and 2022, respectively. Propensity score matching (PSM) was used to match the clinicopathological characteristics of patients from both cohorts. Inverse probability weighting (IPTW) was used to weigh the PTR and non-PTR groups. The primary endpoint was overall survival (OS). RESULTS After matching, 155 patients from the SEER database were matched to the FAH cohort. PTR was significantly associated with better prognosis in PSM-matched/unmatched SEER cohorts (P < 0.01) and in the FAH cohort even after eliminating selection bias using IPTW (p < 0.01). Subgroup analysis suggests that the cohort consisting of patients aged 55 years or older, individuals with colorectal primary tumors, those at the T1 disease stage, and those without extrahepatic metastasis may potentially benefit from PTR. Interaction analysis showed no significant interaction between PTR and other clinical and pathological factors except for age. CONCLUSION The employment of PTR in patients with GI-NENLM is significantly correlated with individual survival benefits. We support performing PTR on carefully evaluated patients.
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Affiliation(s)
- Yifan Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China
| | - Qi Lin
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China
| | - Ruizhe Cui
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China
| | - Wei Tang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China
| | - Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China.
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, 510080, Guangzhou, 86, Guangdong, China.
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10
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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11
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Citterio D, Coppa J, Sposito C, Busset MDD, Virdis M, Pezzoli I, Mazzaferro V. The Role of Liver Transplantation in the Treatment of Liver Metastases from Neuroendocrine Tumors. Curr Treat Options Oncol 2023; 24:1651-1665. [PMID: 37882889 PMCID: PMC10643461 DOI: 10.1007/s11864-023-01124-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2023] [Indexed: 10/27/2023]
Abstract
OPINION STATEMENT Transplant oncology is a new field of medicine referred to the use of solid organ transplantation, particularly the liver, to improve prognosis and quality of life in cancer patients. In unresectable, liver-only metastases from neuroendocrine tumors (NETs) of the digestive tract, liver transplantation represents a competitive chance of cure. Due to the limited resource of donated organs, accurate patients' selection is crucial in order to maximize transplant benefit. Several tumor- and patient-related factors should be considered. Among them, primary tumors with a low grade of differentiation (G1-G2 or Ki67 < 10%), located in a region drained by the portal system and removed before transplantation with at least 3-6 months period of disease stability observed before transplant listing, can be considered for transplantation. In case of NET located in the pancreas, extended lymphadenectomy should complement curative pancreatic resection. A number of other features are described in this review of liver transplantation for NET metastases. Comprehensive approach including various forms of non-surgical treatment and detailed planning and timing of total hepatectomy are discussed. Open issues remain on possible expansion of current criteria while maintaining the same long-term benefit demonstrated with the Milan NET criteria with respect to other non-transplant options, with particular reference to liver resection, peptide receptor radionuclide therapy, and locoregional and systemic treatments.
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Affiliation(s)
- Davide Citterio
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Jorgelina Coppa
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Carlo Sposito
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Michele Droz Dit Busset
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Matteo Virdis
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Isabella Pezzoli
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
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12
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Palaniappan V, Li CH, Frilling A, Clift AK. Long-Term Outcomes of Liver Transplantation for the Management of Neuroendocrine Neoplasms: A Systematic Review. J Pers Med 2023; 13:1428. [PMID: 37888039 PMCID: PMC10607978 DOI: 10.3390/jpm13101428] [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: 08/18/2023] [Revised: 09/18/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023] Open
Abstract
Liver transplantation is an uncommonly used, controversially debated therapeutic approach for highly selected individuals with neuroendocrine liver metastases. Synthesising evidence regarding outcomes from this approach is crucial to understand its position within the broad neuroendocrine liver metastases armamentarium. In this narrative systematic review of studies published in PubMed, Scopus and OVID until 1 July 2021, we summarise and critically appraise the existing literature regarding this modality, with a special focus on long-term outcomes data where possible. Fourteen studies were identified that reported outcomes from the use of liver transplantation for metastatic neuroendocrine neoplasms. No randomised trials were identified. Generally, indications and selection criteria were poorly articulated, with the notable exception of studies using the Milan criteria. The median 5-year overall survival was 65% (ranging from 36% to 97.2%, 11 studies), and the median 10-year overall survival was 50% (ranging from 46.1% to 88.8%, 3 studies). One additional study focussed on treatments and outcomes following post-transplant recurrence. No studies reported outcomes past 10 years. Further follow-up of the largest series with explicit selection criteria will deepen our understanding of the role that transplantation has to play in this setting.
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Affiliation(s)
| | - Chun Hei Li
- St George’s University Hospitals NHS Foundation Trust, London SW17 0QT, UK
| | - Andrea Frilling
- Department of Surgery & Cancer, Imperial College London, London SW7 2BX, UK
| | - Ashley Kieran Clift
- Department of Surgery & Cancer, Imperial College London, London SW7 2BX, UK
- Cancer Research UK Oxford Centre, University of Oxford, Oxford OX1 2JD, UK
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13
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Moradi A, Lamsehchi N, Khaki S, Nasiri-Toosi M, Jafarian A. Liver Transplant for Patients With Neuroendocrine Tumor: A Report of 2 Exceptional Cases and Literature Review. EXP CLIN TRANSPLANT 2023; 21:578-585. [PMID: 37584538 DOI: 10.6002/ect.2023.0110] [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: 08/17/2023]
Abstract
Patients with neuroendocrine tumors with unresec-table liver involvement can benefit from liver transplant. There is a specific set of guidelines for neuroendocrine tumors with liver metastasis that involve less than 50% of the liver. However, beyond those guidelines, there are reports of exceptional criteria patients who benefited from liver transplant. Here, we present 2 unusual cases of patients with exceptional circumstances and with neuroendocrine tumors who underwent liver transplant. The first case describes a patient with an extremely rare neuroen-docrine tumor of the proximal common bile duct that caused liver biliary cirrhosis. The patient underwent tumor resection and liver transplant concurrently. The second case describes a patient with a neuroendocrine tumor of unknown primary origin with more than 50% hepatic involvement who received a liver transplant after downstaging. In our center, patients with unresectable hepatic metastases from neuroendoc-rine tumors are currently selected for liver transplant based on well-established criteria. However, these 2 cases did not meet the criteria for consideration of liver transplant; thus, multidisciplinary team sessions were held to discuss these 2 cases. After a period of nonsurgical treatment and evaluation of the tumor behavior, we selected the patients as candidates for liver transplant based on the favorable tumor behavior and favorable response to treatment. For both patients, we did not observe any signs of tumor recurrence during follow-up. The outcomes were acceptable, and the patients tolerated treatment well. Considering the favorable tumor pathology (G1 phase and low Ki67 index), we suggest that more studies should be conducted to evaluate the outcomes of patients with low-grade tumors and that the criteria for patients with low-grade tumors could be extended based on such future data.
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Affiliation(s)
- Alimohammad Moradi
- From the Department of General Surgery Division of Hepato-Pancreatico-Biliary Surgery and Organ Transplantation Surgery, Tehran University of Medical Sciences, Tehran, Iran
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14
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Pancreaticoduodenectomy After Liver Transplantation: A Single-Center Experience. World J Surg 2023; 47:1018-1022. [PMID: 36637476 DOI: 10.1007/s00268-022-06887-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND The aim of this study is to report the feasibility and short-term outcomes of pancreaticoduodenectomy (PD) in patients who have undergone orthotopic liver transplantation (OLT). METHODS We performed a retrospective review of a prospectively maintained pancreatic surgical database for all patients undergoing pancreaticoduodenectomy (PD) after liver transplant from January 1995 until June 2022. Demographics, indications for pancreatic resection, liver transplant and time from liver transplant to PD were reported. Operative mortality and morbidity were recorded within 90 days of surgery. Continuous variables were recorded as mean and range, while categorical variables were summarized using frequency and percentage. Postoperative complications within 90 days from PD were graded based on Clavien-Dindo classification with major complication recorded as grade IIIa or higher. Additionally, a comprehensive literature review was performed. RESULTS A total of 916 patients who underwent PD at our institution between January 1995 and June 2022 were identified, and 9 patients had previous OLT. Five patients were females and 4 males with a mean age of 65 years (range 51-78). Average body mass index (BMI) was 30.8. Two patients had major complications, and three patients had minor complications. No clinically relevant POPF, PPH or DGE were observed. One patient died within 90 days from PD due to ischemic biliary pancreatic limb causing intrabdominal sepsis. CONCLUSION Although uncommon, PD after OLT is feasible with acceptable outcomes at high volume institutions and if performed by experienced surgeons.
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15
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Fernandes EDSM, Kyt CVG, de Mello FPT, Pimentel LS, Andrade RDO, Girão C, César C, Siqueira M, Monachesi ME, Brito A, Tavares de Sousa CC, Andraus W, Torres OJM. Liver transplantation in gastroenteropancreatic neuroendocrine tumors. Front Oncol 2023; 12:1001163. [PMID: 36844922 PMCID: PMC9947829 DOI: 10.3389/fonc.2022.1001163] [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: 07/22/2022] [Accepted: 12/21/2022] [Indexed: 02/11/2023] Open
Abstract
Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.
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Affiliation(s)
- Eduardo de Souza M. Fernandes
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil,Department of Surgery, Rio de Janeiro Federal University, Rio de Janeiro, RJ, Brazil,Department of Hepatology, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,*Correspondence: Eduardo de Souza M. Fernandes,
| | - Camila V. Garcia Kyt
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Felipe Pedreira Tavares de Mello
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Leandro Savattone Pimentel
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Ronaldo de Oliveira Andrade
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Camila Girão
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Camilla César
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Munique Siqueira
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Maria Eduarda Monachesi
- Department of Gastrointestinal and Transplant Surgery, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil,Department of Gastrointestinal and Transplant Surgery, Adventista Silvestre Hospital, Rio de Janeiro, RJ, Brazil
| | - Anderson Brito
- Department of Hepatology, São Lucas-Rede Dasa Hospital, Rio de Janeiro, RJ, Brazil
| | | | - Wellington Andraus
- Department of Gastroenterology, Gastrointestinal and Transplant, São Paulo University Hospital, São Paulo, SP, Brazil
| | - Orlando Jorge M. Torres
- Department of Hepatopancreatobiliary Surgery, Hospital São Domingos-Rede Dasa Hospital, São Luís, MA, Brazil,Department of Gastrointestinal and Transplant Surgery, Hospital Presidente Dutra, São Luis, MA, Brazil
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16
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Kjaer J, Smith S, Hellman P, Stålberg P, Crona J, Welin S, Norlén O. Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation. World J Surg 2023; 47:340-347. [PMID: 36175647 PMCID: PMC9803729 DOI: 10.1007/s00268-022-06736-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND The use of liver transplantation (LT) in patients with stage IV neuroendocrine pancreatic tumors (pan-NET) is under debate. Previous studies report a 5-year survival of 27-53% after LT in pan-NET and up to 92.7% in patients with mixed NETs. This study aimed to determine survival rates of patients with stage IV pan-NET meeting criteria for LT while only subjected to multimodal treatment. METHODS Medical records of patients with pan-NET diagnosed from 2000 to 2021 at a tertiary referral center were evaluated for eligibility. Patients without liver metastases, who did not undergo primary tumor surgery, age > 75 years and with grade 3 tumors were excluded. The patients were divided into groups; all included patients, patients meeting the Milan, the United Network for Organ Sharing (UNOS) or the European Neuroendocrine Tumor Society (ENETS) criteria for LT. Kaplan-Meier survival analysis was used to calculate overall survival. RESULTS Out of 519 patients with pan-NET, 41 patients were included. Mean follow-up time was 5.4 years. Overall survival was 9.3 years (95% Cl 6.8-11.7), and 5-year survival was 64.7% (95% CI 48.2-81.2). Patients meeting the Milan, ENETS and UNOS criteria for LT had a 5-year survival of 64.9% (95% CI 32.2-97.6), 85.7% (95% CI 59.8-100.0) and 55.4% (95% CI 26.0-84.8), respectively. CONCLUSIONS In patients with stage IV pan-NET, grade 1 and 2, with no extra abdominal disease, 5-year survival was 64.7% (95% CI 48.2-81.2). As these survival rates exceed previously published series of LT for pan-NET, the evidence base for this treatment is very weak.
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Affiliation(s)
- Josefine Kjaer
- Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Sara Smith
- Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Joakim Crona
- Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden
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17
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Muttillo EM, Mazzarella G, Picardi B, Rossi S, Cinelli L, Diana M, Baiocchini A, Felli E, Pessaux P, Felli E, Muttillo IA. Treatment strategies for neuroendocrine liver metastases: a systematic review. HPB (Oxford) 2022; 24:1832-1843. [PMID: 35794053 DOI: 10.1016/j.hpb.2022.06.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 03/19/2022] [Accepted: 06/15/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases. METHODS A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival. RESULTS 5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies. CONCLUSION Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.
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Affiliation(s)
- Edoardo M Muttillo
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy; Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France
| | - Gennaro Mazzarella
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | - Biagio Picardi
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | - Stefano Rossi
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | | | - Michele Diana
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France
| | | | - Eric Felli
- Hepatology, Department of Biomedical Research, Inselspital, University of Bern, Bern, Switzerland
| | - Patrick Pessaux
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; HPB Unit, Digestive Surgery Department, Nouvel Hopital Civil, University of Strasbourg, Strasbourg, France
| | - Emanuele Felli
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; Service Chirurgie Digestive et Transplantation Hépatique Hopital Trousseau CHU Tours, France
| | - Irnerio A Muttillo
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy.
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Liver Transplant for Non-Hepatocellular Malignancies: A Review for Radiologists. AJR Am J Roentgenol 2022; 219:590-603. [PMID: 35544376 DOI: 10.2214/ajr.22.27783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Although traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in the use of liver transplant (LT) for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens as well as the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End Stage Liver Disease (MELD) exception for tumors that meet well-defined criteria. Additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings, yet due to the relatively novel and evolving nature of LT for non-HCC malignancies, radiologists may be unaware of relevant criteria or of the implications of their imaging interpretations. Knowledge of the allocation process, background, and liver transplant selection criteria facilitates the radiologist' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.
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Siebenhüner AR, Langheinrich M, Friemel J, Schaefer N, Eshmuminov D, Lehmann K. Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors-Need for a Conductor. Cancers (Basel) 2022; 14:1478. [PMID: 35326628 PMCID: PMC8946777 DOI: 10.3390/cancers14061478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/28/2022] [Accepted: 03/10/2022] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.
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Affiliation(s)
- Alexander R. Siebenhüner
- Clinic for Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Melanie Langheinrich
- Department of Visceral Surgery, University Hospital Greifswald, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany;
| | - Juliane Friemel
- Institute for Pathologie, University Bern, Murtenstrasse 31, CH-3008 Bern, Switzerland;
| | - Niklaus Schaefer
- Department of Nuclear Medicine, University Hospital Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland;
| | - Dilmurodjon Eshmuminov
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Kuno Lehmann
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
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de Ponthaud C, Menegaux F, Gaujoux S. Updated Principles of Surgical Management of Pancreatic Neuroendocrine Tumours (pNETs): What Every Surgeon Needs to Know. Cancers (Basel) 2021; 13:5969. [PMID: 34885079 PMCID: PMC8656761 DOI: 10.3390/cancers13235969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/25/2021] [Accepted: 11/25/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (pNETs) represent 1 to 2% of all pancreatic neoplasm with an increasing incidence. They have a varied clinical, biological and radiological presentation, depending on whether they are sporadic or genetic in origin, whether they are functional or non-functional, and whether there is a single or multiple lesions. These pNETs are often diagnosed at an advanced stage with locoregional lymph nodes invasion or distant metastases. In most cases, the gold standard curative treatment is surgical resection of the pancreatic tumour, but the postoperative complications and functional consequences are not negligible. Thus, these patients should be managed in specialised high-volume centres with multidisciplinary discussion involving surgeons, oncologists, radiologists and pathologists. Innovative managements such as "watch and wait" strategies, parenchymal sparing surgery and minimally invasive approach are emerging. The correct use of all these therapeutic options requires a good selection of patients but also a constant update of knowledge. The aim of this work is to update the surgical management of pNETs and to highlight key elements in view of the recent literature.
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Affiliation(s)
- Charles de Ponthaud
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Fabrice Menegaux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Sébastien Gaujoux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
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21
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Frey S, Mirallié E, Le Bras M, Regenet N. What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review. Cancers (Basel) 2021; 13:5954. [PMID: 34885063 PMCID: PMC8656750 DOI: 10.3390/cancers13235954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
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Affiliation(s)
- Samuel Frey
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- L’institut du Thorax, Université de Nantes, CNRS, INSERM, CHU de Nantes, 44000 Nantes, France
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Eric Mirallié
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Maëlle Le Bras
- Endocrinologie, Diabétologie et Nutrition, L’institut du Thorax, CHU Nantes, 44000 Nantes, France;
| | - Nicolas Regenet
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
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22
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Nikeghbalian S, Shamsaeefar A, Eshraghian A, Kazemi K, Nikoupour H, Geramizadeh B, Azarpira N, Malek-Hosseini SA. Liver Transplantation with Simultaneous Resection of Primary Tumor Site for the Treatment of Neuroendocrine Tumors with Diffuse Liver Metastasis. J Gastrointest Cancer 2021; 52:746-749. [PMID: 32803516 DOI: 10.1007/s12029-020-00473-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Saman Nikeghbalian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, PO Box: 71994-67985, Shiraz, Iran
| | - Alireza Shamsaeefar
- Shiraz Transplant Center, Abu-Ali Sina Hospital, PO Box: 71994-67985, Shiraz, Iran
| | - Ahad Eshraghian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, PO Box: 71994-67985, Shiraz, Iran.
| | - Kourosh Kazemi
- Shiraz Transplant Center, Abu-Ali Sina Hospital, PO Box: 71994-67985, Shiraz, Iran
| | - Hamed Nikoupour
- Shiraz Transplant Center, Abu-Ali Sina Hospital, PO Box: 71994-67985, Shiraz, Iran
| | - Bita Geramizadeh
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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23
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Postrecurrence Survival After Liver Transplantation for Liver Metastases From Neuroendocrine Tumors. Transplantation 2021; 105:2579-2586. [PMID: 33908381 DOI: 10.1097/tp.0000000000003802] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Liver metastases from neuroendocrine tumors (NETs) is an accepted indication for liver transplantation (LT). Despite strict patient selection, post-LT recurrence is observed in 30-50% of cases. Postrecurrence survival is poorly investigated as well as factors influencing postrecurrence outcomes. METHODS Consecutive patients treated at a single Institution for post-LT recurrence of NET between Jan 1st, 2004 and Dec 31th, 2018 were included. Baseline patients' characteristics, data on the primary tumor, pretransplant therapies, posttransplant recurrence and treatments and long-term outcomes were prospectively collected and retrospectively analyzed. RESULTS Thirty-two patients presented with post-LT NET recurrence occurring 82.9 months (IQR 29.4-119.1) from LT, and the most common sites were abdominal lymph nodes (59.4%), peritoneum (6.3%) and lungs (6.3%). Fourteen patients (43.8%) underwent surgery with radical intent. Five- and 10-years survival after recurrence were 76.3% and 45.5%, respectively. Only time from LT to recurrence had a significant impact on post recurrence survival, being 5-years OS 89.5% versus 0% for patients recurring > 24 months after LT versus ≤ 24 months, respectively (p=.001). Moreover, for patients with Mib-1 > 2% at recurrence, 5-years OS was 87.5% versus 0% for those undergoing surgery versus loco-regional or systemic treatments (p=0.011). CONCLUSIONS The presented results, although based on a retrospective and relatively small series, show that excellent long-term survival is observed after post-LT NET recurrence, particularly in those patients recurring long after LT (> 24 months). An aggressive surgical treatment might result in a new chance of cure for a selected subgroup of patients.
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24
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Ilić D, Kunac N, Borčić T, Dinjar Kujundžić P, Mišetić Dolić Z, Sobočan N, Lalovac M, Mijić M, Međimurec G, Kocman B, Mikolašević I, Filipec Kanižaj T. Liver transplantation in patients with neuroendocrine tumors: a case series and literature review. Croat Med J 2021; 62:44-51. [PMID: 33660960 PMCID: PMC7976884 DOI: 10.3325/cmj.2021.62.44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 02/05/2021] [Indexed: 12/02/2022] Open
Abstract
Neuroendocrine tumors (NET) are a rare and heterogeneous group of neoplasms with variable biological behavior. They frequently metastasize to the liver, requiring active, multimodality treatment. Surgical resection, possible in only a minority of cases, was until recently the only potentially curative option. For unresectable NET with liver metastases, liver transplantation (LT) emerged as a potential curative treatment due to relatively slow growth and indolent behavior of the metastases. In this case series with literature review, we retrospectively analyzed the characteristics of 12 highly selected patients with metastatic NET disease as an indication for LT treated in our center. We also summarized the proposed prognostic factors, and evaluated and compared the existing selection criteria. The main poor prognostic factors in our patients were high grade NET and primary tumor in the pancreas. Inconsistent liver transplantation outcome parameters make it difficult to standardize patient selection criteria. There is a need for further studies that would fully elucidate the curative potential of LT in patients diagnosed with NET.
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Affiliation(s)
- Diana Ilić
- Diana Ilić, UH Merkur, Zajčeva 19, 10000 Zagreb, Croatia,
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25
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Muniraj T, Aslanian HR. Pancreatic Neuroendocrine Tumors. GERIATRIC GASTROENTEROLOGY 2021:1933-1951. [DOI: 10.1007/978-3-030-30192-7_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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26
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A literature-based treatment algorithm for low-grade neuroendocrine liver metastases. HPB (Oxford) 2021; 23:63-70. [PMID: 32448647 DOI: 10.1016/j.hpb.2020.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 03/03/2020] [Accepted: 04/20/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM. METHODS A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments. RESULTS Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p < 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics. CONCLUSION This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.
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27
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Manzia T, Parente A, Angelico R, Gazia C, Tisone G. The Revolution in Indication for Liver Transplantation: Will Liver Metastatic Disease Overcome the End-Stage Liver Disease in the Next Future? TRANSPLANTOLOGY 2020; 1:111-122. [DOI: 10.3390/transplantology1020011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2024] Open
Abstract
Indications for liver transplantation (LT) have constantly been evolving during the last few decades due to a better understanding of liver diseases and innovative therapies. Likewise, also the underlying causes of liver disease have changed. In the setting of transplant oncology, recent developments have pushed the boundaries of oncological indications for LT outside hepatocellular carcinoma (HCC), especially for secondary liver tumors, such as neuroendocrine and colorectal cancer. In the next years, as more evidence emerges, LT could become the standard treatment for well-selected metastatic liver tumors. In this manuscript, we review and summarize the available evidence for LT in liver tumors beyond HCC with a focus on metastatic liver malignancies, highlighting the importance of these new concepts for future implications.
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Affiliation(s)
- Tommaso Manzia
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata Hospital, Tor Vergata University of Rome, 81, Viale Oxford, 00133 Rome, Italy
| | - Alessandro Parente
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata Hospital, Tor Vergata University of Rome, 81, Viale Oxford, 00133 Rome, Italy
| | - Roberta Angelico
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata Hospital, Tor Vergata University of Rome, 81, Viale Oxford, 00133 Rome, Italy
| | - Carlo Gazia
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata Hospital, Tor Vergata University of Rome, 81, Viale Oxford, 00133 Rome, Italy
| | - Giuseppe Tisone
- Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata Hospital, Tor Vergata University of Rome, 81, Viale Oxford, 00133 Rome, Italy
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28
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Line PD, Dueland S. Liver transplantation for secondary liver tumours: The difficult balance between survival and recurrence. J Hepatol 2020; 73:1557-1562. [PMID: 32896581 DOI: 10.1016/j.jhep.2020.08.015] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/05/2020] [Accepted: 08/07/2020] [Indexed: 12/13/2022]
Abstract
Assessing the balance between survival and recurrence after transplantation for secondary liver tumours should be based on the type of cancer in question. For neuroendocrine liver metastases, high recurrence rates are clearly related to reduced long-term survival. For colorectal liver metastases, experience to date indicates that pulmonary recurrence alone has a modest impact on survival outcomes. Further studies focusing on this group of patients will be important for the development of this field of transplant oncology. Liver transplantation for secondary liver tumours should be implemented in accordance with stringent transplant criteria and preferably in the context of prospective trials. Expansion of the donor pool by utilising extended criteria donors and partial liver transplantation could be considered for this indication.
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Affiliation(s)
- Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Svein Dueland
- Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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29
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Moeckli B, Ivanics T, Claasen M, Toso C, Sapisochin G. Recent developments and ongoing trials in transplant oncology. Liver Int 2020; 40:2326-2344. [PMID: 33021344 DOI: 10.1111/liv.14621] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/17/2020] [Accepted: 07/21/2020] [Indexed: 12/17/2022]
Abstract
Over the past two decades since the introduction of the Milan criteria, the field of transplant oncology has undergone a rapid development with a rising proportion of liver transplantations being performed for oncological indications. For many patients with liver tumours, transplantation represents the only chance for cure. However, many challenges remain, such as the adequate patient selection, management of post-transplant recurrence and refinement of neoadjuvant treatment protocols. This review provides an overview of the current state of the art of liver transplantation for oncological indications such as hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastasis and metastatic neuroendocrine tumours. We also summarize the ongoing research and explore future trends. Clinical trials are currently studying new diagnostic modalities, innovative pharmacological treatments, novel surgical techniques, downstaging regimens and new indications for liver transplantation. These emerging results will continue to shape the field of transplant oncology and provide us with the necessary tools to better select, treat and follow patients with liver tumours qualifying for liver transplantation.
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Affiliation(s)
- Beat Moeckli
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Marco Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Christian Toso
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Division of General Surgery, University Health Network, Toronto, ON, Canada
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30
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Ohya Y, Hayashida S, Inomata Y. Long-Term Survival After Distal Pancreatectomy With Simultaneous Living-Donor Liver Transplant for Treatment of Pancreatic Insulinoma With Hepatic Metastasis: a Case Report. EXP CLIN TRANSPLANT 2020; 19:88-91. [PMID: 32967594 DOI: 10.6002/ect.2020.0126] [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]
Abstract
Pancreatic neuroendocrine tumors are a rare type of tumor with malignant potential, characterized by slowgrowth, frequent hepatic metastatic lesions that usually stay contained within the liver. In patients with unresectable liver metastatic pancreatic neuroendocrine tumors, liver transplant is the only treatment available. Insulinomas are the most common pancreatic neuroendocrine tumors, and 5% to 10% of insulinomas are malignant. We herein report a case of a living-donor liver transplant with distal pancreatectomy for a patient with hepatic metastatic pancreatic insulinoma with a 13-year postoperative survival.
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Affiliation(s)
- Yuki Ohya
- From the Department of Surgery, Kumamoto Rosai Hospital, Yatsushiro, Kumamoto, Japan
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31
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Kniepeiss D, Schemmer P. Transplantation bei Lebermetastasen neuroendokriner Tumoren – Heilung oder Palliation? JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2020; 13:54-58. [DOI: 10.1007/s41969-019-00087-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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32
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Liver metastases in gastroenteropancreatic neuroendocrine tumours - treatment methods. GASTROENTEROLOGY REVIEW 2020; 15:207-214. [PMID: 33005265 PMCID: PMC7509904 DOI: 10.5114/pg.2020.91501] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 11/30/2019] [Indexed: 12/13/2022]
Abstract
Surgical approaches that allow the safe treatment of multiple, bilateral, large tumours, and that combine extirpative, ablative and interventional therapies, have expanded the population of patients with neuroendocrine tumors (NET) liver metastases (LMs) who can benefit from aggressive treatment of their liver disease. Pre-treatment staging often includes the biochemical assessment of serologic markers such as serotonin, insulin, vasoactive intestinal peptide, and chromogranin, even in patients without clinically apparent hormonal excess. Radiofrequency ablation (RFA) is a technique that involves the use of thermal energy to induce coagulation necrosis, thereby destroying tumour cells. Resection plus RFA is increasingly used in patients with bilateral NET LMs. Resection is performed for large or dominant lesions, while ablation is used to treat small lesions. Hepatic arterial embolization, typically termed transarterial embolization, and transarterial chemoembolization have been shown to induce a reduction in tumour size and to ameliorate symptoms of excess hormonal secretion.
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Abstract
PURPOSE OF REVIEW Pancreatic neuroendocrine tumors (pNETs) are a rare, heterogeneous group of pancreatic neoplasms with a wide range of malignant potential. They may manifest as noninfiltrative, slow-growing tumors, locally invasive masses, or even swiftly metastasizing cancers. RECENT FINDINGS In recent years, because of the increasing amount of scientific literature available for pNETs, the classification, prognostic stratification criteria, and available consensus guidelines for diagnosis and therapy have been revised and updated. SUMMARY The vast majority of new pNET diagnoses consist of incidentally discovered lesions on cross-sectional imaging. The biologic behavior of pNETs is defined by the grade and stage of the tumor. Surgery is the only curative treatment and it, therefore, represents the first therapeutic choice for any localized pNET; however, recent evidence suggests that patients with small (<2 cm), nonfunctioning G1 tumors can be safely observed.An aggressive surgical approach towards liver metastases is recommended in selected cases, as well as liver-directed therapies for disease control. In the presence of unresectable progressive disease, somatostatin analogs, targeted therapies such as everolimus, peptide receptor radionuclide therapy, and systemic chemotherapy are all useful tools for prolonging survival.
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34
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Spolverato G, Bagante F, Tsilimigras DI, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors. MINERVA CHIR 2019; 74:399-406. [PMID: 31280548 DOI: 10.23736/s0026-4733.19.08119-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prevalence of metastatic disease in neuroendocrine tumors (NETs) is very high (60-80%) and cancer-related death among these patients is generally due to metastatic disease. Numerous treatment options for cure and disease control have been investigated for patients with neuroendocrine liver metastases (NELM). Despite the success of liver directed therapy on slowing tumor progression and palliating symptoms, the chance of being cured by liver resection is 40-50% and only roughly 20% of patients have potentially resectable disease. As such, there has been interest in liver transplantation (LT) as a potentially curative option for patients with unresectable disease. Several criteria have been proposed in order to balance long-term outcomes of patients with NELM and the problem of organ shortage including the Milan-NET criteria, the UNOS criteria and the ENETS guidelines. In the most representative studies, recurrence rate after LT has ranged from 30% to 60% with a 5-year OS ranging from 50% to 97%. This large variability is due to the retrospective nature of the studies available, which used different inclusion criteria. As such, outcomes and the prognostic factors associated with LT for NELM warrant further investigation.
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Affiliation(s)
- Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Fabio Bagante
- Department of Surgery, University of Verona, Verona, Italy
| | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA -
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35
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Barry L, McFadden DW. Gastrointestinal Carcinoid Tumors. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:939-950. [DOI: 10.1016/b978-0-323-40232-3.00080-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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36
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Vennarecci G, Mascianà G, de Werra E, Guglielmo N, Levi Sandri GB, Coluzzi M, Ettorre GM. Rectal Carcinoid Tumor With Liver Metastases Treated by Local Excision and Orthotopic Liver Transplant With Long-term Follow-up. EXP CLIN TRANSPLANT 2018; 16:506-510. [PMID: 28350289 DOI: 10.6002/ect.2016.0016] [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: 11/05/2022]
Abstract
In patients affected by unresectable liver metastases from neuroendocrine tumor, liver transplant represents currently the only realistic chance for cure. The first attempt to establish selection criteria for liver transplant in patients affected by neuroendocrine tumor liver metastases was made by Mazzaferro and associates in 2007. We report the case of a 46-year-old man who came to our institution in 2006 with right upper quadrant abdominal pain. Diagnosis of rectal neuroendocrine tumor with bilobar liver nodules was made; the patient underwent transanal local resection. A liver biopsy confirmed the metastatic nature of the hepatic lesion, showing a low-grade neuroendocrine tumor (G1, proliferation index Ki-67 <2%). The patient underwent 2 sessions of transarterial chemoembolization that resulted in stable disease. Afterward, the patient underwent a liver transplant, using the piggyback technique without a venous-venous bypass. His postoperative course was uneventful. The patient has been disease-free for 3 years. Posttransplant treatment has played a key role in increasing the overall survival of the patient and assuring him a good quality of life. He died 9 years (102 mo) after liver transplant.
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Affiliation(s)
- Giovanni Vennarecci
- Department of Surgical Oncology and Liver Transplantation, San Camillo Hospital, POIT San Camillo-INMI Lazzaro Spallanzani, Rome, Italy
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37
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Shimata K, Sugawara Y, Hibi T. Liver transplantation for unresectable pancreatic neuroendocrine tumors with liver metastases in an era of transplant oncology. Gland Surg 2018; 7:42-46. [PMID: 29629319 DOI: 10.21037/gs.2017.12.11] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Patients with pancreatic neuroendocrine tumors (pNETs) very often present with a metastatic disease at the first diagnosis. Liver transplantation (LT) for unresectable pNET with liver metastases (pNETLM) has been described to prolong survival in highly selected patients, although outcomes were worse than those of patients who underwent LT for gastrointestinal NETLM (GI-NETLM). In this review, several proposed criteria are described with their rationale and controversies. Most of the data used to establish these criteria do not reflect the recent improvements of non-surgical treatments that has changed the landscape of treatment for pNETs, including the development of peptide receptor radionuclide therapy and molecular-targeted agents (sunitinib and everolimus). Properly designed studies are necessary to define the role of down-staging and bridging therapy prior to LT incorporating systemic chemotherapy using these molecular-targeted agents. Also, given the indolent nature of low or intermediate grade pNETs, the best endpoint to compare the efficacy of each treatment option for patients with pNETLM has yet to be determined. Lastly, the definition of "unresectable" remains ambiguous. The indication of the conventional technique of two-staged liver resection with portal vein embolization or the new technique of associating liver partition and portal vein ligation for staged hepatectomy to expand the resectability of wide-spread metastatic liver tumors has been controversial. In an era of transplant oncology, LT should be the last resort for patients who are considered unresectable and otherwise untreatable after an exhaustive multidisciplinary team discussion by all experts in the field. In conclusion, although its long-term outcomes have been promising, the role of LT for unresectable pNETLM as a curative or palliative treatment remains unclear. A well-designed randomized control study is required to elucidate the clinical impact of LT for pNETLM.
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Affiliation(s)
- Keita Shimata
- Department of Transplantation and Pediatric Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Yasuhiko Sugawara
- Department of Transplantation and Pediatric Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Taizo Hibi
- Department of Transplantation and Pediatric Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
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38
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Ettorre GM, Meniconi RL, Hammel P, Deguelte S, Filippi L, Cianni R. Management of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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39
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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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40
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Chai SM, Brown IS, Kumarasinghe MP. Gastroenteropancreatic neuroendocrine neoplasms: selected pathology review and molecular updates. Histopathology 2017; 72:153-167. [DOI: 10.1111/his.13367] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Siaw M Chai
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
| | - Ian S Brown
- Envoi Pathology; Kelvin Grove; Queensland Australia
| | - M Priyanthi Kumarasinghe
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
- School of Pathology and Laboratory Medicine; University of Western Australia; Perth Australia
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41
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Sposito C, Droz Dit Busset M, Citterio D, Bongini M, Mazzaferro V. The place of liver transplantation in the treatment of hepatic metastases from neuroendocrine tumors: Pros and cons. Rev Endocr Metab Disord 2017; 18:473-483. [PMID: 29359266 DOI: 10.1007/s11154-017-9439-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome differences for available treatments, due to the long course of disease, surgery for MNETs remains the most effective option in terms of survival and symptom control. Since MNETs frequently present as an oligo-metastatic, liver-limited disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as a potential curative treatment. Nevertheless, experience with LT for MNETs is limited and burdened by highly heterogeneous outcomes and significant recurrence rate, mostly explained by the variability of selection criteria. Several prognostic factors have been identified: extended surgery on primary tumor associated to LT, elderly patients, pancreatic primary (pNET), extensive liver involvement, poorly differentiated tumors, high Ki67 levels and short wait time to LT. A proper patients' selection based on these data (Milan NET criteria) allows a significant survival advantage over non-transplant strategies, with excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best option for selected patients with MNETs. The use of organs for MNETs is therefore justified.
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Affiliation(s)
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Michele Droz Dit Busset
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Davide Citterio
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy.
- University of Milan, Milan, Italy.
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42
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Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, Beal EW, Felekouras E, Vernadakis S, Fung JJ, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review. Surgery 2017; 162:525-536. [PMID: 28624178 DOI: 10.1016/j.surg.2017.05.006] [Citation(s) in RCA: 104] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Revised: 04/28/2017] [Accepted: 05/02/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver transplantation to treat neuroendocrine tumors, especially in the setting of diffuse liver involvement not amenable to operative resection remains controversial. We sought to perform a systematic review of the current literature to summarize data on patients undergoing liver transplantation with neuroendocrine tumors liver metastases as the indication. METHODS A systematic review was conducted in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were identified using 3 distinct databases through March 2017: Medline (PubMed), ClinicalTrials.gov, and Cochrane library, Cochrane Central Register of Controlled Trials using a search algorithm: "(neuroendocrine or NET) and transplantation and liver." RESULTS From the 1,216 records retrieved, 64 studies were eligible. Overall, 4 studies presented data from registries, namely the European Liver Transplant Registry and the United Network for Organ Transplantation/Organ Procurement and Transplantation Network databases, 3 were multicenter studies. The largest cohort of data on patients undergoing liver transplantation for neuroendocrine tumors liver metastasis indication were from single center studies comprising a total of 279 patients. Pancreas was the primary tumor site for most patients followed by the ileum. Several studies reported that more than half of patients presented with synchronous disease (55.9% and 57.7%); in contrast, metachronous neuroendocrine tumors liver metastasis ranged from 17.7% to 38.7%. Overall, recurrence after liver transplantation ranged from 31.3% to 56.8%. Reported 1-, 3-, and 5-year overall survival was 89%, 69%, and 63%, respectively. Several prognostic factors associated with worse long-term survival including transplantation >50% liver tumor involvement, high Ki67, as well as a pancreatic neuroendocrine tumors versus gastrointestinal neuroendocrine tumors tumor location. CONCLUSION Liver transplantation may provide a survival benefit among patients with diffuse neuroendocrine tumors metastases to the liver. However, due to high recurrence rates, strict selection of patients is critical. Due to the scarcity of available grafts and the lack of level 1 evidence, the recommendations to endorse liver transplantation for extensive liver neuroendocrine tumors metastases warrants ongoing deliberations.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Diamantis I Tsilimigras
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Ntanasis-Stathopoulos
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Eliza W Beal
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Evangelos Felekouras
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Spiridon Vernadakis
- Transplantation Unit, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - John J Fung
- Department of Surgery, University of Chicago Medicine Transplant Institute, University of Chicago, Chicago, IL
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH.
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Berumen J, McCarty P, Mo J, Newton K, Fairbanks T, Mekeel K, Hemming A. Combined liver transplant and pancreaticoduodenectomy for inflammatory hilar myofibroblastic tumor: Case report and review of the literature. Pediatr Transplant 2017; 21. [PMID: 28000317 DOI: 10.1111/petr.12846] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/22/2016] [Indexed: 12/14/2022]
Abstract
IMT, previously known as IPT, is a relatively rare tumor that was originally described in the lungs, but case reports have reported the tumor in almost every organ system. Surgical resection is typically the mainstay of therapy; however, tumors have also been shown to respond to chemotherapy or anti-inflammatory therapy and some have spontaneously regressed. We present a literature review and case report representing the first documentation to date of liver transplant combined with PD for surgical resection of a myofibroblastic tumor non-responsive to medical therapy.
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Affiliation(s)
| | - Patrick McCarty
- University of California San Diego - Surgery, La Jolla, CA, USA
| | - Jun Mo
- University of California San Diego - Surgery, La Jolla, CA, USA
| | - Kimberly Newton
- University of California San Diego - Surgery, La Jolla, CA, USA
| | | | - Kristin Mekeel
- University of California San Diego - Surgery, La Jolla, CA, USA
| | - Alan Hemming
- University of California San Diego - Surgery, La Jolla, CA, USA
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44
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Maxwell JE, Howe JR. Pancreatic neuroendocrine tumors. BLUMGART'S SURGERY OF THE LIVER, BILIARY TRACT AND PANCREAS, 2-VOLUME SET 2017:997-1006.e3. [DOI: 10.1016/b978-0-323-34062-5.00065-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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45
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Mazzaferro V, Sposito C, Coppa J, Miceli R, Bhoori S, Bongini M, Camerini T, Milione M, Regalia E, Spreafico C, Gangeri L, Buzzoni R, de Braud FG, De Feo T, Mariani L. The Long-Term Benefit of Liver Transplantation for Hepatic Metastases From Neuroendocrine Tumors. Am J Transplant 2016; 16:2892-2902. [PMID: 27134017 DOI: 10.1111/ajt.13831] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 04/10/2016] [Accepted: 04/10/2016] [Indexed: 01/25/2023]
Abstract
Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty-eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan-NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long-term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow-up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time-to-progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4-23.0; p = 0.001). Adjusted transplant-related survival benefit was 6.82 months (95% CI: 1.10-12.54; p = 0.019) and 38.43 months (95% CI: 21.41-55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long-term outcome. Transplant-related survival benefit increases over time and maximizes after 10 years.
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Affiliation(s)
- V Mazzaferro
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - C Sposito
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - J Coppa
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - R Miceli
- Trial Office and Biomedical Statistics, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
| | - S Bhoori
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - M Bongini
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - T Camerini
- Trial Office and Biomedical Statistics, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
| | - M Milione
- Pathology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
| | - E Regalia
- Surgery and Hepatology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - C Spreafico
- Interventional Radiology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
| | - L Gangeri
- Psychology, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
| | - R Buzzoni
- Medical Oncology Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - F G de Braud
- Medical Oncology Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), University of Milan, Milan, Italy
| | - T De Feo
- North Italian Transplant Procurement Agency, Organ and Tissue Transplant Immunology, IRCCS Policlinico Hospital, Milan, Italy
| | - L Mariani
- Trial Office and Biomedical Statistics, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy
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46
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Chiruvella A, Kooby DA. Surgical Management of Pancreatic Neuroendocrine Tumors. Surg Oncol Clin N Am 2016; 25:401-21. [PMID: 27013372 DOI: 10.1016/j.soc.2015.12.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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47
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Kulik U, Lehner F, Bektas H, Klempnauer J. Liver Resection for Non-Colorectal Liver Metastases - Standards and Extended Indications. VISZERALMEDIZIN 2016; 31:394-8. [PMID: 26889142 PMCID: PMC4748777 DOI: 10.1159/000439419] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Background Due to the uncertain benefit of liver resection for non-colorectal liver metastases (NCLM), patient selection for surgery is generally difficult. Therefore, the aim of this article was to propose standard and extended indications for liver resection in this heterogeneous disease collective. Methods Review of the literature. Results The myriad of biologically different primary tumor entities as well as the mostly small and retrospective studies investigating the benefit of surgery for NCLM limits the proposal of general recommendations. Only resection of neuroendocrine liver metastases (NELM) appears to offer a clear benefit with a 5- and 10-year overall survival (OS) of 74 and 51%, respectively, in the largest series. Resection of liver metastases from genitourinary primaries might offer reasonable benefit in selected cases – with a 5-year OS of up to 61% for breast cancer and of 38% for renal cell cancer. The long-term outcome following surgery for other entities was remarkably poorer, e.g., gastric cancer, pancreatic cancer, and melanoma reached a 5-year OS of 20-42, 17-25, and about 20%, respectively. Conclusion Liver resection for NELM can be defined as a standard indication for the resection of NCLM while lesions of genitourinary origin might be defined as an extended indication.
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Affiliation(s)
- Ulf Kulik
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hanover, Germany
| | - Frank Lehner
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hanover, Germany
| | - Hüseyin Bektas
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hanover, Germany
| | - Jürgen Klempnauer
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hanover, Germany
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48
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Berardi R, Rinaldi S, Torniai M, Morgese F, Partelli S, Caramanti M, Onofri A, Polenta V, Pagliaretta S, Falconi M, Cascinu S. Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy--A literature review. Crit Rev Oncol Hematol 2016; 98:264-274. [PMID: 26643525 DOI: 10.1016/j.critrevonc.2015.11.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 03/29/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different malignant potential and behavior. Many treatment options are available. Surgery should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs, useful for symptoms control in functioning tumors, are also effective to inhibit tumor progression in specific settings. The multi-TKI sunitinib and of the mTOR-inhibitor everolimus are efficacy for metastatic pancreatic NET (P-NET) treatment. Chemotherapy is generally used in symptomatic and progressive NETs. Peptide receptor radionuclide therapy (PRRT) should be recommended after failure of medical therapy. For tumors confined to the liver ablative techniques should be considered. Nevertheless a shared therapeutic sequence for GEP-NET treatment still does not exist. In this review, we analyzed available data trying to identify the better treatment strategy and to suggest potential therapeutic algorithms distinguishing P-NETs from gastrointestinal NETs (GI-NETs).
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Affiliation(s)
- Rossana Berardi
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy.
| | - Silvia Rinaldi
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Mariangela Torniai
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Francesca Morgese
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Stefano Partelli
- Chirurgia del Pancreas, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Miriam Caramanti
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Azzurra Onofri
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Vanessa Polenta
- Chirurgia del Pancreas, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Silvia Pagliaretta
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Massimo Falconi
- Chirurgia del Pancreas, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
| | - Stefano Cascinu
- Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy
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49
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Abstract
Neuroendocrine neoplasms represent a heterogeneous group of cancers arising from a variety of neuroendocrine cell types. In general, these tumors (NET) are asymptomatic and are discovered late once metastatic disease is present (40-80%). The liver is the most common organ involved when metastases occur (40-93%), followed by bone (12-20%) and lungs (8-10%). A number of different therapeutic options are available for patients with hepatic metastases including surgical resection, transplantation, transarterial chemoembolization, radiofrequency and microwave ablation, radioembolization (Y90), chemotherapy, somatostatin analogues and molecular targeted therapies. Surgical resection is still considered the treatment of choice and provides excellent disease control with an overall survival of 47-92%. Liver transplantation has been advocated in selected patients with bilateral unresectable symptomatic liver metastases. The aim of this study is to review the existing literature emphasizing on the role of transplantation to treat patients with liver metastases from NET.
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Affiliation(s)
- Valery Vilchez
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Roberto Gedaly
- Department of Surgery-Transplant Division, University of Kentucky, Lexington, KY, USA.
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50
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Abstract
Liver is the commonest site for metastasis in patients with neuroendocrine tumors (NETs); it occurs in 45-95% of patients. Available treatment options include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy. Typically, a multidisciplinary approach is a cornerstone for decision making while dealing with this aggressive disease. This review will focus on the performance and safety of open, laparoscopic, and liver transplant surgical approaches in NETs patients with liver metastases.
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Affiliation(s)
- Emad Kandil
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Ahmad Saeed
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Joseph Buell
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA
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