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Semaan S, Connor AA, Saharia A, Kodali S, Elaileh A, Patel K, Soliman N, Basra T, Victor DW, Simon CJ, Cheah YL, Hobeika MJ, Mobley CM, Dhingra S, Schwartz MR, Maqsood A, Heyne K, Abdelrahim M, Li XC, Javle M, Vauthey JN, Gaber AO, Ghobrial RM. Transplantation for Peri-Hilar and Intrahepatic Cholangiocarcinoma With mTOR Immunosuppression. Transplant Proc 2025:S0041-1345(25)00057-0. [PMID: 39939239 DOI: 10.1016/j.transproceed.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/24/2025] [Accepted: 02/06/2025] [Indexed: 02/14/2025]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Outcomes from combination systemic, loco-regional therapy (LRT) and liver transplantation (LT) are improving, but more granular data are needed to inform evidence-based management, including patient selection and immunosuppression. METHODS Patients with peri-hilar (PH) and intrahepatic (IH) CCA who underwent LT at a single center between January 2008 and February 2023 were reviewed retrospectively. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) with significance determined by Cox proportional hazards model. RESULTS During the study period, 53 patients underwent LT for either PH (n = 27), or IH (26). Cohort had mean age 58.5 years old (IQR, 47.0-63.0), body mass index (BMI) 25.9 (IQR, 22.9-30.0) kg/m2, and mean biologic MELD 9 (IQR, 7-17). Most frequent etiology was PSC (n = 12, 22.6%). Forty-nine patients (92.5%) received neoadjuvant therapy, including systemic (n = 48, 90.6%) and locoregional therapy (LRT) (n = 22, 41.5%), to which PH tumors were both most and least responsive (P = .03). On explant pathology, tumor were a median size of 3.5 cm and lympho-vascular invasion (LVI) was present in 13 (24.5%) cases. Median follow-up post-transplant was 910 days (IQR, 407-1509). Probabilities of OS and RFS at 3-years post-LT were 69.2% (95% CI, 56.9%-84.2%) and 57.4% (95% CI, 43.7%-75.4%). In multivariable analysis, OS was associated with tumor type and LVI, and RFS with age, BMI, PSC and LRT. After a median post-LT period of 38 days (IQR, 27-79.5), 39 (71.7%) patients started mTOR inhibition with lowered tacrolimus goal. Cox proportional hazard model showed significant association of OS with mTOR inhibition, though this was not validated by a time-dependent co-variate approach. CONCLUSIONS In this single center cohort of CCA, post-LT outcomes were significantly greater for patients with IH tumors and no LVI. Immunosuppression with mTOR inhibition was not consistently associated with outcomes.
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Affiliation(s)
- Samar Semaan
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Ashton A Connor
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY
| | - Ashish Saharia
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY
| | - Sudha Kodali
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX; Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Ahmed Elaileh
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Khush Patel
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Nadine Soliman
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Tamneet Basra
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - David W Victor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX; Department of Medicine, Weill Cornell Medical College, New York, NY
| | | | - Yee Lee Cheah
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Mark J Hobeika
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY
| | - Constance M Mobley
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY; Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Sadhna Dhingra
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX
| | - Mary R Schwartz
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX
| | - Anaum Maqsood
- Division of Medical Oncology, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Kirk Heyne
- Department of Medicine, Weill Cornell Medical College, New York, NY; Division of Medical Oncology, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Maen Abdelrahim
- Department of Medicine, Weill Cornell Medical College, New York, NY; Division of Medical Oncology, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Xian C Li
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Milind Javle
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - A Osama Gaber
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY
| | - R Mark Ghobrial
- Department of Surgery, Houston Methodist Hospital, Houston, TX; Department of Surgery, Weill Cornell Medical College, New York, NY.
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2
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Kodali S, Brombosz EW, Abdelrahim M, Mobley CM. The importance of equity in transplant oncology. Curr Opin Organ Transplant 2025; 30:21-29. [PMID: 39422605 DOI: 10.1097/mot.0000000000001183] [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: 10/19/2024]
Abstract
PURPOSE OF REVIEW Transplant oncology encompasses and utilizes liver transplantation (LT) in combination with other aspects of cancer care to offer improved long-term outcomes for patients with liver cancer, but not all patients have equal access and ability to undergo LT. Social determinants of health may negatively impact a patient's ability to receive liver-related oncologic care, including LT. This review highlights recent work exposing gaps in access to LT, including transplant oncology, and interventions to ameliorate these disparities. RECENT FINDINGS Members of racial and ethnic minorities and indigenous groups, females, socioeconomically disadvantaged persons, and patients from rural areas are less likely to undergo LT. Recent studies have also described programs that have successfully mitigated some of the barriers in access to transplant oncology that these patients experience, including targeted outreach programs and access to virtual healthcare. SUMMARY Disparities in access to LT for liver cancer are increasingly well described, but additional research is needed to find effective ways to ameliorate these differences.
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Affiliation(s)
- Sudha Kodali
- JC Walter Jr Transplant Center and Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Medicine, Houston Methodist Hospital, Houston, Texas
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | | | - Maen Abdelrahim
- JC Walter Jr Transplant Center and Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Medicine, Houston Methodist Hospital, Houston, Texas
- Department of Medicine, Weill Cornell Medical College, New York, New York
- Neal Cancer Center
| | - Constance M Mobley
- JC Walter Jr Transplant Center and Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Neal Cancer Center
- Department of Surgery, Houston Methodist Hospital, Houston, Texas
- Department of Surgery, Weill Cornell Medical College, New York, New York, USA
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3
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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4
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De Abreu Neto IP, Pugliese V, Massarollo PCB, Benini BB, Marta MMM, Takenaka VS, Monteiro F, Pessoa JLE, De Azevedo Neto RS, Gonzalez AM. Retrospective comparative analyses of liver transplantation for intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma versus hepatocellular carcinoma in Brazil. HPB (Oxford) 2025:S1365-182X(25)00024-3. [PMID: 39890516 DOI: 10.1016/j.hpb.2025.01.008] [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: 08/16/2024] [Revised: 01/05/2025] [Accepted: 01/12/2025] [Indexed: 02/03/2025]
Abstract
BACKGROUND Despite the growing interest in liver transplantation for cholangiocarcinomas (CCA), conclusive evidence is lacking. We sought to evaluate the outcomes of liver transplantation for intrahepatic cholangiocarcinoma in Brazil. METHODS Retrospective database analysis of patients undergoing liver transplantation for hepatocellular carcinoma (HCC) within Milan criteria in São Paulo, Brazil. Anatomopathological examination of the explanted liver with the presence of intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) comprised the study group (50 patients). They were compared to a 1:3 HCC-matched cohort. RESULTS Study group had lower survival rates than HCC controls (survival at 1, 3, and 5 years, 70.0 %, 57.5 %, and 57.5 % versus 78.7 %, 71.4 %, and 66.6 %, p = 0.019). 5-year survival rates of the control group, cHCC-CCA, and iCCA group were 66.6 %, 59.6 %, and 50.0 % (p = 0.017). There was no statistically significant difference in survival for study group patients with tumors up to 3 cm compared to their controls (p = 0.086). DISCUSSION Patients with CCA had worse outcomes after liver transplantation than those with HCC. Interesting results were found in the more individualized analyses, but because of the limited number of patients, caution should be taken when analyzing them.
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Affiliation(s)
| | - Vincenzo Pugliese
- Liver Transplantation Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, BR 05403-010
| | - Paulo C B Massarollo
- Department of Surgery, Faculdade de Medicina da Universidade de São Paulo, BR 01246-903
| | - Bárbara B Benini
- Liver Transplantation Unit, São Paulo Federal University, BR 04023-062
| | - Mirella M M Marta
- Liver Transplantation Unit, São Paulo Federal University, BR 04023-062
| | | | - Francisco Monteiro
- São Paulo State Transplant System, São Paulo Health Secretariat, BR 05403-000
| | - João Luis E Pessoa
- São Paulo State Transplant System, São Paulo Health Secretariat, BR 05403-000
| | - Raymundo S De Azevedo Neto
- Pathology Department, Faculdade de Medicina da Universidade de São Paulo, BR 01246-903, São Paulo, Brazil
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5
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Gringeri E, Furlanetto A, Billato I, Cescon M, De Carlis L, Mazzaferro V, Romagnoli R, De Simone P, Vivarelli M, Di Benedetto F, Ravaioli M, Lauterio A, Sposito C, Patrono D, Ghinolfi D, Moccheggiani F, Di Sandro S, D'Amico FE, Lanari J, Gambato M, Trapani S, Bergamo F, Cardillo M, Burra P, Cillo U. The Italian experience on liver transplantation for unresectable peri-hilar cholangiocarcinoma: a national survey and future perspectives. Updates Surg 2024; 76:2505-2513. [PMID: 39210194 DOI: 10.1007/s13304-024-01889-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 05/18/2024] [Indexed: 09/04/2024]
Abstract
Liver transplantation (LT) was considered an ineffective treatment for perihilar cholangiocarcinoma (pCCA) until the successful experience of the Mayo Clinic, proposing a protocol with strict inclusion criteria and neoadjuvant radio-chemotherapy. Since 2015, pCCA is considered an indication for LT in Italy only in the context of controlled prospective studies. We performed a survey among the 22 Italian Liver Transplant Centers to assess the results of LT for pCCA. Eight centers reported 53 cases from 1986 to 2021 (Bologna 12, Padova 10, Niguarda 10, Milano Tumori 8, Torino 5, Pisa 4, Ancona 2, Modena 2). Patients were divided according to whether they recieved neoadjuvant radio-chemotherapy (Group 1, 25 cases) or not (Group 2, 28 cases). Eleven patients were transplanted without neoadjuvant treatment after 2015. Overall survival at 1, 3 and 5 years was 83.8%, 56.6% and 50.6% in Group 1 and 72.4%, 41.4% and 35.5% in Gropu 2 (p = 0.13). Recurrence-free survival at 1, 3, and 5 years was 91.2%, 61.1% and 47.2% in Group 1 and 58.2%, 42.2%, and 36.1% in Group 2 (p = 0.16). A competing risk regression analysis showed a 5-year risk of cancer-related death of 19% for patients in Group 1 against 62.3% in Group 2, with a hazard ratio of 0.31 (95%CI [0.10-0.98], p 0.047). This survey promoted a discussion about the limitations of the Mayo protocol and set the basis for the adoption of a new nationwide protocol (LITHALICA-NCT06125769), having the same inclusion criteria but proposing standard of care chemotherapy as neoadjuvant regimen.
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Affiliation(s)
- Enrico Gringeri
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy.
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
| | - Alessandro Furlanetto
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Ilaria Billato
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Matteo Cescon
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, 20162, Milan, Italy
| | - Vincenzo Mazzaferro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori Di Milano, Milan, Italy
| | - Renato Romagnoli
- Liver Transplant Center, General Surgery 2, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| | - Paolo De Simone
- Liver Transplant Program, University of Pisa Medical School Hospital, Pisa, Italy
| | - Marco Vivarelli
- Hepato-Pancreato-Biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126, Ancona, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena "Policlinico", University of Modena and Reggio Emilia, Modena, Italy
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, 20162, Milan, Italy
| | - Carlo Sposito
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori Di Milano, Milan, Italy
| | - Damiano Patrono
- Liver Transplant Center, General Surgery 2, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| | - Davide Ghinolfi
- Liver Transplant Program, University of Pisa Medical School Hospital, Pisa, Italy
| | - Federico Moccheggiani
- Hepato-Pancreato-Biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126, Ancona, Italy
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena "Policlinico", University of Modena and Reggio Emilia, Modena, Italy
| | - Francesco Enrico D'Amico
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Jacopo Lanari
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Padova University, Padua, Italy
| | - Silvia Trapani
- Italian National Transplant Center-Istituto Superiore Di Sanità, Rome, Italy
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Massimo Cardillo
- Italian National Transplant Center-Istituto Superiore Di Sanità, Rome, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padova University, Padua, Italy
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Umberto Cillo
- General Surgery 2, Hepato-biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
- Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
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Neuzillet C, Decraecker M, Larrue H, Ntanda-Nwandji LC, Barbier L, Barge S, Belle A, Chagneau C, Edeline J, Guettier C, Huguet F, Jacques J, Le Bail B, Leblanc S, Lewin M, Malka D, Ronot M, Vendrely V, Vibert É, Bureau C, Bourliere M, Ganne-Carrie N, Blanc JF. Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF). Liver Int 2024; 44:2517-2537. [PMID: 38967424 DOI: 10.1111/liv.15948] [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: 12/29/2023] [Revised: 03/13/2024] [Accepted: 04/11/2024] [Indexed: 07/06/2024]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.
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Affiliation(s)
- Cindy Neuzillet
- GI Oncology, Medical Oncology Department, Institut Curie, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France
| | - Marie Decraecker
- Oncology Digestive Unit, INSERM U1312, University Hospital of Bordeaux, Bordeaux, France
| | - Hélène Larrue
- Department of Hepatology, University Hospital, Toulouse III-Paul Sabatier University, Toulouse, France
| | | | - Louise Barbier
- New Zealand Liver Transplant Unit and HPB Surgery, Te Toka Tumai, University of Auckland, Auckland, New Zealand
| | - Sandrine Barge
- Centre Hospitalier Intercommunal Créteil-CHI Créteil, Créteil, France
| | - Arthur Belle
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | | | - Julien Edeline
- Department of Medical Oncology, CLCC Eugène Marquis, COSS-UMR S1242, INSERM, Univ Rennes, Rennes, France
| | - Catherine Guettier
- Department of Pathology, APHP University Paris Saclay, Hôpital Bicetre, Paris, France
| | - Florence Huguet
- Radiation Oncology Department, Tenon Hospital, APHP-Sorbonne University, Paris, France
| | | | - Brigitte Le Bail
- Pathology Department, University Hospital of Bordeaux, Bordeaux, France
| | - Sarah Leblanc
- Gastroenterology Department, Private Hospital Jean Mermoz, Ramsay Santé, Lyon, France
| | - Maïté Lewin
- Service de Radiologie, AP-HP-Université Paris Saclay Hôpital Paul Brousse, Villejuif, France
| | - David Malka
- Medical Oncology Department, Institut Mutualiste Monsouris, Paris, France
| | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, APHP Nord Clichy, University Paris Cité, CRI UMR, Paris, France
| | | | - Éric Vibert
- Centre Hepato-Biliaire, AP-HP-Université Paris Saclay Hôpital Paul Brousse, Villejuif, France
| | - Christophe Bureau
- Department of Hepatology, University Hospital, Toulouse III-Paul Sabatier University, Toulouse, France
| | | | | | - Jean-Frédéric Blanc
- Oncology Digestive Unit, INSERM U1312, University Hospital of Bordeaux, Bordeaux, France
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7
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Patrono D, De Stefano N, Romagnoli R. Liver transplantation for tumor entities. Curr Opin Organ Transplant 2024; 29:255-265. [PMID: 38716718 DOI: 10.1097/mot.0000000000001149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2024]
Abstract
PURPOSE OF REVIEW Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology. RECENT FINDINGS Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection. SUMMARY While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.
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Affiliation(s)
- Damiano Patrono
- General Surgery 2U - Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino - University of Turin, Turin, Italy
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8
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Pang NQ, Chan ACY, Kow AWC. Trends of liver transplantation in Asia. Updates Surg 2024:10.1007/s13304-024-01924-1. [PMID: 39046632 DOI: 10.1007/s13304-024-01924-1] [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: 03/20/2024] [Accepted: 06/18/2024] [Indexed: 07/25/2024]
Abstract
Liver transplantation (LT) in Asia started comparatively early in 1964, just 1 year after Starzl's trail-blazing first attempt. Despite the quick start, LT was slow to develop in this region. Limited access to universal healthcare, lack of public understanding and support as well as the absence of strong legislation, on a backdrop of a wide range of diverse social, religious, economic and cultural background are all contributory factors. Through strong administrative efforts, the number of DDLTs in selected Asian countries has been slowly rising in recent years. However, Asians are generally still less likely to donate organs than Caucasians after death. The strong demand for LT with limited access to deceased organs has, therefore, led to constant need for innovation in LT this region, with the pioneering of various LDLT techniques and safe expansion of donor pool being driven primarily by Asian centers. Familiarity and the development of technical expertise in donor surgery have also resulted in Asian centers repeatedly pushing the boundaries on minimally invasive donor and recipient surgery. In this article, we focus on the past and present states of LT in Asia and explore the future trends of LT in this region.
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Affiliation(s)
- Ning Qi Pang
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore
| | - Albert C Y Chan
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore.
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore.
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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9
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Lai Q, Parisse S, Ginanni Corradini S, Ferri F, Kolovou K, Campagna P, Melandro F, Mennini G, Merli M, Rossi M. Evolution of transplant oncology indications: a single-institution experience over 40 years. Updates Surg 2024; 76:911-921. [PMID: 38589745 PMCID: PMC11130028 DOI: 10.1007/s13304-024-01827-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/06/2024] [Indexed: 04/10/2024]
Abstract
Liver transplantation (LT) for uncommon tumoral indications has changed across the decades, with impaired results reported in the first historical series mainly for non-tumoral-related causes. Recently, renewed interest in liver transplant oncology has been reported. The study aims to analyze a mono-center experience exploring the evolution and the impact on patient survival of LT in uncommon tumoral indications. A retrospective analysis of 851 LT performed during 1982-2023 was investigated. 33/851 (3.9%) uncommon tumoral indications were reported: hepatocellular carcinoma (HCC) on non-cirrhotic liver (n = 14), peri-hilar (phCCA) (n = 8) and intrahepatic cholangiocarcinoma (i-CCA) (n = 3), metastatic disease (n = 4), hepatic hemangioendothelioma (n = 2), and benign tumor (n = 2). Uncommon tumoral indications were mainly transplanted during the period 1982-1989, with a complete disappearance after the year 2000 and a slight rise in the last years. Poor outcomes were reported: 5-year survival rates were 28.6%, 25.0%, 0%, and 0% in the case of HCC on non-cirrhotic liver, phCCA, i-CCA, and metastases, respectively. However, the cause of patient death was often related to non-tumoral conditions. LT for uncommon oncological diseases has increased worldwide in recent decades. Historical series report poor survival outcomes despite more recent data showing promising results. Hence, the decision to transplant these patients should be under the risk and overall benefit of the patient. The results of the ongoing protocol studies are expected to confirm the validity of the unconventional tumor indications.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy.
| | - Simona Parisse
- Department of Translational and Precision Medicine, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Stefano Ginanni Corradini
- Department of Translational and Precision Medicine, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Flaminia Ferri
- Department of Translational and Precision Medicine, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Konstantina Kolovou
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Pasquale Campagna
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Fabio Melandro
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Rome, Italy
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10
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Esmail A, Badheeb M, Alnahar B, Almiqlash B, Sakr Y, Khasawneh B, Al-Najjar E, Al-Rawi H, Abudayyeh A, Rayyan Y, Abdelrahim M. Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation. Cancers (Basel) 2024; 16:1946. [PMID: 38893067 PMCID: PMC11171350 DOI: 10.3390/cancers16111946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06605, USA
| | - Batool Alnahar
- College of Medicine, Almaarefa University, Riyadh 13713, Saudi Arabia
| | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Bayan Khasawneh
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Hadeel Al-Rawi
- Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
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11
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Howell TC, Rhodin KE, Shaw B, Bao J, Kanu E, Masoud S, Bartholomew AJ, Gao Q, Anwar IJ, Ladowski JM, Nussbaum DP, Blazer DG, Zani S, Allen PJ, Barbas AS, Lidsky ME. Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma. J Gastrointest Surg 2024; 28:738-745. [PMID: 38704208 DOI: 10.1016/j.gassur.2024.02.029] [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: 06/27/2023] [Revised: 11/10/2023] [Accepted: 02/17/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.
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Affiliation(s)
- Thomas Clark Howell
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Kristen E Rhodin
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Brian Shaw
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Jiayin Bao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Elishama Kanu
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabran Masoud
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Alex J Bartholomew
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Qimeng Gao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Imran J Anwar
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Joseph M Ladowski
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Daniel P Nussbaum
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Dan G Blazer
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States.
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12
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Guba M, Werner J. [Liver transplantation for treatment of nonresectable primary and secondary liver malignancies : Hepatocellular and cholangiocellular carcinomas and colorectal liver metastases]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:268-273. [PMID: 38329517 DOI: 10.1007/s00104-024-02036-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/10/2024] [Indexed: 02/09/2024]
Abstract
BACKGROUND With the increasing efficacy of systemic therapy, liver transplantation plays an important role not only for hepatocellular carcinoma (HCC) but also for nonresectable intrahepatic cholangiocellular carcinoma (iCC), perihilar cholangiocellular carcinoma (phCC) and colorectal liver metastases (CRLM). AIM To review the current state of knowledge regarding the indications, patient selection and expected outcomes of liver transplantation for HCC, iCC, phCC and CRLM. RESULTS When combined with neoadjuvant locoregional therapy (LRT) and/or systemic therapy, patients with nonresectable HCC, iCC, pCC and CRLM confined to the liver can be successfully transplanted with 5‑year survival rates exceeding 65%. The key to success is strict patient selection, which includes oncogenetic (e.g., BRAFV600E mutation status) and clinical criteria indicative of individual tumor biology (tumor markers: alpha-fetoprotein, AFP/carbohydrate antigen 19‑9, CA19-9/carcinoembryonic antigen, CEA, stable response to neoadjuvant therapy) in addition to morphometric criteria. CONCLUSION Liver transplantation offers the possibility of curative treatment even for nonresectable hepatic malignancies. A major limitation of this treatment is the lack of donor organs. Crucial for success is patient selection based on individual tumor biology.
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Affiliation(s)
- Markus Guba
- Klinik für Allgemein‑, Viszeral-, und Transplantationschirurgie, LMU München, Marchioninistraße 15, 81377, München, Deutschland.
| | - Jens Werner
- Klinik für Allgemein‑, Viszeral-, und Transplantationschirurgie, LMU München, Marchioninistraße 15, 81377, München, Deutschland
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13
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Andraus W, Tustumi F, Santana AC, Pinheiro RSN, Waisberg DR, Lopes LD, Arantes RM, Santos VR, de Martino RB, D'Albuquerque LAC. Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review. Hepatobiliary Pancreat Dis Int 2024; 23:139-145. [PMID: 38310060 DOI: 10.1016/j.hbpd.2024.01.003] [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: 08/16/2023] [Accepted: 01/19/2024] [Indexed: 02/05/2024]
Abstract
BACKGROUND Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. DATA SOURCES The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. RESULTS Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. CONCLUSIONS phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.
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Affiliation(s)
- Wellington Andraus
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil.
| | - Francisco Tustumi
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Alexandre Chagas Santana
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | | | - Daniel Reis Waisberg
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Liliana Ducatti Lopes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Rubens Macedo Arantes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Vinicius Rocha Santos
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
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14
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Battistella S, Grasso M, Catanzaro E, D’Arcangelo F, Corrà G, Germani G, Senzolo M, Zanetto A, Ferrarese A, Gambato M, Burra P, Russo FP. Evolution of Liver Transplantation Indications: Expanding Horizons. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:412. [PMID: 38541138 PMCID: PMC10972065 DOI: 10.3390/medicina60030412] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 01/03/2025]
Abstract
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy; (S.B.); (E.C.); (F.D.); (G.C.); (G.G.); (M.S.); (A.Z.); (A.F.); (M.G.); (P.B.)
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15
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Pratt CG, Whitrock JN, Shah SA, Fong ZV. How to Determine Unresectability in Hilar Cholangiocarcinoma. Surg Clin North Am 2024; 104:197-214. [PMID: 37953036 DOI: 10.1016/j.suc.2023.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Hilar cholangiocarcinoma is considered a biologically aggressive disease for which surgical resection remains the only curative treatment. Preoperative evaluation for resectability is challenging given tumor proximity to the porta hepatis, but minimal benefit and increased morbidity precludes recommendation for margin positive resection. This article reviews the determination of unresectability in hilar cholangiocarcinoma through discussion of the preoperative assessment, the intraoperative assessment, and key steps of surgical resection, as well as treatment options for unresectable tumors. Overall, evaluating patients preoperatively for resectability requires a multidisciplinary, holistic, and individualized approach to accurately determine resectability and optimize clinical outcomes for patients with hilar cholangiocarcinoma.
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Affiliation(s)
- Catherine G Pratt
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA. https://twitter.com/CPrattMD
| | - Jenna N Whitrock
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA. https://twitter.com/JennaWhitrockMD
| | - Shimul A Shah
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA; Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, MSB 2006C, ML 0519, Cincinnati, OH 45267-0558, USA. https://twitter.com/shimulshah73
| | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Mayo Clinic College of Medicine, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA.
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16
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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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17
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [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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18
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie biliärer Karzinome“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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19
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Zhan PC, Yang T, Zhang Y, Liu KY, Li Z, Zhang YY, Liu X, Liu NN, Wang HX, Shang B, Chen Y, Jiang HY, Zhao XT, Shao JH, Chen Z, Wang XD, Wang K, Gao JB, Lyu PJ. Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study. Eur Radiol 2024; 34:1280-1291. [PMID: 37589900 DOI: 10.1007/s00330-023-10108-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 06/07/2023] [Accepted: 06/29/2023] [Indexed: 08/18/2023]
Abstract
OBJECTIVES To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.
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Affiliation(s)
- Peng-Chao Zhan
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Ting Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuan Zhang
- Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Ke-Yan Liu
- Zhengzhou University Medical College, Zhengzhou, 450052, China
| | - Zhen Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Yu-Yuan Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xing Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Na-Na Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Hui-Xia Wang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Bo Shang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Yan Chen
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China
| | - Han-Yu Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiang-Tian Zhao
- Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Jing-Hai Shao
- Department of Radiology, He Nan Sui Xian People's Hospital, Shangqiu, 476000, China
| | - Zhe Chen
- Department of Radiology, People's Hospital of Tanghe, Nanyang, 473000, China
| | - Xin-Dong Wang
- Department of Radiology, People's Hospital of Tanghe, Nanyang, 473000, China
| | - Kang Wang
- Department of Radiology, People's Hospital of Tanghe, Nanyang, 473000, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China.
| | - Pei-Jie Lyu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, ZhengzhouZhengzhou, 450052, China.
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20
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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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21
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie des Hepatozellulären Karzinoms“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e67-e161. [PMID: 38195102 DOI: 10.1055/a-2189-6353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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22
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Rushbrook SM, Kendall TJ, Zen Y, Albazaz R, Manoharan P, Pereira SP, Sturgess R, Davidson BR, Malik HZ, Manas D, Heaton N, Prasad KR, Bridgewater J, Valle JW, Goody R, Hawkins M, Prentice W, Morement H, Walmsley M, Khan SA. British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma. Gut 2023; 73:16-46. [PMID: 37770126 PMCID: PMC10715509 DOI: 10.1136/gutjnl-2023-330029] [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: 04/06/2023] [Accepted: 09/05/2023] [Indexed: 10/03/2023]
Abstract
These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.
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Affiliation(s)
- Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | - Timothy James Kendall
- Division of Pathology, University of Edinburgh, Edinburgh, UK
- University of Edinburgh MRC Centre for Inflammation Research, Edinburgh, UK
| | - Yoh Zen
- Department of Pathology, King's College London, London, UK
| | - Raneem Albazaz
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | | | - Richard Sturgess
- Digestive Diseases Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, London, UK
| | - Hassan Z Malik
- Department of Surgery, University Hospital Aintree, Liverpool, UK
| | - Derek Manas
- Department of Surgery, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
| | - Nigel Heaton
- Department of Hepatobiliary and Pancreatic Surgery, King's College London, London, UK
| | - K Raj Prasad
- John Goligher Colorectal Unit, St. James University Hospital, Leeds, UK
| | - John Bridgewater
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK
| | - Rebecca Goody
- Department of Oncology, St James's University Hospital, Leeds, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | - Wendy Prentice
- King's College Hospital NHS Foundation Trust, London, UK
| | | | | | - Shahid A Khan
- Hepatology and Gastroenterology Section, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Imperial College Healthcare NHS Trust, London, UK
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23
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Ruff SM, Cloyd JM, Pawlik TM. Annals of Surgical Oncology Practice Guidelines Series: Management of Primary Liver and Biliary Tract Cancers. Ann Surg Oncol 2023; 30:7935-7949. [PMID: 37691030 DOI: 10.1245/s10434-023-14255-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 08/22/2023] [Indexed: 09/12/2023]
Abstract
Primary cancers of the liver and biliary tract are rare and aggressive tumors that often present with locally advanced or metastatic disease. For patients with localized disease amenable to resection, surgery typically offers the best chance at curative-intent therapy. Unfortunately, the incidence of recurrence even after curative-intent surgery remains high. In turn, patients with hepatobiliary cancers commonly require multimodality therapy including a combination of resection, systemic therapy (i.e., targeted therapy, cytotoxic chemotherapy, immunotherapy), and/or loco-regional therapies. With advancements in the field, it is crucial for surgical oncologists to remain updated on the latest guidelines and recommendations for surgical management and optimal patient selection. Given the complex and evolving nature of treatment, this report highlights the latest practice guidelines for the surgical management of hepatobiliary cancers.
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Affiliation(s)
- Samantha M Ruff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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24
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Kawano F, Yoshioka R, Ichida H, Mise Y, Saiura A. Essential updates 2021/2022: Update in surgical strategy for perihilar cholangiocarcinoma. Ann Gastroenterol Surg 2023; 7:848-855. [PMID: 37927920 PMCID: PMC10623956 DOI: 10.1002/ags3.12734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 07/21/2023] [Accepted: 08/10/2023] [Indexed: 11/07/2023] Open
Abstract
Resection is the only potential curative treatment for perihilar cholangiocarcinoma (PHC); however, complete resection is often technically challenging due to the anatomical location. Various innovative approaches and procedures were invented to circumvent this limitation but the rates of postoperative morbidity (20%-78%) and mortality (2%-15%) are still high. In patients diagnosed with resectable PHC, deliberate and coordinated preoperative workup and optimization of the patient and future liver remnant are crucial. Biliary drainage is recommended to relieve obstructive jaundice and optimize the clinical condition before liver resection. Biliary drainage for PHC can be performed either by endoscopic biliary drainage or percutaneous transhepatic biliary drainage. To date there is no consensus about which method is preferred. The volumetric assessment of the future remnant liver volume and optimization mainly using portal vein embolization is the gold standard in the management of the risk to develop post hepatectomy liver failure. The improvement of systemic chemotherapy has contributed to prolong the survival not only in patients with unresectable PHC but also in patients undergoing curative surgery. In this article, we review the literature and discuss the current surgical treatment of PHC.
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Affiliation(s)
- Fumihiro Kawano
- Department of Hepatobiliary‐Pancreatic SurgeryJuntendo University Graduate School of MedicineHongo, TokyoJapan
| | - Ryuji Yoshioka
- Department of Hepatobiliary‐Pancreatic SurgeryJuntendo University Graduate School of MedicineHongo, TokyoJapan
| | - Hirofumi Ichida
- Department of Hepatobiliary‐Pancreatic SurgeryJuntendo University Graduate School of MedicineHongo, TokyoJapan
| | - Yoshihiro Mise
- Department of Hepatobiliary‐Pancreatic SurgeryJuntendo University Graduate School of MedicineHongo, TokyoJapan
| | - Akio Saiura
- Department of Hepatobiliary‐Pancreatic SurgeryJuntendo University Graduate School of MedicineHongo, TokyoJapan
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25
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Ersan V, Usta S, Aydin C, Carr BI, Karatoprak S, Yilmaz S. Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma. Acta Chir Belg 2023; 123:489-496. [PMID: 35549649 DOI: 10.1080/00015458.2022.2078030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 05/11/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. METHODS Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. RESULTS Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. CONCLUSION It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.
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Affiliation(s)
- Veysel Ersan
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
| | - Sertac Usta
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
| | - Cemalettin Aydin
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
| | - Brian I Carr
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
| | - Sinan Karatoprak
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
| | - Sezai Yilmaz
- Inonu University, Liver Transplantation Institute, Malatya, Turkey
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26
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Jena SS, Mehta NN, Nundy S. Surgical management of hilar cholangiocarcinoma: Controversies and recommendations. Ann Hepatobiliary Pancreat Surg 2023; 27:227-240. [PMID: 37408334 PMCID: PMC10472117 DOI: 10.14701/ahbps.23-028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/12/2023] [Accepted: 04/17/2023] [Indexed: 07/07/2023] Open
Abstract
Hilar cholangiocarcinomas are highly aggressive malignancies. They are usually at an advanced stage at initial presentation. Surgical resection with negative margins is the standard of management. It provides the only chance of cure. Liver transplantation has increased the number of 'curative' procedures for cases previously considered to be unresectable. Meticulous and thorough preoperative planning is required to prevent fatal post-operative complications. Extended resection procedures, including hepatic trisectionectomy for Bismuth type IV tumors, hepatopancreaticoduodenectomy for tumors with extensive longitudinal spread, and combined vascular resection with reconstruction for tumors involving hepatic vascular structures, are challenging procedures with surgical indications expanded. Liver transplantation after the standardization of a neoadjuvant protocol described by the Mayo Clinic has increased the number of patients who can undergo operation.
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Affiliation(s)
- Suvendu Sekhar Jena
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Naimish N Mehta
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Samiran Nundy
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
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27
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Shannon AH, Ruff SM, Schenk AD, Washburn K, Pawlik TM. Updates and Expert Opinions on Liver Transplantation for Gastrointestinal Malignancies. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1290. [PMID: 37512101 PMCID: PMC10383519 DOI: 10.3390/medicina59071290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/12/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023]
Abstract
Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) of the liver. Although there are established criteria for LT in HCC, evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.
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28
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Keltner SJ, Hallemeier C, Wang K, Tao R, Shah S, Heimbach J, Kharofa JR. Neoadjuvant Therapy Regimens for Hilar Cholangiocarcinoma Before Liver Transplant. Am J Clin Oncol 2023; 46:276-278. [PMID: 37036238 DOI: 10.1097/coc.0000000000001002] [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: 04/11/2023]
Abstract
OBJECTIVES Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA. METHODS A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method. RESULTS Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines. CONCLUSIONS These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices.
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Affiliation(s)
| | | | - Kyle Wang
- University of Cincinnati Cancer Center
| | - Randa Tao
- University of Utah Huntsman Cancer Institute, Salt Lake City, UT
| | - Shimul Shah
- University of Cincinnati Medical Center/College of Medicine, Cincinnati, OH
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29
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Borakati A, Froghi F, Bhogal RH, Mavroeidis VK. Liver transplantation in the management of cholangiocarcinoma: Evolution and contemporary advances. World J Gastroenterol 2023; 29:1969-1981. [PMID: 37155529 PMCID: PMC10122785 DOI: 10.3748/wjg.v29.i13.1969] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/10/2023] [Accepted: 03/21/2023] [Indexed: 04/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the biliary epithelium. It may occur at any location along the biliary tree with the perihilar area being the most common. Prognosis is poor with 5-year overall survival at less than 10%, typically due to unresectable disease at presentation. Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours, but is frequently not possible due to locally advanced disease. On the other hand, orthotopic liver transplantation (LT) allows for a radical and potentially curative resection for these patients, but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes. In patients with perihilar CCA, within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT, excellent results have been achieved in the last decades, resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience. However, in intrahepatic CCA, the role of LT remains controversial and owing to dismal previous results it is not an accepted indication. Nevertheless, more recent studies have demonstrated favourable results with LT in early intrahepatic CCA, indicating that, under defined criteria, its role may increase in the future. This review highlights the history and contemporary advances of LT in CCA, with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.
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Affiliation(s)
- Aditya Borakati
- Department of HPB and Liver Transplantation Surgery, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, United Kingdom
| | - Farid Froghi
- Department of HPB and Liver Transplantation Surgery, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, United Kingdom
| | - Ricky H Bhogal
- Department of Academic Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
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30
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Bitzer M, Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère CL, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e92-e156. [PMID: 37040776 DOI: 10.1055/a-2026-1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | | | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschrirugie, Eberhard-Karls Universität, Tübingen
| | | | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Quaresima S, Melandro F, Giovanardi F, Shah K, De Peppo V, Mennini G, Ghinolfi D, Limkemann A, Pawlik TM, Lai Q. New Insights in the Setting of Transplant Oncology. Medicina (B Aires) 2023; 59:medicina59030568. [PMID: 36984569 PMCID: PMC10058845 DOI: 10.3390/medicina59030568] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT’s impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.
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Affiliation(s)
- Silvia Quaresima
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
| | - Fabio Melandro
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Giovanardi
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
| | - Kejal Shah
- Department of Surgery, Division of Surgical Oncology, James Cancer Center, The Ohio State University, Columbus, OH 43210, USA
| | - Valerio De Peppo
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
| | - Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Ashley Limkemann
- Department of Surgery, Division of Surgical Oncology, James Cancer Center, The Ohio State University, Columbus, OH 43210, USA
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, James Cancer Center, The Ohio State University, Columbus, OH 43210, USA
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy
- Correspondence: ; Tel.: +39-3493020126; Fax: +39-06499701
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Patrono D, Colli F, Colangelo M, De Stefano N, Apostu AL, Mazza E, Catalano S, Rizza G, Mirabella S, Romagnoli R. How Can Machine Perfusion Change the Paradigm of Liver Transplantation for Patients with Perihilar Cholangiocarcinoma? J Clin Med 2023; 12:jcm12052026. [PMID: 36902813 PMCID: PMC10004136 DOI: 10.3390/jcm12052026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.
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Villard C, Friis-Liby I, Rorsman F, Said K, Warnqvist A, Cornillet M, Kechagias S, Nyhlin N, Werner M, Janczewska I, Hagström T, Nilsson E, Bergquist A. Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis. J Hepatol 2023; 78:604-613. [PMID: 36410555 DOI: 10.1016/j.jhep.2022.11.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND & AIMS The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort. METHODS In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression. RESULTS Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n = 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01). CONCLUSION In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted. IMPACT AND IMPLICATIONS A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.
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Affiliation(s)
- Christina Villard
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | | | - Fredrik Rorsman
- Department of Hepatology, Akademiska University Hospital, Uppsala, Sweden
| | - Karouk Said
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Warnqvist
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Martin Cornillet
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Stergios Kechagias
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Nils Nyhlin
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Mårten Werner
- Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | | | - Therese Hagström
- Department of Gastroenterology, Stockholm South General Hospital, Stockholm, Sweden
| | - Emma Nilsson
- Gastroenterology Clinic, Skåne University Hospital, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
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Qin T, Wang M, Zhang H, Li J, Deng X, Zhang Y, Zhao W, Fan Y, Li D, Chen X, Feng Y, Zhu S, Xing Z, Yu G, Xu J, Xie J, Dou C, Ma H, Liu G, Shao Y, Chen W, Xu S, Liu J, Liu J, Yin X, Qin R. The Long-Term Outcome of Laparoscopic Resection for Perihilar Cholangiocarcinoma Compared with the Open Approach: A Real-World Multicentric Analysis. Ann Surg Oncol 2023; 30:1366-1378. [PMID: 36273058 PMCID: PMC9589740 DOI: 10.1245/s10434-022-12647-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 09/22/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The aim of this study was to compare the short- and long-term outcomes of laparoscopic surgery (LS) and open surgery (OP) for perihilar cholangiocarcinoma (PHC) using a large real-world dataset in China. METHODS Data of patients with PHC who underwent LS and OP from January 2013 to October 2018, across 10 centers in China, were extracted from medical records. A comparative analysis was performed before and after propensity score matching (PSM) in the LS and OP groups and within the study subgroups. The Cox proportional hazards mixed-effects model was applied to estimate the risk factors for mortality, with center and year of operation as random effects. RESULTS A total of 467 patients with PHC were included, of whom 161 underwent LS and 306 underwent OP. Postoperative morbidity, such as hemorrhage, biliary fistula, abdominal abscess, and hepatic insufficiency, was similar between the LS and OP groups. The median overall survival (OS) was longer in the LS group than in the OP group (NA vs. 22 months; hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.02-1.39, p = 0.024). Among the matched datasets, OS was comparable between the LS and OP groups (NA vs. 35 months; HR 0.99, 95% CI 0.77-1.26, p = 0.915). The mixed-effect model identified that the surgical method was not associated with long-term outcomes and that LS and OP provided similar oncological outcomes. CONCLUSIONS Considering the comparable long-term prognosis and short-term outcomes of LS and OP, LS could be a technically feasible surgical method for PHC patients with all Bismuth-Corlett types of PHC.
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Affiliation(s)
- Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jingdong Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute of North Sichuan Medical College, Nanchong, China
| | - Xiaxing Deng
- Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhua Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310003, China
| | - Wenxing Zhao
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University Xuzhou, Jiangsu, China
| | - Ying Fan
- Department of the Second General Surgery, Sheng Jing Hospital of China Medical University, Liaoning, China
| | - Dewei Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xuemin Chen
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Suzhou, China
| | - Yechen Feng
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Siwei Zhu
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Zhongqiang Xing
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Guangsheng Yu
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shangdong, China
| | - Jian Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute of North Sichuan Medical College, Nanchong, China
| | - Junjie Xie
- Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changwei Dou
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310003, China
| | - Hongqin Ma
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University Xuzhou, Jiangsu, China
| | - Gangshan Liu
- Department of the Second General Surgery, Sheng Jing Hospital of China Medical University, Liaoning, China
| | - Yue Shao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Weibo Chen
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Suzhou, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Liu
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shangdong, China.
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
| | - Xinmin Yin
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Giovinazzo F, Pascale MM, Cardella F, Picarelli M, Molica S, Zotta F, Martullo A, Clarke G, Frongillo F, Grieco A, Agnes S. Current Perspectives in Liver Transplantation for Perihilar Cholangiocarcinoma. Curr Oncol 2023; 30:2942-2953. [PMID: 36975438 PMCID: PMC10047046 DOI: 10.3390/curroncol30030225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/17/2023] [Accepted: 01/30/2023] [Indexed: 03/05/2023] Open
Abstract
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are considered unresectable at the time of diagnosis or exploration. When resective surgery is deemed unfeasible, liver transplantation (LT) could be an effective alternative. The overall survival rates after LT at 1 and 3 years are 91% and 81%, respectively. The overall five-year survival rate after transplantation is 73% (79% for patients with underlying PSC and 63% for de novo pCCA). Multicenter case series reported a 5-year disease-free survival rate of ~65%. However, different protocols, including neoadjuvant therapy, have been proposed. The scarcity of organ availability represents a crucial limiting factor in recommending LT preferentially in treating pCCA. Living donor transplantations and marginal cadaveric allografts have proven to be exciting options to overcome organ shortage. Management of jaundice and cholangitis is still challenging for these patients and could impact LT listing. Whether to adopt surgical resection or LT as standard-of-care in pCCA is still a matter of debate, and more prospective studies are needed.
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Affiliation(s)
- Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Correspondence:
| | - Marco Maria Pascale
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, 80138 Naples, Italy
| | - Matteo Picarelli
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Serena Molica
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Zotta
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Annamaria Martullo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - George Clarke
- Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, UK
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Grieco
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Mauro E, Ferrer-Fàbrega J, Sauri T, Soler A, Cobo A, Burrel M, Iserte G, Forner A. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers (Basel) 2023; 15:1244. [PMID: 36831586 PMCID: PMC9953927 DOI: 10.3390/cancers15041244] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/03/2023] [Accepted: 02/11/2023] [Indexed: 02/18/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15-35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.
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Affiliation(s)
- Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
| | - Tamara Sauri
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Medical Oncology Department, ICMHO, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alexandre Soler
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Amparo Cobo
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Nuclear Medicine Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Department of Interventional Radiology, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Gemma Iserte
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
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Tchelebi LT, Jethwa KR, Levy AT, Anker CJ, Kennedy T, Grodstein E, Hallemeier CL, Jabbour SK, Kim E, Kumar R, Lee P, Small W, Williams VM, Sharma N, Russo S. American Radium Society (ARS) Appropriate Use Criteria (AUC) for Extrahepatic Cholangiocarcinoma. Am J Clin Oncol 2023; 46:73-84. [PMID: 36534388 PMCID: PMC9855763 DOI: 10.1097/coc.0000000000000969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.
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Affiliation(s)
| | - Krishan R. Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | | | - Christopher J. Anker
- Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Elliot Grodstein
- Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | - Salma K. Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Rachit Kumar
- Department of Radiation Oncology, Banner MD Anderson Cancer Center, Phoenix, AZ
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | | | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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Liu QQ, Shi XD, Ye YF, Tang QB, Lin HM, Yu XH, Zhang R, Liu C. Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with perihilar cholangiocarcinoma at high risk of recurrence. Cancer Immunol Immunother 2023; 72:1753-1761. [PMID: 36648557 DOI: 10.1007/s00262-022-03362-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/27/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND This study aimed to assess whether postoperative adjuvant chemoimmunotherapy could lead to better clinical outcomes for high-risk patients with perihilar cholangiocarcinoma (pCCA). METHODS In the cohort study, we retrospectively reviewed patients who received surgical resection for pCCA with curative intent from January 2018 to December 2021 at the Sun Yat-sen Memorial Hospital. The patients at high risk for relapse were further analyzed. Among them, 20 patients received adjuvant chemoimmunotherapy, 28 patients received adjuvant chemotherapy, and 33 patients received surgery alone. The oncological outcomes and drug-associated adverse events were evaluated. RESULTS The 2-year overall survival (OS) rates in patients treated with adjuvant chemoimmunotherapy, adjuvant chemotherapy, and surgery alone were 80.0%, 49.4% and 22.6%, respectively. Univariable and multivariable Cox analyses showed that the treatment regimen and TNM stage were associated with adverse OS. Adjuvant chemoimmunotherapy led to an increase in OS compared with adjuvant chemotherapy [hazard ratio (HR) = 3.253; 95% confidence interval (CI) 1.072-9.870; P = 0.037] or surgery alone (HR = 7.560; 95% CI 2.508-22.785; P < 0.001). The median recurrence-free survival was 22.0 months for the adjuvant chemoimmunotherapy group, 17.0 months for the adjuvant chemotherapy group, and 13.2 months for the surgery alone group (P = 0.177); these differences were not significant. The chemoimmunotherapy group was associated with more frequent hematological side effects than the chemotherapy group, but the difference was not statistically significant. CONCLUSION Postoperative adjuvant chemoimmunotherapy for resected pCCA patients showed improved OS compared with adjuvant chemotherapy or surgery alone, and further prospectively randomized controlled trials are necessary to validate these results.
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Affiliation(s)
- Qin-Qin Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Xiang-de Shi
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Yan-Fang Ye
- Clinical Research Design Division, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China
| | - Qi-Bin Tang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Hao-Ming Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Xian-Huan Yu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Rui Zhang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
| | - Chao Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
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Ohaegbulam KC, Koethe Y, Fung A, Mayo SC, Grossberg AJ, Chen EY, Sharzehi K, Kardosh A, Farsad K, Rocha FG, Thomas CR, Nabavizadeh N. The multidisciplinary management of cholangiocarcinoma. Cancer 2023; 129:184-214. [PMID: 36382577 DOI: 10.1002/cncr.34541] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/11/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022]
Abstract
Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.
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Affiliation(s)
- Kim C Ohaegbulam
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Yilun Koethe
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Alice Fung
- Department of Diagnostic Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Skye C Mayo
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Aaron J Grossberg
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Emerson Y Chen
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Kaveh Sharzehi
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, Oregon, USA
| | - Adel Kardosh
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Khashayar Farsad
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Flavio G Rocha
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA.,Department of Radiation Oncology, Dartmouth School of Medicine, Hanover, New Hampshire, USA
| | - Nima Nabavizadeh
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
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Zhang Q, Liu Z, Liu S, Wang M, Li X, Xun J, Wang X, Yang Q, Wang X, Zhang D. A novel nomogram for adult primary perihilar cholangiocarcinoma and considerations concerning lymph node dissection. Front Surg 2023; 9:965401. [PMID: 36684342 PMCID: PMC9852046 DOI: 10.3389/fsurg.2022.965401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 11/03/2022] [Indexed: 01/07/2023] Open
Abstract
Objective To construct a reliable nomogram available online to predict the postoperative survival of patients with perihilar cholangiocarcinoma. Methods Data from 1808 patients diagnosed with perihilar cholangiocarcinoma between 2004 and 2015 were extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into training and validation sets. The nomogram was established by machine learning and Cox model. The discriminant ability and prediction accuracy of the nomogram were evaluated by concordance index (C-index), receiver operator characteristic (ROC) curve and calibration curve. Kaplan-Meier curves show the prognostic value of the associated risk factors and classification system. Results Machine learning and multivariate Cox risk regression model showed that sex, age, tumor differentiation, primary tumor stage(T), lymph node metastasis(N), TNM stage, surgery, radiation, chemotherapy, lymph node dissection were associated with the prognosis of perihilar cholangiocarcinoma patients relevant factors (P < 0.05). A novel nomogram was established. The calibration plots, C-index and ROC curve for predictions of the 1-, 3-, and 5-year OS were in excellent agreement. In patients with stage T1 and N0 perihilar cholangiocarcinoma, the prognosis of ≥4 lymph nodes dissected was better than that of 1- 3 lymph nodes dissected (P < 0.01). Conclusion The nomogram prognostic prediction model can provide a reference for evaluating the prognosis and survival rate of patients with perihilar cholangiocarcinoma. Patients with stage T1 and N0 perihilar cholangiocarcinoma have more benefits by increasing the number of lymph node dissection.
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Affiliation(s)
- Qi Zhang
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
- Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, China
| | - Zehan Liu
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
- Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Shuangqing Liu
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
| | - Ming Wang
- Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Xinye Li
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Xun
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
- Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, China
| | - Xiangyu Wang
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
| | - Qin Yang
- Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, China
| | - Ximo Wang
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
| | - Dapeng Zhang
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
- Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, China
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Khuntikeo N, Pugkhem A, Srisuk T, Luvira V, Titapun A, Tipwaratorn T, Thanasukarn V, Klungboonkrong V, Wongwiwatchai J. Surgery. Recent Results Cancer Res 2023; 219:147-222. [PMID: 37660334 DOI: 10.1007/978-3-031-35166-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
This chapter provides a comprehensive background from basic to applied knowledge of surgical anatomy which is necessary for the surgical treatment of cholangiocarcinoma (CCA) patients. Significant advances that have been made in the surgical treatment of CCA were examined. For instance, in-depth details are provided for appropriate preoperative assessment and treatment to optimize patient status and to improve the outcome of surgical treatment(s). Comprehensive details are provided for the surgical techniques and outcomes of treatments for each type of CCA with clear illustrations and images. This chapter also describes the role of minimally invasive surgery and liver transplantation in CCA treatment.
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Affiliation(s)
- Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.
| | - Ake Pugkhem
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Tharatip Srisuk
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Attapol Titapun
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Theerawee Tipwaratorn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vasin Thanasukarn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vivian Klungboonkrong
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Jitraporn Wongwiwatchai
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
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Yilmaz S, Carr BI, Akbulut S. Can the Limits of Liver Transplantation Be Expanded in Perihilar Cholangiocarcinoma? J Gastrointest Cancer 2022; 53:1104-1112. [PMID: 34738188 DOI: 10.1007/s12029-021-00735-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2021] [Indexed: 02/07/2023]
Abstract
The most common location of cholangiocarcinomas is the perihilar region with a frequency of 50-70%. Current standard treatment for perihilar cholangiocarcinomas (pCCA) is surgical resection. In cases where resection treatment is possible, the 5-year survival rate is 8-40%. However, using a very strict patient selection, neoadjuvant radiochemotherapy (NRCT), staging laparotomy, and liver transplantation (LT), called "the Mayo protocol," 5-year survivals of up to 70% in pCCA were reported. This treatment protocol clearly requires an intensive workforce and a harmonious multidisciplinary approach. Reoperation and retransplantation rates are high, which is a reflection of the NRCT. Multicenter studies, systemic reviews, and meta-analysis results, comparing both resection and LT in pCCA treatment and evaluating only LT results, pointed to LT with strict patient selection and full compliance with the treatment. The results of centers experienced in LT are better in treating pCCA. According to Mayo clinical data, histopathological diagnosis could not be obtained in half of the patients with pCCA before NRCT was given. This situation can be explained by the necrosis of the tumor due to the effect of NRCT and the fact that the tumor cannot be detected in the explant liver. This situation raises the following questions: did all patients actually have pCCA? Were these good results due to some patients not having pCCA? The 5-year survival rate was worse in patients with a pathological diagnosis than those without a pathological diagnosis. However, interestingly, recurrence rates were statistically similar in both groups. There was no difference in survival between LT and resection in the R0N0 subgroup in de novo pCCA. There are still many issues that need to be addressed and corrected in pCCA, which is one of the most problematic indications for LT. Significant success has been achieved with NRCT, staging laparotomy, and LT in selected patients with pCCA developing on the basis of PSC or early-stage unresectable de novo pCCA. It can be expected that new NRCT modalities will provide better survival by expanding the indications for LT in pCCA.
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Affiliation(s)
- Sezai Yilmaz
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Brian I Carr
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Sami Akbulut
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey.
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Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study. Ann Surg 2022; 276:846-853. [PMID: 35894433 PMCID: PMC9983747 DOI: 10.1097/sla.0000000000005641] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.
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Lai Q, Lerut J. A Western World Perspective of Survival Benefit of Living Donor Liver Transplantation: A Commentary to the Article by Jackson et al. Published in JAMA Surgery. Transpl Int 2022; 35:10931. [PMID: 36388426 PMCID: PMC9640363 DOI: 10.3389/ti.2022.10931] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 10/13/2022] [Indexed: 08/29/2023]
Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, AOU Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Jan Lerut
- Institut de Recherche Clinique et Expérimentale (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium
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Rebelo A, Friedrichs J, Grilli M, Wahbeh N, Partsakhashvili J, Ukkat J, Klose J, Ronellenfitsch U, Kleeff J. Systematic review and meta-analysis of surgery for hilar cholangiocarcinoma with arterial resection. HPB (Oxford) 2022; 24:1600-1614. [PMID: 35490097 DOI: 10.1016/j.hpb.2022.04.002] [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: 12/19/2021] [Revised: 03/25/2022] [Accepted: 04/07/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND With the advances in multimodality treatment, an analysis of the outcome of arterial resections (AR) in surgery of cholangiocarcinoma is lacking. The aim of this meta-analysis was to summarize the currently available evidence onof AR for the treatment of cholangiocarcinoma. METHODS A systematic literature search was carried out according to PRISMA guidelines. RESULTS 10 retrospective cohort studies published from 2007 to 2020 with 2530 patients (408 AR group and 2122 control group) were identified. Higher in-hospital mortality rates (6.8% vs 3.3%, OR 2.65, 95% CI [1.27; 5.32], p = 0.009), higher morbidity rates (Clavien-Dindo classification ≥3 ) (52% vs 47%, OR 1.44, 95% CI [1.02; 1.75], p = 0.04) and lower 1-year, 3-year and 5-year survival rates (54% vs 69%, OR 0.55, 95% CI [0.34; 0.91 p = 0.02), (34% vs 38%, OR 0.74, 95% CI [0.55; 0.98, p = 0.03), (18% vs 29%, OR 0.54, 95% CI [0.39; 0.75, p = 0.0002) were observed in the AR group when compared to the control group. CONCLUSION Evidence from non-randomized studies shows a higher morbidity and mortality and shorter long-term survival in patients undergoing AR. However, the results are prone to selection bias, and only randomized trials comparing AR and palliative treatments AR might reveal a possible benefit of AR. SYSTEMATIC REVIEW REGISTRATION PROSPERO ID 223396.
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Affiliation(s)
- Artur Rebelo
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany.
| | - Juliane Friedrichs
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Maurizio Grilli
- Professional Information Biomedicine and Health Profession, Karlsruhe, Germany
| | - Nour Wahbeh
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Jumber Partsakhashvili
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Jörg Ukkat
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Johannes Klose
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Ulrich Ronellenfitsch
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
| | - Jörg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther-University, Halle-Wittenberg, Germany
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Elvevi A, Laffusa A, Scaravaglio M, Rossi RE, Longarini R, Stagno AM, Cristoferi L, Ciaccio A, Cortinovis DL, Invernizzi P, Massironi S. Clinical treatment of cholangiocarcinoma: an updated comprehensive review. Ann Hepatol 2022; 27:100737. [PMID: 35809836 DOI: 10.1016/j.aohep.2022.100737] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 06/25/2022] [Indexed: 02/04/2023]
Abstract
Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA). The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor. In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies.
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Affiliation(s)
- Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Alice Laffusa
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Miki Scaravaglio
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Raffaella Longarini
- Division of Oncology, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Anna Maria Stagno
- Division of Oncology, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Laura Cristoferi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Antonio Ciaccio
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Diego Luigi Cortinovis
- Division of Oncology, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 132] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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Eguchi S, Hidaka M, Hara T, Matsushima H, Soyama A. Liver transplantation for intrahepatic and hilar cholangiocellular carcinoma: Most recent updates in the literature. Ann Gastroenterol Surg 2022; 6:616-622. [PMID: 36091305 PMCID: PMC9444854 DOI: 10.1002/ags3.12567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 11/24/2022] Open
Abstract
Liver transplantation (LT) for non-hepatocellular carcinoma is still a debatable indication. Recently, hilar cholangiocellular carcinoma (hCCC) has attracted interest as a new indication for LT, but LT in this case should be carefully considered. Based on the recent meta-analysis for intrahepatic CCC (IHCCC) and our results from incidental IHCCC transplanted for other diseases such as primary sclerosing cholangitis, the indication for LT for IHCCC should be limited to a single tumor less than 2 cm. For hCCC, with pre-transplant chemoradiotherapy and careful selection criteria, long-term survival after LT could be attained. In order to improve the results of LT for intrahepatic and hCCC, further studies are required on the ingenuity of immunosuppressive therapy combined with chemotherapy, and optimal treatment methods to prevent recurrence, as well as initial case selection.
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Affiliation(s)
- Susumu Eguchi
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Masaaki Hidaka
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Takanobu Hara
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Hajime Matsushima
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
| | - Akihiko Soyama
- Department of SurgeryNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
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She WH, Dai WC, Fung JY, Cheung TT, Chan AC, Lo CM. Recurrent pyogenic cholangitis: An indication for liver transplantation. Hepatobiliary Pancreat Dis Int 2022; 21:396-398. [PMID: 34657803 DOI: 10.1016/j.hbpd.2021.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 09/03/2021] [Indexed: 02/05/2023]
Affiliation(s)
- Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - James Yy Fung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Albert Cy Chan
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China.
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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Miyagi S, Fujio A, Nakagawa K, Tokodai K, Kashiwadate T, Miyazawa K, Sasaki K, Matsumura M, Nishimaki H, Hibi T, Kamei T, Unno M. A New Strategy of Liver Transplantation for Locally Advanced Unresectable Perihilar Cholangiocarcinoma Using Living Grafts With Simultaneous Resection of Recipients' Hepatic Artery and Portal Vein Without Neoadjuvant Radiation: A Case Report. Transplant Proc 2022; 54:1643-1647. [PMID: 35810018 DOI: 10.1016/j.transproceed.2022.03.054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/13/2022] [Accepted: 03/14/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Perihilar cholangiocarcinoma (pCCA) is often unresectable, because it includes crucial blood vessels in portal area. The prognosis of locally advanced unresectable cholangiocarcinomas is extremely poor. Recently, there have been several reports of the prognosis improving drastically with transplantation and combined chemoradiation therapy. However, liver transplantation for pCCA has 2 big problems. The first is that pCCA is located at a lethal position and its progress is sometimes rapid; therefore, the optimal timing of transplantation is sometimes lost. The second is vascular complications associated with neoadjuvant radiation, especially in living donor liver transplantation (LDLT). To overcome these problems, we performed conversion surgery using LDLT with simultaneous resection of the hepatic artery and portal vein, instead of neoadjuvant radiation. Herein, we report our experience of interposition reconstruction. METHODS A 31-year-old man with primary sclerosing cholangitis (PSC) was diagnosed with locally advanced unresectable pCCA. The patient underwent radical chemotherapy (gemcitabine/cisplatin/S-1) and avoided radiation because of PSC. After 6 months, positron emission tomography-computed tomography revealed no lymph node metastasis. There was no time to wait. We immediately performed LDLT with simultaneous resection of hepatic artery and portal vein, and microsurgical reconstruction using auto-vessel grafts. RESULTS The recipient recovered and was discharged 31 days posttransplant. His liver function improved, and he has had no recurrence after LDLT. CONCLUSION LDLT with neoadjuvant radiation is associated with high risk of vascular complications. In some cases, conversion surgery after radical chemotherapy using good timing LDLT without radiation may increase chances of transplantation for locally advanced pCCA.
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Affiliation(s)
- Shigehito Miyagi
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan.
| | - Atsushi Fujio
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Kei Nakagawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Kazuaki Tokodai
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Toshiaki Kashiwadate
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Koji Miyazawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Kengo Sasaki
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Muneyuki Matsumura
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Hiroyasu Nishimaki
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University School of Medicine, Honjo, Kumamoto, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Seiryo, Sendai, Japan
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