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Allkushi E, Wehrle CJ, Kim J, Khalil M, Kwon DCH, Fujiki M, Pinna AD, Miller C, Schlegel A, Aucejo F, Hashimoto K, Pita A. Expanding Indications in Transplant Oncology. Cancers (Basel) 2025; 17:773. [PMID: 40075625 PMCID: PMC11898796 DOI: 10.3390/cancers17050773] [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: 01/20/2025] [Revised: 02/16/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
Liver transplantation is aptly described as the only curative treatment for cirrhosis and cirrhosis with co-morbid hepatocellular carcinoma (HCC). Its utility in the management of various other primary and secondary liver cancers is gaining traction rapidly, with more thorough assessments on broader populations continuing to emerge. Most prominently, this includes colorectal cancer liver metastasis (CRLM), cholangiocarcinoma (CCA), neuroendocrine tumors (NETs), and more. Furthermore, despite being a well described treatment for HCC for many years, growing evidence supports a change in oncological strategy for HCC, with broadened selection criteria and more advanced systemic and locoregional therapies available. Our review aims to describe the evidence supporting the expansion of indications and selection criteria for liver transplantation in various oncologic indications of primary and secondary liver tumors.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Alejandro Pita
- Transplantation Center, Department of Liver Transplantation, Cleveland Clinic, Cleveland, OH 44195, USA (C.J.W.); (J.K.); (M.K.); (D.C.H.K.); (M.F.); (A.D.P.); (A.S.); (K.H.)
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2
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Pandrowala SA, Kapoor D, Kunte A, Chopde A, Puranik A, Dev ID, Parghane R, Basu S, Ramaswamy A, Ostwal V, Chaudhari VA, Bhandare MS, Shrikhande SV. Factors Predicting Prognosis in Metastatic Grade 1 Gastro-entero-pancreatic Neuroendocrine Tumors. J Gastrointest Cancer 2024; 55:1220-1228. [PMID: 38874852 PMCID: PMC11347461 DOI: 10.1007/s12029-024-01077-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2024] [Indexed: 06/15/2024]
Abstract
INTRODUCTION The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) has steadily increased. These tumors are considered relatively indolent even when metastatic. What determines survival outcomes in such situations is understudied. MATERIALS AND METHODS Retrospective analysis of a prospectively maintained NET clinic database, to include patients of metastatic grade 1 GEP-NET, from January 2018 to December 2021, to assess factors affecting progression-free survival (PFS). RESULTS Of the 589 patients of GEP-NET treated during the study period, 100 were grade 1, with radiological evidence of distant metastasis. The median age was 50 years, with 67% being men. Of these, 15 patients were observed, while 85 patients received treatment in the form of surgery (n = 32), peptide receptor radionuclide therapy (n = 50), octreotide LAR (n = 22), and/or chemotherapy (n = 4), either as a single modality or multi-modality treatment. The median (PFS) was 54.5 months. The estimated 3-year PFS and 3-year overall survival rates were 72.3% (SE 0.048) and 93.4% (SE 0.026), respectively. On Cox regression, a high liver tumor burden was the only independent predictor of PFS (OR 3.443, p = 0.014). The 5-year OS of patients with concomitant extra-hepatic disease was significantly lower than that of patients with liver-limited disease (70.7% vs. 100%, p = 0.017). CONCLUSION A higher burden of liver disease is associated with shorter PFS in patients with metastatic grade I GEP-NETs. The OS is significantly lower in patients with associated extrahepatic involvement. These parameters may justify a more aggressive treatment approach in metastatic grade 1 GEP-NETs.
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Affiliation(s)
- Saneya A Pandrowala
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
| | - Deeksha Kapoor
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
| | - Aditya Kunte
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
| | - Amit Chopde
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
| | - Ameya Puranik
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, 400012, India
| | - Indraja Devidas Dev
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, 400012, India
| | - Rahul Parghane
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Mumbai, Maharashtra, 400012, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Mumbai, Maharashtra, 400012, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, 400012, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, 400012, India
| | - Vikram A Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
| | - Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India.
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
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Strosberg JR, Al-Toubah T. Surgical management of metastatic neuroendocrine tumors: beyond the realm of evidence-based medicine. Hepatobiliary Surg Nutr 2024; 13:551-553. [PMID: 38911215 PMCID: PMC11190503 DOI: 10.21037/hbsn-24-90] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/15/2024] [Indexed: 06/25/2024]
Affiliation(s)
- Jonathan R Strosberg
- Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, FL, USA
| | - Taymeyah Al-Toubah
- Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, FL, USA
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Okumura K, Dhand A, Hanna K, Misawa R, Sogawa H, Veillette G, Nishida S. Indications and outcomes of liver transplantation for liver tumors in the United States. SURGERY IN PRACTICE AND SCIENCE 2024; 17:100245. [PMID: 39845637 PMCID: PMC11749412 DOI: 10.1016/j.sipas.2024.100245] [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: 08/31/2023] [Revised: 04/01/2024] [Accepted: 04/01/2024] [Indexed: 01/24/2025] Open
Abstract
Background While hepatocellular carcinoma (HCC) remains the leading cause of liver transplant (LT) for liver tumors, indications have broadened over the years. Data regarding patient characteristics and outcomes of LT for liver tumors are limited. Methods From Jan-2002 to March-2022, 14,406 LT recipients for various liver tumors were identified in United Network for Organ Sharing database. Overall post-transplant survival analysis was performed with Kaplan-Meier method and multivariable Cox proportional-hazards model. Results During the study period, indications for LT for various hepatic tumors were HCC (88.5 %), benign tumors (5.1 %), cholangiocarcinoma (3.9 %), angiosarcoma (0.7 %), bile duct cancer (0.7 %), secondary tumors (0.5 %) and others (0.7 %). Compared to non-HCC, LT recipients for HCC were older (median age 61 vs 54 years, P < 0.001), more often male (77% vs 48 %, P < 0.001), more often Hispanic (16% vs 8.0 %), had higher BMI (28.2 vs 25.3, P < 0.001) and higher prevalence of Hepatitis C (53% vs 3.9 %, P < 0.001). Donor characteristics across various groups were similar. One-year survival in LT recipients of HCC was higher (HCC: 91.7% vs. non-HCC: 90.3 %) with adjusted Hazard Ratio (aHR) of 0.87; 95 % CI 0.77-0.99, P = 0.033 in a multivariable Cox regression analysis. Compared to HCC, survival outcomes were worse in cholangiocarcinoma (aHR 1.70; 95 %CI 1.43-2.01, P < 0.001), bile duct cancer (aHR 3.03; 95 %CI 2.12-4.33, P < 0.001), secondary tumors including colon cancer and neuroendocrine tumors (aHR 1.88; 95 % CI 1.24-2.85, P = 0.003), with best survival in patients with benign tumors (aHR 0.57; 95 %CI 0.46-0.70, P < 0.001). Conclusions LT is performed for various liver tumors with variable outcomes among these primary indications.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Kamil Hanna
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
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Kartik A, Armstrong VL, Stucky CC, Wasif N, Fong ZV. Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:1501. [PMID: 38672582 PMCID: PMC11048062 DOI: 10.3390/cancers16081501] [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: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.
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Affiliation(s)
| | | | | | | | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ 85054, USA
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Van Den Heede K, van Beek DJ, Van Slycke S, Borel Rinkes I, Norlén O, Stålberg P, Nordenström E. Surgery for advanced neuroendocrine tumours of the small bowel: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES). Br J Surg 2024; 111:znae082. [PMID: 38626261 DOI: 10.1093/bjs/znae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 02/19/2024] [Accepted: 03/04/2024] [Indexed: 04/18/2024]
Abstract
BACKGROUND Small bowel neuroendocrine tumours often present with locally advanced or metastatic disease. The aim of this paper is to provide evidence-based recommendations regarding (controversial) topics in the surgical management of advanced small bowel neuroendocrine tumours. METHODS A working group of experts was formed by the European Society of Endocrine Surgeons. The group addressed 11 clinically relevant questions regarding surgery for advanced disease, including the benefit of primary tumour resection, the role of cytoreduction, the extent of lymph node clearance, and the management of an unknown primary tumour. A systematic literature search was performed in MEDLINE to identify papers addressing the research questions. Final recommendations were presented and voted upon by European Society of Endocrine Surgeons members at the European Society of Endocrine Surgeons Conference in Mainz in 2023. RESULTS The literature review yielded 1223 papers, of which 84 were included. There were no randomized controlled trials to address any of the research questions and therefore conclusions were based on the available case series, cohort studies, and systematic reviews/meta-analyses of the available non-randomized studies. The proposed recommendations were scored by 38-51 members and rated 'strongly agree' or 'agree' by 64-96% of participants. CONCLUSION This paper provides recommendations based on the best available evidence and expert opinion on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours.
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Affiliation(s)
- Klaas Van Den Heede
- Department of General and Endocrine Surgery, Onze-Lieve-Vrouw (OLV) Hospital Aalst-Asse-Ninove, Aalst, Belgium
| | - Dirk-Jan van Beek
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Sam Van Slycke
- Department of General and Endocrine Surgery, Onze-Lieve-Vrouw (OLV) Hospital Aalst-Asse-Ninove, Aalst, Belgium
- Department of General Surgery, AZ Damiaan, Ostend, Belgium
- Department of Head and Skin, University Hospital Ghent, Ghent, Belgium
| | - Inne Borel Rinkes
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Erik Nordenström
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
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Rai A, Sproule L, Larman T, Oshima K, Rhee D, Ng K, King E, Mogul D, Lemberg K. Liver transplant for primary biliary tract neuroendocrine tumor in a nine-year-old girl. Pediatr Transplant 2024; 28:e14732. [PMID: 38433619 DOI: 10.1111/petr.14732] [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: 05/18/2023] [Revised: 11/28/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Neuroendocrine tumors (NETs) are rare epithelial neoplasms that arise most commonly from the gastrointestinal tract. In pediatrics, the most common site of origin is in the appendix, with the liver being the most common site of metastasis. Neuroendocrine tumors arising from the biliary tract are extremely rare. METHODS We describe a case of a nine-year-old girl who presented with obstructive cholestasis and was found to have multiple liver masses identified on biopsy as well-differentiated neuroendocrine tumor with an unknown primary tumor site. RESULT The patient underwent extensive investigation to identify a primary tumor site, including endoscopy, endoscopic ultrasound, and capsule endoscopy. The patient ultimately underwent definitive management with liver transplant, and on explant was discovered to have multiple well-differentiated neuroendocrine tumors, WHO Grade 1, with extensive infiltration into the submucosa of bile duct, consistent with primary biliary tract neuroendocrine tumor. CONCLUSION Identifying the site of the primary tumor in NETs found within the liver can be challenging. To determine if an extrahepatic primary tumor exists, workup should include endoscopy, EUS, and capsule endoscopy. Children with well-differentiated hepatic NETs, with no identifiable primary tumor, and an unresectable tumor, are considered favorable candidates for liver transplantation.
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Affiliation(s)
- Anjali Rai
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Lauren Sproule
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Biochemistry, McGill University, Montreal, Canada
| | - Tatianna Larman
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kiyoko Oshima
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Daniel Rhee
- Division of General Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kenneth Ng
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth King
- Division of Transplant Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Douglas Mogul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kathryn Lemberg
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Loosen SH, Leyh C, Neumann UP, Bock H, Weigel C, Luedde T, Roderburg C. Liver transplantation meets gastrointestinal cancer. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:62-72. [PMID: 38195110 DOI: 10.1055/a-2226-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
Liver transplantation (LT) has emerged as a standard of care for patients with end-stage liver disease, providing a life-saving intervention for patients with severely compromised liver function in both the acute and chronic setting. While LT has also become a routine procedure for early-stage hepatocellular carcinoma (HCC), offering a potential cure by treating both the tumor and the underlying liver disease, its relevance in the context of other malignancies such as cholangiocellular carcinoma (CCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) or liver metastases is still the subject of intense debate and no definite recommendations have yet been established. This review summarizes the current therapeutic standards in the context of LT for gastrointestinal malignancies and provides a reflection and outlook on current scientific and clinical developments.
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Affiliation(s)
- Sven H Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Catherine Leyh
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Ulf Peter Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery and Transplantation, University Hospital Essen, Essen, Germany
| | - Hans Bock
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christian Weigel
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
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Kuncewicz M, Jaszczyszyn IP, Karaban K, Rykowski P, Krasnodębski M, Morawski M, Kruk E, Koperski Ł, Zieniewicz K, Krawczyk M, Grąt M. Predictors of Long-Term Outcomes After Liver Transplantation for Unresectable Metastatic Neuroendocrine Tumors. Ann Transplant 2023; 28:e941212. [PMID: 37986542 PMCID: PMC10675983 DOI: 10.12659/aot.941212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/28/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Malignant and benign neuroendocrine tumors (NET) share many histopathological features. Liver transplantation (LT) is one of the liver-directed therapies for neuroendocrine liver metastases (NELM). The aim of this study was to determine the outcomes of patients undergoing LT for NELM. MATERIAL AND METHODS This was a retrospective study that included 19 patients who underwent LT for unresectable NELM between December 1989 and December 2022 in the Department of General, Transplant, and Liver Surgery of the Medical University of Warsaw. Kaplan-Meier estimator and Cox proportional hazards regression were used for statistical analyses. RESULTS The primary tumor was located most frequently in the pancreas. The median follow-up was 72.5 months. The overall survival (OS) was 94.7%, 88.0%, 88.0%, 70.4%, and 49.3% after 1, 3, 5, 10, and 15 years, respectively. Accordingly, the recurrence-free survival (RFS) rates were 93.8%, 72.9%, 64.8%, 27.8%, and 27.8% after 1, 3, 5, 10, and 15 years, respectively. Ki-67 index ≥5% was found as a risk factor for both worse OS (hazard ratio (HR) 7.13, 95% confidence intervals (95% CI) 1.32-38.63, P=0.023) and RFS (HR 13.68, 95% CI 1.54-121.52, P=0.019). Recipient age ≥55 years was a risk factor for worse RFS (P=0.046, HR 5.47, 95% CI 1.03-29.08). Multivariable analysis revealed Ki-67 ≥5% as the sole independent factor for worse OS (HR 13.78, 95% CI 1.48-128.56, P=0.021). CONCLUSIONS Patients with unresectable NELM achieve great OS and satisfying RFS after LT. The risk factors associated with worse outcomes are attributed to primary tumor aggressiveness.
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Affiliation(s)
- Mikołaj Kuncewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Igor Piotr Jaszczyszyn
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Kacper Karaban
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Paweł Rykowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Emilia Kruk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Łukasz Koperski
- Department of Pathology, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Marek Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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10
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Harrelson A, Wang R, Stewart A, Ingram C, Gillis A, Rose JB, El-Rayes B, Azmi A, Chen H. Management of neuroendocrine tumor liver metastases. Am J Surg 2023; 226:623-630. [PMID: 37657968 DOI: 10.1016/j.amjsurg.2023.08.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 07/15/2023] [Accepted: 08/14/2023] [Indexed: 09/03/2023]
Abstract
BACKGROUND Neuroendocrine Tumors (NETs) are a group of tumors that arise from neuroendocrine cells, and are increasing in incidence worldwide. These tumors often metastasize to the liver, and management of these neuroendocrine tumor liver metastases (NELMs) requires a multi-disciplinary approach. We aim to provide a comprehensive update for treatment of NELMs. METHODS We completed a comprehensive systemic review of papers involving the diagnosis, treatment, and outcomes of NELMs. We identified 1612 records via Scopus database literature search. Two independent authors reviewed these records, with 318 meeting criteria for inclusion in the final systemic review. RESULTS Primary tumor resection with resection of liver metastases is the treatment of choice for patients with NELMs. Liver-directed therapies and liver transplantation can be considered for patients with unresectable liver metastases. Systemic medical therapy is used for managing tumor burden and symptoms caused by NELMs. CONCLUSIONS Advancement in liver-directed and targeted systemic therapies provide improved options for patients with unresectable tumors. Given the complexity of NELMs, management of NELMs necessitates multidisciplinary teams at comprehensive health centers.
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Affiliation(s)
- Alex Harrelson
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rongzhi Wang
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Addison Stewart
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Clark Ingram
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Andrea Gillis
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - J Bart Rose
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Bassel El-Rayes
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Asfar Azmi
- Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA
| | - Herbert Chen
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
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Sampaio RL, Coelho GR, Quidute ARP, Rocha Filho DRD, Soares CEL, Garcia JHP. LIVER TRANSPLANT FOR METASTATIC NEUROENDOCRINE TUMORS: A SINGLE-CENTER REPORT. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1750. [PMID: 37466569 DOI: 10.1590/0102-672020230032e1750] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 05/25/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.
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Affiliation(s)
- Raquel Lima Sampaio
- Hospital Universitário Walter Cantídio, Digestive Surgical Unit - Fortaleza (CE), Brazil
| | - Gustavo Rego Coelho
- Hospital Universitário Walter Cantídio, Digestive Surgical Unit - Fortaleza (CE), Brazil
- Hospital Universitário Walter Cantídio, Liver Transplant Unit - Fortaleza (CE), Brazil
- Hospital São Carlos, Liver Transplant Unit - Fortaleza (CE), Brazil
| | | | | | | | - José Huygens Parente Garcia
- Hospital Universitário Walter Cantídio, Digestive Surgical Unit - Fortaleza (CE), Brazil
- Hospital Universitário Walter Cantídio, Liver Transplant Unit - Fortaleza (CE), Brazil
- Hospital São Carlos, Liver Transplant Unit - Fortaleza (CE), Brazil
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12
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Williams JK, Schwarz JL, Keutgen XM. Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review. Hepatobiliary Surg Nutr 2023; 12:69-83. [PMID: 36860243 PMCID: PMC9944533 DOI: 10.21037/hbsn-22-238] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 10/10/2022] [Indexed: 01/18/2023]
Abstract
Background and Objective Pancreatic neuroendocrine tumors (PanNETs) are derived from the islet cells of the pancreas and have been increasing in incidence. Most of these tumors are nonfunctional although some can secrete hormones and lead to hormone-specific clinical syndromes. Surgery is the mainstay of treatment for localized tumors, however, surgical resection is controversial in metastatic PanNETs. This narrative review seeks to summarize the current literature surrounding surgery, specifically in the controversial area of metastatic PanNETs, review current treatment paradigms, and understand the benefits of surgery in this group of patients. Methods Authors searched PubMed using the terms "surgery pancreatic neuroendocrine tumor", "metastatic neuroendocrine tumor", and "liver debulking neuroendocrine tumor" from January 1990 to June 2022. Only English language publications were considered. Key Content and Findings There is no consensus among the leading specialty organizations regarding surgery for metastatic PanNETs. When considering surgery for metastatic PanNETs, tumor grade and morphology, location of the primary tumor, extra-hepatic or extra-abdominal disease, as well as liver tumor burden and metastatic distribution should be considered. Because the liver is the most common site of metastasis and liver failure is the most common cause of death in patients with hepatic metastases, attention is centered here on debulking and other ablative techniques. Liver transplantation is rarely used for hepatic metastases but could be beneficial in a small subset of patients. Retrospective studies have demonstrated improvement in survival and symptoms after surgery for metastatic disease, but the lack of prospective randomized control trials significantly limits analysis of surgical benefits in patients with metastatic PanNETs. Conclusions Surgery is the standard of care for localized PanNETs, while it remains controversial in metastatic disease. Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients. However, most of the studies on which recommendations are based in this population are retrospective in nature and are subject to selection bias. This presents an opportunity for future investigation.
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Affiliation(s)
- Jelani K Williams
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
| | - Jason L Schwarz
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
| | - Xavier M Keutgen
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
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13
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Que QY, Zhang LC, Bao JQ, Ling SB, Xu X. Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:397-408. [PMID: 35734618 PMCID: PMC9160682 DOI: 10.4240/wjgs.v14.i5.397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/19/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.
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Affiliation(s)
- Qing-Yang Que
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Lin-Cheng Zhang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Jia-Qi Bao
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Sun-Bin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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14
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Clinicopathological Characteristics of Nonfunctional Pancreatic Neuroendocrine Neoplasms and the Effect of Surgical Treatment on the Prognosis of Patients with Liver Metastases: A Study Based on the SEER Database. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3689895. [PMID: 35720036 PMCID: PMC9200579 DOI: 10.1155/2022/3689895] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/23/2022] [Accepted: 04/11/2022] [Indexed: 12/13/2022]
Abstract
Background The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases. Methods pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors. Results From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade. Conclusions The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades.
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15
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Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome. Surgery 2022; 172:559-566. [PMID: 35437162 PMCID: PMC9681028 DOI: 10.1016/j.surg.2022.03.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 02/11/2022] [Accepted: 03/14/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Neuroendocrine tumors can cause ectopic Cushing syndrome, and most patients have metastatic disease at diagnosis. We identified risk factors for outcome, evaluated ectopic Cushing syndrome management, and explored the role of bilateral adrenalectomy in this population. METHODS This was a retrospective study including patients with diagnosis of ectopic Cushing Syndrome secondary to neuroendocrine tumors with adrenocorticotropic hormone secretion treated at our quaternary referral center over a 40-year period (1980-2020). RESULTS Seventy-six patients were included. Mean age at diagnosis was 46.3 ± 15.8 years. Most patients (N = 61, 80%) had metastases at ectopic Cushing syndrome diagnosis. Average follow-up was 2.9 ± 3.7 years (range, 4 months-17.2 years). Patients with neuroendocrine tumors before ectopic Cushing syndrome had more frequent metastatic disease and resistant ectopic Cushing syndrome. Patients with de novo hyperglycemia, poor neuroendocrine tumor differentiation, and metastatic disease had worse survival. Of those with nonmetastatic disease, 8 (53%) had ectopic Cushing syndrome resolution after neuroendocrine tumor resection, 3 (20%) were medically controlled, and 4 (27%) underwent bilateral adrenalectomy. In patients with metastatic neuroendocrine tumors, hypercortisolism was initially medically managed in 92%, 3% underwent immediate bilateral adrenalectomy, 2% had control after primary neuroendocrine tumor debulking, and 2% were lost to follow-up. Medical treatment resulted in hormonal control in 7 (13%) patients. Of the 49 patients with metastatic disease and medically resistant ectopic Cushing syndrome, 23 ultimately had bilateral adrenalectomy with ectopic Cushing syndrome cure in all. CONCLUSION Patients with neuroendocrine tumors before ectopic Cushing syndrome development were more likely metastatic and had worse survival. De novo hyperglycemia and poor neuroendocrine tumor differentiation were predictive of worse prognosis. Medical control of hypercortisolism is difficult to achieve in patients with neuroendocrine tumors-ectopic Cushing syndrome. Well-selected patients may benefit from bilateral adrenalectomy early in the treatment algorithm, and multidisciplinary management is essential in this complex disease.
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16
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Nagel I, Herrmann K, Lahner H, Rischpler C, Weber F. Combined medical therapy, nuclear medicine therapy and other therapies in metastatic neuroendocrine tumor. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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17
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Acher AW, Rahnemai-Azar AA, Weber SM, Pawlik TM. Surgical Approach to Pancreas, Liver, Biliary Physiologic Impairment. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:31-49. [DOI: 10.1007/978-981-19-0063-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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Kubal C, Mihaylov P, Holden J. Oncologic indications of liver transplantation and deceased donor liver allocation in the United States. Curr Opin Organ Transplant 2021; 26:168-175. [PMID: 33650998 DOI: 10.1097/mot.0000000000000866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.
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Affiliation(s)
| | | | - John Holden
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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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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21
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Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors. J Clin Med 2020; 9:jcm9072319. [PMID: 32708330 PMCID: PMC7408509 DOI: 10.3390/jcm9072319] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/14/2020] [Accepted: 07/16/2020] [Indexed: 12/19/2022] Open
Abstract
Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.
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