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1
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Wu S, Wang M, Zhou Q, Tang H, Wang Z. The Expression and Clinicopathological Significance of BRAF V600E and Mucin 6 in Intrahepatic Cholangiocarcinoma: A Retrospective Study. Int J Surg Pathol 2025; 33:399-407. [PMID: 39246028 DOI: 10.1177/10668969241266930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
Aim. The study aims to explore the expression levels and clinicopathological significance of BRAF V600E and mucin 6 in intrahepatic cholangiocarcinoma. Method. Immunohistochemistry for BRAF V600E and mucin 6 was performed in 110 patients with intrahepatic cholangiocarcinoma. Subsequently, a comprehensive review of medical records and clinicopathological analysis was undertaken. Results. BRAF V600E expression was detected in 11 patients (10%); mucin 6 expression was observed in 19 intrahepatic cholangiocarcinoma specimens (17%). Thereafter, Cox regression models indicated that positive expression of either MUC6 positive (hazard ratio = 0.091, 95% confidence interval = 0.034-0.247, P < .001) and BRAF V600E positive (hazard ratio =0.150, 95% confidence interval = 0.058-0.388, P < .001) was significantly linked with longer overall survival for intrahepatic cholangiocarcinoma patients. Conclusion. The study concludes that positive expression of BRAF V600E and mucin 6 could potentially implied significant survival benefits for patients diagnosed with intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Shurui Wu
- Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China
| | - Meihong Wang
- Department of Pathology, The Hospital of PLA 80th Group Army, Shandong, China
| | - Qinghai Zhou
- Department of Hepatobiliary Surgery, Qianjiang River Hospital for Nationalities, Chongqing, China
| | - Haowen Tang
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Zhanbo Wang
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
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2
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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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Colangelo M, Di Martino M, Polidoro MA, Forti L, Tober N, Gennari A, Pagano N, Donadon M. Management of intrahepatic cholangiocarcinoma: a review for clinicians. Gastroenterol Rep (Oxf) 2025; 13:goaf005. [PMID: 39867595 PMCID: PMC11769681 DOI: 10.1093/gastro/goaf005] [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: 08/30/2024] [Revised: 11/12/2024] [Accepted: 12/18/2024] [Indexed: 01/28/2025] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy that arises from second-order biliary epithelial cells. Its incidence is gradually increasing worldwide. Well-known risk factors have been described, although in many cases, they are not identifiable. Treatment options are continuously expanding, but the prognosis of iCCA remains dismal. R0 liver resection remains the only curative treatment, but only a limited number of patients can benefit from it. Frequently, major hepatectomies are needed to completely remove the tumour. This could contraindicate surgery or increase postoperative morbidity in patients with chronic liver disease and small remnant liver volume. In cases of anticipated inadequate future liver remnant, regenerative techniques may be used to expand resectability. The role and extent of lymphadenectomy in iCCA are still matters of debate. Improvements in iCCA diagnosis and better understanding of genetic profiles might lead to optimized surgical approaches and drug therapies. The role of neoadjuvant and adjuvant therapies is broadening, gaining more and more acceptance in clinical practice. Combining surgery with locoregional therapies and novel drugs, such as checkpoint-inhibitors and molecular-targeted molecules, might improve treatment options and survival rates. Liver transplantation, after very poor initial results, is now receiving attention for the treatment of patients with unresectable very early iCCA (i.e. <2 cm) in cirrhotic livers, showing survival outcomes comparable to those of hepatocellular carcinoma. Ongoing prospective protocols are testing the efficacy of liver transplantation for patients with unresectable, advanced tumours confined to the liver, with sustained response to neoadjuvant treatment. In such a continuously changing landscape, the aim of our work is to review the state-of-the-art in the surgical and medical treatment of iCCA.
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Affiliation(s)
- Matteo Colangelo
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Marcello Di Martino
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Laura Forti
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
| | - Nastassja Tober
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
| | - Alessandra Gennari
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Nico Pagano
- Division of Gastroenterology, University Maggiore Hospital della Carità, Novara, Italy
| | - Matteo Donadon
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
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4
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Harrison JM, Visser BC. Cholangiocarcinoma. Surg Clin North Am 2024; 104:1281-1293. [PMID: 39448128 DOI: 10.1016/j.suc.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Management of intrahepatic cholangiocarcinoma relies on a thorough understanding of the tumor's location and proximity to critical vasculobiliary structures. Mid-common bile duct tumors may require hemihepatectomy or pancreatoduodenectomy based on the status of the intraoperative frozen section. Distal common bile tumors are treated with pancreatoduodenectomy. When appropriate, volumetric assessment of the remnant liver should be performed to identify cases requiring preoperative liver augmentation strategies. A similar strategy should be employed for perihilar tumors, which require a right trisegmentectomy with bilioenteric reconstruction to achieve a negative margin. Adjuvant systemic therapy is recommended and increasing usage of neoadjuvant treatment is being incorporated into borderline resectable or regionally advanced cases.
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Affiliation(s)
- Jon M Harrison
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA
| | - Brendan C Visser
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA.
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5
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Patel S, Hasanain A, Fang A, Khavandi MM, Mathias T, Cohen EI, Etezadi V, Sabri SS, Camacho JC, Yarmohammadi H, Banovac F, He AR, Radkani P, Habibollahi P, Nezami N. Intra-arterial locoregional therapies for intrahepatic cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2024; 18:505-519. [PMID: 39246149 DOI: 10.1080/17474124.2024.2402358] [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: 01/21/2024] [Revised: 09/02/2024] [Accepted: 09/05/2024] [Indexed: 09/10/2024]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) is the 2nd most common primary liver malignancy. For nonsurgical candidates, the primary treatment option is systemic chemotherapy, which can be combined with locoregional therapies to enhance local control. Common intra-arterial locoregional therapies include transarterial hepatic embolization, conventional transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, transarterial radioembolization with Yttrium-90 microspheres, and hepatic artery infusion. This article aims to review the latest literature on intra-arterial locoregional therapies for treating ICC. AREAS COVERED A literature search was conducted on PubMed using keywords: intrahepatic cholangiocarcinoma, intra-arterial locoregional therapy, embolization, chemoembolization, radioembolization, hepatic artery infusion, and immunotherapy. Articles from 2008 to 2024 were reviewed. Survival data from retrospective and prospective studies, meta-analyses, and clinical trials were evaluated. EXPERT OPINION Although no level I evidence supports the superiority of any specific intra-arterial therapy, there has been a shift toward favoring radioembolization. In our expert opinion, radioembolization may offer superior outcomes when performed by skilled operators with meticulous planning and personalized dosimetry, particularly for radiation segmentectomy or treating lobar/bilobar disease in appropriate candidates.
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Affiliation(s)
- Sandhya Patel
- Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Alina Hasanain
- Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Adam Fang
- Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Mohammad Mahdi Khavandi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Trevor Mathias
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Emil I Cohen
- Division of Vascular and Interventional Radiology, Department of Radiology, The Georgetown University Medical Center, Washington, DC, USA
| | - Vahid Etezadi
- Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Saher S Sabri
- Division of Vascular and Interventional Radiology, Department of Radiology, The Georgetown University Medical Center, Washington, DC, USA
| | - Juan C Camacho
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL, USA
| | - Hooman Yarmohammadi
- Division of Interventional Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Filip Banovac
- Division of Vascular and Interventional Radiology, Department of Radiology, The Georgetown University Medical Center, Washington, DC, USA
| | - Aiwu R He
- Department of Medicine, The Georgetown University School of Medicine, Washington, DC, USA
| | - Pejman Radkani
- Department of Surgery, The Georgetown University School of Medicine, Washington, DC, USA
| | - Peiman Habibollahi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Radiology, The Georgetown University Medical Center, Washington, DC, USA
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Esmail A, Badheeb M, Alnahar BW, Almiqlash B, Sakr Y, Al-Najjar E, Awas A, Alsayed M, Khasawneh B, Alkhulaifawi M, Alsaleh A, Abudayyeh A, Rayyan Y, Abdelrahim M. The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma. Pharmaceuticals (Basel) 2024; 17:910. [PMID: 39065760 PMCID: PMC11279608 DOI: 10.3390/ph17070910] [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: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06610, USA
| | | | - 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
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ali Awas
- Faculty of Medicine and Health Sciences, University of Science and Technology, Sanaa P.O. Box 15201-13064, Yemen
| | | | - Bayan Khasawneh
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | | | - Amneh Alsaleh
- Department of Medicine, Desert Regional Medical Center, Palm Springs, CA 92262, USA
| | - 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, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
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7
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Woodhead G, Lee S, Struycken L, Goldberg D, Hannallah J, Young S. Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma. Life (Basel) 2024; 14:217. [PMID: 38398726 PMCID: PMC10890186 DOI: 10.3390/life14020217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/22/2023] [Accepted: 01/12/2024] [Indexed: 02/25/2024] Open
Abstract
Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.
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Affiliation(s)
- Gregory Woodhead
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Sean Lee
- Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine, Middletown, NY 10027, USA;
| | - Lucas Struycken
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Daniel Goldberg
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Jack Hannallah
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Shamar Young
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
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8
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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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9
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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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Ning Z, Xie L, Yan X, Hua Y, Shi W, Lin J, Xu L, Meng Z. Transarterial chemoembolization plus lenvatinib with or without a PD-1 inhibitor for advanced and metastatic intrahepatic cholangiocarcinoma: a retrospective real-world study. Br J Radiol 2023; 96:20230079. [PMID: 37660471 PMCID: PMC10546439 DOI: 10.1259/bjr.20230079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 07/08/2023] [Accepted: 07/25/2023] [Indexed: 09/05/2023] Open
Abstract
OBJECTIVES Most patients with intrahepatic cholangiocarcinoma (ICC) present with locally advanced or metastatic disease. We report the combined potency of transarterial chemoembolization (TACE), lenvatinib and programmed cell death-1 (PD-1) inhibitors in patients with advanced and metastatic ICC. METHODS This retrospective study enrolled 32 patients with advanced or metastatic ICC between January 2017 and August 2021. Eligible patients had received gemcitabine-based TACE combined with lenvatinib with or without PD-1 inhibitor in any line of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Risk factors associated with OS were assessed using univariate and multivariate Cox regression analyses. RESULTS Eighteen patients received a combination of TACE and lenvatinib (TL group) and 14 patients received TACE and lenvatinib plus aPD-1 inhibitor (TLP group). The median follow-up time was 19.8 months (range 1.8-37.8). The median OS was 25.3 months (95% CI 18.5-32.1) and the median PFS was 7.3 months (95% CI 4.9-9.7). Partial response was achieved in 10 patients (31.3%), and stable disease in 13 (40.6 %) with disease control rate of 71.9%. The median OS was comparable in the TL and TLP groups (22.4 vs 27.3 months, respectively; hazard ratio: 1.245, 95% CI 0.4245-3.653; p = 0.687). The regression analysis revealed that, regardless of treatment group, a favorable independent prognostic factor for OS was HBV/HCV infection (HR: 0.063, 95% CI 0.009-0.463; p = 0.007). There were no treatment-related deaths and 81.3% of study participants experienced adverse events (AEs), the majority of which were of moderate severity (71.8% Grade 1-2). CONCLUSIONS Gemcitabine-based TACE plus lenvatinib with or without aPD-1 inhibitor was well tolerated and provided promising therapeutic outcomes for patients with advanced and metastatic ICC. ADVANCES IN KNOWLEDGE Monotherapy with TACE, or Lenvatinib, or PD-1 inhibitors has shown limited efficacy over standard first-line chemotherapy in advanced and metastatic ICC. This work suggested the combined potency of these treatments and well-tolerance.
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Bourien H, Pircher CC, Guiu B, Lamarca A, Valle JW, Niger M, Edeline J. Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient? Cancers (Basel) 2023; 15:4217. [PMID: 37686493 PMCID: PMC10486617 DOI: 10.3390/cancers15174217] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/08/2023] [Accepted: 08/14/2023] [Indexed: 09/10/2023] Open
Abstract
For unresectable intrahepatic cholangiocarcinoma (iCC), different locoregional treatments (LRT) could be proposed to patients, including radiofrequency ablation (RFA) and microwave ablation (MWA), external beam radiotherapy (EBRT) or transarterial treatments, depending on patient and tumor characteristics and local expertise. These different techniques of LRT have not been compared in a randomized clinical trial; most of the relevant studies are retrospective and not comparative. The aim of this narrative review is to help clinicians in their everyday practice discuss the pros and cons of each LRT, depending on the individual characteristics of their patients.
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Affiliation(s)
- Héloïse Bourien
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
| | - Chiara Carlotta Pircher
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Boris Guiu
- Interventional Radiology Department, CHU de Montpellier, 34090 Montpellier, France;
| | - Angela Lamarca
- Oncology Department, Fundación Jiménez Díaz University Hospital, 28022 Madrid, Spain;
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Juan W Valle
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Monica Niger
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Julien Edeline
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
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12
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Auer TA, Collettini F, Segger L, Pelzer U, Mohr R, Krenzien F, Gebauer B, Geisel D, Hosse C, Schöning W, Fehrenbach U. Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma. Cancers (Basel) 2023; 15:cancers15092655. [PMID: 37174120 PMCID: PMC10177209 DOI: 10.3390/cancers15092655] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 05/01/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023] Open
Abstract
cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future.
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Affiliation(s)
- Timo Alexander Auer
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
| | - Federico Collettini
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
| | - Laura Segger
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Felix Krenzien
- Department of Surgery-CVK/CCM, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Bernhard Gebauer
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Dominik Geisel
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Clarissa Hosse
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery-CVK/CCM, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
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13
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Morawitz J, Bruckmann NM, Jannusch K, Kirchner J, Antoch G, Loosen S, Luedde T, Roderburg C, Minko P. Update on Locoregional Therapies for Cholangiocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082368. [PMID: 37190295 DOI: 10.3390/cancers15082368] [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: 04/06/2023] [Accepted: 04/17/2023] [Indexed: 05/17/2023] Open
Abstract
Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies.
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Affiliation(s)
- Janna Morawitz
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
| | - Nils-Martin Bruckmann
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
| | - Kai Jannusch
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
| | - Julian Kirchner
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
| | - Gerald Antoch
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
| | - Sven Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine, University Düsseldorf, D-40225 Düsseldorf, Germany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine, University Düsseldorf, D-40225 Düsseldorf, Germany
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine, University Düsseldorf, D-40225 Düsseldorf, Germany
| | - Peter Minko
- Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, D-40225 Düsseldorf, Germany
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14
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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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15
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Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023; 73:198-222. [PMID: 36260350 DOI: 10.3322/caac.21759] [Citation(s) in RCA: 201] [Impact Index Per Article: 100.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/25/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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16
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Dewald CLA, Becker LS, Meine TC, Maschke SK, Wacker FK, Saborowski A, Vogel A, Hinrichs JB. New perspectives in unresectable cholangiocarcinoma? Evaluation of chemosaturation with percutaneous hepatic perfusion as a palliative treatment option. Clin Exp Metastasis 2023; 40:95-104. [PMID: 36417096 PMCID: PMC9898387 DOI: 10.1007/s10585-022-10193-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 10/31/2022] [Indexed: 11/24/2022]
Abstract
Cholangiocarcinoma (CCA) are the second most common primary liver tumors and carry a dismal prognosis. Chemosaturation with percutaneous hepatic perfusion (PHP) is a palliative, intra-arterial therapeutic approach that provides a high dose chemotherapy of the liver with reduced systemic exposure. Aim of this retrospective, monocentric study was to analyze PHP as a palliative treatment for unresectable CCA. Toxicity, adverse events and complications were classified using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic mPFS (mhPFS) were computed using Kaplan-Meier estimation. In total 17 patients were treated with 42 PHP between 10/2014 and 09/2020. No significant complications occurred during the interventions. mOS was 27.6 (interquartile range (IQR) 16.5-37) months from first diagnosis and 9.9 (IQR 3.8-21) months from first PHP. mPFS was 4 (IQR 2-7) and mhPFS was 4 (IQR 3-10) months. ORR was 25% and DCR 75%. Significant, but transient hematotoxicity was frequent with grade 3/4 thrombopenia after 50%, leukopenia after 26% and anaemia after 21% of the interventions. An increase of transaminases (AST increase after 21% and ALT increase after 14% of the PHP) developed more often than a deterioration of the liver synthesis capacity. Salvage treatment with PHP has the potential to prolong life in selected patients with unresectable, refractory cholangiocarcinoma. The interventional procedure is safe. Post-interventional toxicity is frequent but manageable.
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Affiliation(s)
- Cornelia L A Dewald
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
| | - Lena S Becker
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Timo C Meine
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Sabine K Maschke
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Frank K Wacker
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Jan B Hinrichs
- Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
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17
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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18
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He M, Jiang N, Yin X, Xu A, Mu K. Conventional and drug-eluting beads transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a systematic review and pooled analysis. J Cancer Res Clin Oncol 2023; 149:531-540. [PMID: 36402872 DOI: 10.1007/s00432-022-04485-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 11/14/2022] [Indexed: 11/21/2022]
Abstract
PURPOSE Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have poor survival. Conventional transarterial chemoembolization (c-TACE) and drug-eluting beads transarterial chemoembolization (DEB-TACE) are two treatment options for ICC, and this systematic review describes the efficacy of each of these modalities for unresectable ICC to guide clinical practice. METHODS A literature search was performed in PubMed, Web of Science, and Embase databases regarding transhepatic arterial chemoembolization for intrahepatic cholangiocarcinoma. The Newcastle-Ottawa quality assessment Scale (NOS) was used to assess the risk of bias. Tumor response, disease control, and 1-, 2-, 3-year overall survival rate were pooled for estimation. RESULTS The number of initial search results was 1035, and 19 articles met the inclusion criteria for this study after the screening. A total of 23 study cohorts and 1091 patients were provided. The pooled objective response rate (ORR) for c-TACE and DEB-TACE treating ICC was 29.4% (95% CI 11.6-50.8%) and 51.2% (95% CI 30.6-71.7%), respectively; disease control rate (DCR) was 72.8% (95% CI 55.6-87.3%) and 88.7% (95% CI 78.8-96.2%), respectively. The pooled survival rate at 1 year, 2 year, and 3 year was 49.7% (95% CI 39.1-60.3%), 24.0% (95% CI 12.6-37.3%), and 23.5% (95% CI 11.1-38.7%) for c-TACE; 58.6% (95% CI 44.2-72.3%), 26.7% (95% CI 18.1-36.3%), and 16.2% (95% CI 6.0-29.4%) for DEB-TACE. CONCLUSION The descriptive analysis suggested that DEB-TACE treatment for ICC may have better tumor response and disease control rates than c-TACE treatment, but the impact on overall survival was not demonstrated significantly by DEB-TACE treatment.
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Affiliation(s)
- Meiya He
- Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 40030, China
| | - Nan Jiang
- Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 40030, China
| | - Xiaoxv Yin
- Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 40030, China
| | - Anhui Xu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue 1095, Wuhan, 430030, China.
| | - Ketao Mu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue 1095, Wuhan, 430030, China.
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19
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Locoregional Approaches in Cholangiocarcinoma Treatment. Cancers (Basel) 2022; 14:cancers14235853. [PMID: 36497334 PMCID: PMC9740081 DOI: 10.3390/cancers14235853] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/20/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a rare hepatic malignant tumor with poor prognosis due to late detection and anatomic factors limiting the applicability of surgical resection. Without surgical resection, palliation is the most common approach. In non-surgical cases contained within the liver, locoregional therapies provide the best chance for increased survival and disease control. The most common methods, transarterial chemoembolization and transarterial radioembolization, target tumors by embolizing their blood supply and limiting the tumor's ability to metabolize. Other treatments induce direct damage via thermal ablation to tumor tissue to mediate their anti-tumor efficacy. Recent studies have begun to explore roles for these therapies outside their previous role of palliation. This review will outline the mechanisms of each of these treatments, along with their effects on overall survival, while comparing these to non-locoregional therapies.
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20
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Safdar NZ, Hakeem AR, Faulkes R, James F, Mason L, Masson S, Powell J, Rowe I, Shetty S, Jones R, Spiers HVM, Halliday N, Baker J, Thorburn D, Prasad R, Parker R. Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma. Transpl Int 2022; 35:10802. [PMID: 36406780 PMCID: PMC9667791 DOI: 10.3389/ti.2022.10802] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/18/2022] [Indexed: 12/03/2022]
Abstract
Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.
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Affiliation(s)
- Nawaz Z. Safdar
- School of Medicine, University of Leeds, Leeds, United Kingdom
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Abdul R. Hakeem
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | | | - Fiona James
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Lisa Mason
- Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Steven Masson
- Newcastle Upon Tyne Hospitals, Newcastle, United Kingdom
| | - James Powell
- Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Ian Rowe
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Shishir Shetty
- University Hospitals Birmingham, Birmingham, United Kingdom
| | - Rebecca Jones
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Harry V. M. Spiers
- Roy Calne Transplant Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | | | | | | | - Raj Prasad
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
| | - Richard Parker
- Leeds Liver Unit, St James’ University Hospital, Leeds, United Kingdom
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21
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Bitzer M, Voesch S, Albert J, Bartenstein P, Bechstein W, Blödt S, Brunner T, Dombrowski F, Evert M, Follmann M, La Fougère C, Freudenberger P, Geier A, Gkika E, Götz M, Hammes E, Helmberger T, Hoffmann RT, Hofmann WP, Huppert P, Kautz A, Knötgen G, Körber J, Krug D, Lammert F, Lang H, Langer T, Lenz P, Mahnken A, Meining A, Micke O, Nadalin S, Nguyen HP, Ockenga J, Oldhafer K, Paprottka P, Paradies K, Pereira P, Persigehl T, Plauth M, Plentz R, Pohl J, Riemer J, Reimer P, Ringwald J, Ritterbusch U, Roeb E, Schellhaas B, Schirmacher P, Schmid I, Schuler A, von Schweinitz D, Seehofer D, Sinn M, Stein A, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Tholen R, Vogel A, Vogl T, Vorwerk H, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wittekind C, Wörns MA, Galle P, Malek N. S3-Leitlinie – Diagnostik und Therapie biliärer Karzinome. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e186-e227. [PMID: 35148560 DOI: 10.1055/a-1589-7854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- M Bitzer
- Medizinische Klinik I, Universitätsklinikum Tübingen
| | - S Voesch
- Medizinische Klinik I, Universitätsklinikum Tübingen
| | - J Albert
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Robert-Bosch-Krankenhaus, Stuttgart
| | - P Bartenstein
- Klinik und Poliklinik für Nuklearmedizin, LMU Klinikum, München
| | - W Bechstein
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt
| | - S Blödt
- AWMF-Geschäftsstelle, Berlin
| | - T Brunner
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg
| | - F Dombrowski
- Institut für Pathologie, Universitätsmedizin Greifswald
| | - M Evert
- Institut für Pathologie, Regensburg
| | - M Follmann
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V., Berlin
| | - C La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Tübingen
| | | | - A Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - E Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | | | - E Hammes
- Lebertransplantierte Deutschland e. V., Ansbach
| | - T Helmberger
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | - R T Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Dresden
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | - P Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühl
| | - A Kautz
- Deutsche Leberhilfe e.V., Köln
| | - G Knötgen
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - J Körber
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, Bad Kreuznach
| | - D Krug
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - H Lang
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
| | - T Langer
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V., Berlin
| | - P Lenz
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - A Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - A Meining
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg
| | - O Micke
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld
| | - S Nadalin
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen
| | | | - J Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen
| | - K Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg
| | - P Paprottka
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München
| | - K Paradies
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - P Pereira
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München
| | - T Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | | | - R Plentz
- Klinikum Bremen-Nord, Innere Medizin, Bremen
| | - J Pohl
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - J Riemer
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - P Reimer
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - J Ringwald
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen
| | | | - E Roeb
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - B Schellhaas
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - P Schirmacher
- Pathologisches Institut, Universitätsklinikum Heidelberg
| | - I Schmid
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München
| | - A Schuler
- Medizinische Klinik, Alb Fils Kliniken GmbH, Göppingen
| | | | - D Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - M Sinn
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf
| | - A Stein
- Hämatologisch-Onkologischen Praxis Eppendorf, Hamburg
| | - A Stengel
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen
| | | | - C Stoll
- Klinik Herzoghöhe Bayreuth, Bayreuth
| | - A Tannapfel
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - A Taubert
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - J Trojan
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - R Tholen
- Deutscher Verband für Physiotherapie e. V., Köln
| | - A Vogel
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - T Vogl
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - H Vorwerk
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - F Wacker
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - O Waidmann
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - H Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - H Wege
- Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - D Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | - C Wittekind
- Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig
| | - M A Wörns
- Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - P Galle
- Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - N Malek
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
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22
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Voesch S, Bitzer M, Malek N. [Clinical relevance of the new S3 guideline on hepatocellular carcinoma and biliary tract cancer for practitioners]. Radiologe 2022; 62:200-204. [PMID: 35147708 DOI: 10.1007/s00117-022-00970-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2022] [Indexed: 01/27/2023]
Abstract
The update of the S3 German guideline for the management of the hepatocellular carcinoma and biliary tract cancer contains a comprehensive revision of the guideline for hepatocellular carcinoma and establishes a new guideline for biliary tract cancer. In recent years several studies have been conducted to improve diagnostic and therapeutic options for liver cancer. Magnetic resonance imaging (MRI) and biopsy are important for the diagnosis of hepatocellular carcinoma or cholangiocarcinoma. This guideline shows the progress in the treatment options for hepatocellular carcinoma, including advances in liver transplantation, bridging and downstaging. For cholangiocarcinoma there is a focus on interventional treatment and resection. This guideline also emphasizes the need of molecular diagnostics and the resulting treatment options in targeted therapy.
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Affiliation(s)
- Sabrina Voesch
- Medizinische Klinik I, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland.
| | - M Bitzer
- Medizinische Klinik I, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland
| | - N Malek
- Medizinische Klinik I, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland
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23
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Fabritius MP, Ben Khaled N, Kunz WG, Ricke J, Seidensticker M. Image-Guided Local Treatment for Unresectable Intrahepatic Cholangiocarcinoma-Role of Interventional Radiology. J Clin Med 2021; 10:jcm10235574. [PMID: 34884275 PMCID: PMC8658286 DOI: 10.3390/jcm10235574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/24/2021] [Accepted: 11/24/2021] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Matthias P. Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany;
- German Cancer Consortium (DKTK), Partner Site Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Wolfgang G. Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
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24
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Mukund A, V Srinivasan S, Rana S, Vijayaraghavan R, Patidar Y, Arora V, Jindal A, Choudhury A, Shasthry SM, Sarin SK. Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study. Clin Radiol 2021; 77:121-129. [PMID: 34789395 DOI: 10.1016/j.crad.2021.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/14/2021] [Indexed: 11/16/2022]
Abstract
AIM To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.
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Affiliation(s)
- A Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - S V Srinivasan
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S Rana
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - R Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Y Patidar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - V Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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25
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Outcome and Safety after 103 Radioembolizations with Yttrium-90 Resin Microspheres in 73 Patients with Unresectable Intrahepatic Cholangiocarcinoma-An Evaluation of Predictors. Cancers (Basel) 2021; 13:cancers13215399. [PMID: 34771563 PMCID: PMC8582544 DOI: 10.3390/cancers13215399] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary TARE with yttrium-90 (90Y) resin microspheres is emerging in many countries as a treatment option for ICC. Identification of patients that will benefit from TARE is a clinically relevant problem with individual but also economical relevance. The aim of this study was to detect outcome predictors for patients with ICC after TARE with 90Y resin microspheres. We found TARE with 90Y resin microspheres to be a safe treatment option for unresectable ICC. Predictive factors for TARE in ICC are CA-19-9 response, tumor burden, and cholinesterase. Multiple TARE sessions might further improve overall survival. Abstract Trans-arterial radioembolization (TARE) is increasingly evaluated for unresectable intrahepatic cholangiocarcinoma (ICC). Not all ICC patients benefit equally well from TARE. Therefore, we sought to evaluate variables predicting progression-free survival (PFS) and overall survival (OS). Patients with non-resectable ICC underwent TARE and were treated with 90Y resin microspheres. Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on PFS and OS. A total of 103 treatments were administered to 73 patients without major complications or toxicity. Mean OS was 18.9 months (95% confidence intervals (CI); 13.9–23.9 months). Mean and median PFS were 10.1 months (95% CI; 7.9–12.2) and 6.4 months (95% CI; 5.20–7.61), respectively. Median OS and PFS were significantly prolonged in patients with baseline cholinesterase (CHE) ≥ 4.62 kU/L (OS: 14.0 vs. 5.5 months; PFS: 6.9 vs. 3.2 months; p < 0.001). Patients with a tumor burden ≤ 25% had a significantly longer OS (15.2 vs. 6.6 months; p = 0.036). Median PFS was significantly longer for patients with multiple TARE cycles (24.4 vs. 5.8 months; p = 0.04). TARE is a considerable and safe option for unresectable ICC. CA-19-9, CHE, and tumor burden have predictive value for survival in patients treated with TARE. Multiple TARE treatments might further improve survival; this has to be confirmed by further studies.
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26
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Ben Khaled N, Jacob S, Rössler D, Bösch F, De Toni EN, Werner J, Ricke J, Mayerle J, Seidensticker M, Schulz C, Fabritius MP. Current State of Multidisciplinary Treatment in Cholangiocarcinoma. Dig Dis 2021; 40:581-595. [PMID: 34695826 DOI: 10.1159/000520346] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 10/19/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a highly aggressive malignancy, and its incidence seems to be increasing over the last years. Given the high rate of irresectability at the time of initial diagnosis, new treatment approaches are important to achieve better patient outcomes. Our review provides an overview of current multimodal therapy options across different specialties of gastroenterology/oncology, surgery, and interventional radiology. SUMMARY CCA is subdivided into clinically and molecularly distinct phenotypes. Surgical treatment currently is the only potentially curative therapy, but unfortunately, the majority of all patients are not eligible for resection at the time of initial diagnosis due to anatomic location, inadequate hepatic reserve, metastatic disease, or limiting comorbidities. However, multimodal treatment options are available to prolong survival, relieve symptoms, and maintain life quality. KEY MESSAGES The treatment of CCA is complex and requires close interdisciplinary collaboration and individualized treatment planning to ensure optimal patient care at specialized centers. Molecular profiling of patients and inclusion into clinical trials is highly recommended.
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Affiliation(s)
- Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Sven Jacob
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Daniel Rössler
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Florian Bösch
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Enrico N De Toni
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Jens Werner
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Julia Mayerle
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
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27
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Zori AG, Yang D, Draganov PV, Cabrera R. Advances in the management of cholangiocarcinoma. World J Hepatol 2021; 13:1003-1018. [PMID: 34630871 PMCID: PMC8473501 DOI: 10.4254/wjh.v13.i9.1003] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/09/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a primary malignancy of the bile ducts with three anatomically and molecularly distinct entities: Intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA. As a result of phenotypic and anatomic differences they differ significantly with respect to management. For each type of CCA there have been significant changes in management over the last several years which will be discussed in this review. Although resection remains the standard of care for all types of CCA, liver transplantation has been established as curative treatment for selected patients with pCCA and is being evaluated for iCCA with early success. With respect to systemic therapy capecitabine is now first line adjuvant therapy for all biliary tract malignancies after curative intent resection. Progress in exploiting the pathologic mutations and molecular abnormalities has also yielded regulatory approval of targeted therapy for CCA in patients with acquired alterations in the fibroblast growth factor receptor. There is also increased consensus in managing malignant biliary obstruction associated with CCA where pre-operative biliary stenting is not beneficial while self-expanding metal stents have been shown to be superior to plastic stents in patients who are not surgical candidates.
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Affiliation(s)
- Andreas G Zori
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Dennis Yang
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Peter V Draganov
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
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28
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Nguyen MLT, Toan NL, Bozko M, Bui KC, Bozko P. Cholangiocarcinoma Therapeutics: An Update. Curr Cancer Drug Targets 2021; 21:457-475. [PMID: 33563168 DOI: 10.2174/1568009621666210204152028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/12/2020] [Accepted: 11/20/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. OBJECTIVE This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. METHODS Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. RESULTS CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. CONCLUSION This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.
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Affiliation(s)
- Mai Ly Thi Nguyen
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Maria Bozko
- Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
| | - Khac Cuong Bui
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Przemyslaw Bozko
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
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29
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Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma. Cancers (Basel) 2021; 13:cancers13153657. [PMID: 34359560 PMCID: PMC8345178 DOI: 10.3390/cancers13153657] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/06/2021] [Accepted: 07/19/2021] [Indexed: 01/17/2023] Open
Abstract
Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.
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30
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Li H, Chen L, Zhu GY, Yao X, Dong R, Guo JH. Interventional Treatment for Cholangiocarcinoma. Front Oncol 2021; 11:671327. [PMID: 34268114 PMCID: PMC8276166 DOI: 10.3389/fonc.2021.671327] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/09/2021] [Indexed: 12/11/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common type of primary liver malignancy. The latest classification includes intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with the latter one further categorized into perihilar and distal cholangiocarcinoma. Although surgical resection is the preferred treatment for CCA, less than half of the patients are actually eligible for radical surgical resection. Interventional treatment, such as intra-arterial therapies, ablation, and brachytherapy (iodine-125 seed implantation), has become an acceptable palliative treatment for patients with unresectable CCA. For these patients, interventional treatment is helpful for locoregional control, symptom relief, and improving quality of life. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research in this article.
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Affiliation(s)
- Hang Li
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Li Chen
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Guang-Yu Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Xijuan Yao
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Rui Dong
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jin-He Guo
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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The Addition of Transarterial Chemoembolization to Palliative Chemotherapy Extends Survival in Intrahepatic Cholangiocarcinoma. J Clin Med 2021; 10:jcm10122732. [PMID: 34205670 PMCID: PMC8235389 DOI: 10.3390/jcm10122732] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/15/2021] [Accepted: 06/18/2021] [Indexed: 12/29/2022] Open
Abstract
Incidence and mortality of intrahepatic cholangiocarcinoma (iCCA) have been increasing continuously. Recent studies suggest that the combination of palliative chemotherapy (pCTX) and transarterial chemoembolization (TACE) improves overall survival (OS). This study aimed to evaluate the outcome of patients treated with TACE and pCTX in unresectable iCCA at our tertiary care center. A group of 14 patients was treated with both pCTX and TACE. The non-randomized control group of 59 patients received pCTX alone. Patients received a median of two pCTX lines in both groups. Those treated with TACE underwent a median number of 3.5 sessions. Median OS from the time of unresectability was 26.2 months in the pCTX + TACE group versus 13.1 months in the pCTX group (p = 0.008). Controlling for albumin, bilirubin, ECOG (Eastern Cooperative Oncology Group) performance status, and UICC (Union for International Cancer Control) stage, the addition of TACE still conferred an OS benefit of 12.95 months (p = 0.014). A propensity score matching analysis yielded an OS benefit of 14 months from the time of unresectability for the pCTX + TACE group (p = 0.020). The addition of TACE to pCTX may provide an OS benefit for patients with unresectable iCCA. Thus, patients with liver-dominant iCCA undergoing standard-of-care pCTX should be considered for additional treatment with TACE.
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Feng F, Gao Q, Wu Y, Liu C, Yu Y, Li B, Chu K, Yi B, Cheng Q, Jiang X. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs. cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: A retrospective cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2363-2368. [PMID: 34119376 DOI: 10.1016/j.ejso.2021.05.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/20/2021] [Accepted: 05/07/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefits in patients with intraperitoneal malignant lesions, but there is no study specific to intrahepatic cholangiocarcinoma (ICC). PURPOSE To compare the prognosis of patients with advanced ICC undergoing CRS + HIPEC compared with CRS alone. METHODS This study was a retrospective cohort study of patients with advanced ICC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between 01/2014 and 12/2018. The patients were divided into either CRS + HIPEC or CRS group based on the treatment they received. Overall survival (OS), complications, hospital stay, biochemical indicators, tumor markers, and number of HIPEC were examined. RESULTS There were 51 and 61 patients in the CRS + HIPEC and CRS groups, respectively. There were no differences between the groups regarding preoperative CA19-9 levels (421 ± 381 vs. 523 ± 543 U/mL, P = 0.208). The hospital stay was longer in the CRS + HIPEC group (22.2 ± 10.0 vs. 18.6 ± 7.6 days, P = 0.033). The occurrence of overall complications was similar in the two groups (37.2% vs. 34.4%, P = 0.756). The postoperative CA19-9 levels were lower in the CRS + HIPEC group compared with the CRS group (196 ± 320 vs. 337 ± 396 U/mL, P = 0.044). The median OS was longer in the CRS + HIPEC group than in the CRS group (25.53 vs. 11.17 months, P < 0.001). Compared with the CRS group, the CRS + HIPEC group showed a higher occurrence of leukopenia (7.8% vs. 0, P = 0.040) but a lower occurrence of total bilirubin elevation (15.7% vs. 37.7%, P = 0.032). CONCLUSION CRS + HIPEC could be a treatment option for patients with advanced ICC, with improved OS and similar complications and adverse events compared with CRS alone.
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Affiliation(s)
- Feiling Feng
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Qingxiang Gao
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Yue Wu
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Chen Liu
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Yong Yu
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Bin Li
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Kaijian Chu
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Bin Yi
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China
| | - Qingbao Cheng
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China.
| | - Xiaoqing Jiang
- Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, PR China.
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Cai Z, He C, Zhao C, Lin X. Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:611118. [PMID: 33868997 PMCID: PMC8047640 DOI: 10.3389/fonc.2021.611118] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 03/18/2021] [Indexed: 12/30/2022] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. Methods Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. Results ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. Conclusions HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.
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Affiliation(s)
- Zhiyuan Cai
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chongyu Zhao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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Mosconi C, Solaini L, Vara G, Brandi N, Cappelli A, Modestino F, Cucchetti A, Golfieri R. Transarterial Chemoembolization and Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma-a Systemic Review and Meta-Analysis. Cardiovasc Intervent Radiol 2021; 44:728-738. [PMID: 33709272 DOI: 10.1007/s00270-021-02800-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/05/2021] [Indexed: 01/07/2023]
Abstract
PURPOSE Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. MATERIALS AND METHODS A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. RESULTS A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4-16.1). The survival difference was small (d = 0.112) at 1 year and negligible at 2 years (d = 0.028) and at 3 years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). CONCLUSION In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).
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Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy.
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy.,Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Giulio Vara
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Nicolò Brandi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy.,Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy.,Department of Specialized, Diagnostic and Experimental Medicine - DIMES, Alma Mater Studiorum - University of Bologna, Bologna, Italy
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35
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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Abstract
Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.
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Affiliation(s)
- Pouya Entezari
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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37
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Italian Clinical Practice Guidelines on Cholangiocarcinoma - Part II: Treatment. Dig Liver Dis 2020; 52:1430-1442. [PMID: 32952071 DOI: 10.1016/j.dld.2020.08.030] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/17/2020] [Accepted: 08/17/2020] [Indexed: 01/27/2023]
Abstract
Currently, the only curative treatment for cholangiocarcinoma (CCA) is surgical resection, though this treatment is possible in less than 40% of patients. However, recent improvements in preoperative management have led to a higher number of patients who are candidates for this procedure. For unresectable patients, progress is ongoing in terms of locoregional and chemoradiation treatments and target therapies, especially in the definition of patient selection criteria. This is the second part of the Italian CCA guidelines, dealing with CCA treatment, that have been formulated in accordance with Italian National Institute of Health indications and developed according to the GRADE method and related advancements.
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38
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Akateh C, Ejaz AM, Pawlik TM, Cloyd JM. Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma. World J Hepatol 2020; 12:693-708. [PMID: 33200010 PMCID: PMC7643214 DOI: 10.4254/wjh.v12.i10.693] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/21/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Aslam M Ejaz
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Timothy Michael Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
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Savic LJ, Chapiro J, Funai E, Bousabarah K, Schobert IT, Isufi E, Geschwind JFH, Stark S, He P, Rudek MA, Perez Lozada JC, Ayyagari R, Pollak J, Schlachter T. Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies. Eur Radiol 2020; 31:3002-3014. [PMID: 33063185 DOI: 10.1007/s00330-020-07380-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/19/2020] [Accepted: 10/06/2020] [Indexed: 01/24/2023]
Abstract
OBJECTIVES To evaluate the prognostic potential of Lipiodol distribution for the pharmacokinetic (PK) profiles of doxorubicin (DOX) and doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE). METHODS This prospective clinical trial ( ClinicalTrials.gov : NCT02753881) included 30 consecutive participants with liver malignancies treated with cTACE (5/2016-10/2018) using 50 mg DOX/10 mg mitomycin C emulsified 1:2 with ethiodized oil (Lipiodol). Peripheral blood was sampled at 10 timepoints for standard non-compartmental analysis of peak concentrations (Cmax) and area under the curve (AUC) with dose normalization (DN). Imaging markers included Lipiodol distribution on post-cTACE CT for patient stratification into 1 segment (n = 10), ≥ 2 segments (n = 10), and lobar cTACE (n = 10), and baseline enhancing tumor volume (ETV). Adverse events (AEs) and tumor response on MRI were recorded 3-4 weeks post-cTACE. Statistics included repeated measurement ANOVA (RM-ANOVA), Mann-Whitney, Kruskal-Wallis, Fisher's exact test, and Pearson correlation. RESULTS Hepatocellular (n = 26), cholangiocarcinoma (n = 1), and neuroendocrine metastases (n = 3) were included. Stratified according to Lipiodol distribution, DOX-Cmax increased from 1 segment (DOX-Cmax, 83.94 ± 75.09 ng/mL; DN-DOX-Cmax, 2.67 ± 2.02 ng/mL/mg) to ≥ 2 segments (DOX-Cmax, 139.66 ± 117.73 ng/mL; DN-DOX-Cmax, 3.68 ± 4.20 ng/mL/mg) to lobar distribution (DOX-Cmax, 334.35 ± 215.18 ng/mL; DN-DOX-Cmax, 7.11 ± 4.24 ng/mL/mg; p = 0.036). While differences in DN-DOX-AUC remained insignificant, RM-ANOVA revealed significant separation of time concentration curves for DOX (p = 0.023) and DOXOL (p = 0.041) comparing 1, ≥ 2 segments, and lobar cTACE. Additional indicators of higher DN-DOX-Cmax were high ETV (p = 0.047) and Child-Pugh B (p = 0.009). High ETV and tumoral Lipiodol coverage also correlated with tumor response. AE occurred less frequently after segmental cTACE. CONCLUSIONS This prospective clinical trial provides updated PK data revealing Lipiodol distribution as an imaging marker predictive of DOX-Cmax and tumor response after cTACE in liver cancer. KEY POINTS • Prospective pharmacokinetic analysis after conventional TACE revealed Lipiodol distribution (1 vs. ≥ 2 segments vs. lobar) as an imaging marker predictive of doxorubicin peak concentrations (Cmax). • Child-Pugh B class and tumor hypervascularization, measurable as enhancing tumor volume (ETV) at baseline, were identified as additional predictors for higher dose-normalized doxorubicin Cmax after conventional TACE. • ETV at baseline and tumoral Lipiodol coverage can serve as predictors of volumetric tumor response after conventional TACE according to quantitative European Association for the Study of the Liver (qEASL) criteria.
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Affiliation(s)
- Lynn J Savic
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
- Institute of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Eliot Funai
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Khaled Bousabarah
- Department of Stereotactic and Functional Neurosurgery, University Hospital of Cologne, Cologne, Germany
| | - Isabel T Schobert
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
- Institute of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Edvin Isufi
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | | | - Sophie Stark
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
- Institute of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Ping He
- Sidney Kimmel Comprehensive Cancer Center at Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Michelle A Rudek
- Sidney Kimmel Comprehensive Cancer Center at Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Juan Carlos Perez Lozada
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Rajasekhara Ayyagari
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Jeffrey Pollak
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Todd Schlachter
- Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
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40
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Zhang XH, Huo L, Liu CF, Xu F, Lu XY, Huang B, Jia NY, Wu L, Shen F. Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival. HPB (Oxford) 2020; 22:1197-1205. [PMID: 31843444 DOI: 10.1016/j.hpb.2019.11.008] [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: 08/27/2019] [Revised: 11/12/2019] [Accepted: 11/15/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. METHODS From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast-enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. RESULTS The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. CONCLUSION The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.
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Affiliation(s)
- Xiang-Hua Zhang
- The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lei Huo
- The Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Cai-Feng Liu
- The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Feng Xu
- The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xin-Yuan Lu
- The Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Bin Huang
- The Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ning-Yang Jia
- The Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| | - Lu Wu
- The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| | - Feng Shen
- The Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Abstract
Intrahepatic cholangiocarcinoma (ICC) arises from the epithelial cells of the intrahepatic and extrahepatic bile ducts and occurs proximal to the segmental biliary ducts. Risk factors include chronic hepatitis and cirrhosis, biliary inflammatory diseases, and hepatobiliary flukes, although in most cases, no known risk factor is identified. ICC is highly aggressive, with long-term survival only observed in patients with a complete R0 surgical resection. Technical and physiologic resectability should be considered when performing an operative plan. Nodal involvement is among the most important prognostic factors associated with survival and a porta hepatis lymphadenectomy should be performed at the time of resection. Adjuvant chemotherapy can provide a significant survival benefit for patients with more advanced or aggressive tumors. Systemic, locoregional, and targeted therapies exist for patients with unresectable or metastatic disease.
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Affiliation(s)
- Ramy El-Diwany
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, 320 W. 10th Avenue, M-260 Starling Loving Hall, Columbus, OH 43210, USA
| | - Aslam Ejaz
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA.
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42
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Lee J, Gangi A. Regional Therapies in Hepatocellular Carcinoma and Cholangiocarcinoma. CANCER REGIONAL THERAPY 2020:311-322. [DOI: 10.1007/978-3-030-28891-4_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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43
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Ferrone C, Goyal L, Qadan M, Gervais D, Sahani DV, Zhu AX, Hong TS, Blaszkowsky LS, Tanabe KK, Vangel M, Amorim BJ, Wo JY, Mahmood U, Pandharipande PV, Catana C, Duenas VP, Collazo YQ, Canamaque LG, Domachevsky L, Bernstine HH, Groshar D, Shih TTF, Li Y, Herrmann K, Umutlu L, Rosen BR, Catalano OA. Management implications of fluorodeoxyglucose positron emission tomography/magnetic resonance in untreated intrahepatic cholangiocarcinoma. Eur J Nucl Med Mol Imaging 2019; 47:1871-1884. [PMID: 31705172 DOI: 10.1007/s00259-019-04558-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis with surgical resection offering the best chance for long-term survival and potential cure. However, in up to 36% of patients who undergo surgery, more extensive disease is found at time of operation requiring cancellation of surgery. PET/MR is a novel hybrid technology that might improve local and whole-body staging in ICC patients, potentially influencing clinical management. This study was aimed to investigate the possible management implications of PET/MR, relative to conventional imaging, in patients affected by untreated intrahepatic cholangiocarcinoma. METHODS Retrospective review of the clinicopathologic features of 37 patients with iCCC, who underwent PET/MR between September 2015 and August 2018, was performed to investigate the management implications that PET/MR had exerted on the affected patients, relative to conventional imaging. RESULTS Of the 37 patients enrolled, median age 63.5 years, 20 (54%) were female. The same day PET/CT was performed in 26 patients. All patients were iCCC-treatment-naïve. Conventional imaging obtained as part of routine clinical care demonstrated early-stage resectable disease for 15 patients and advanced stage disease beyond the scope of surgical resection for 22. PET/MR modified the clinical management of 11/37 (29.7%) patients: for 5 patients (13.5%), the operation was cancelled due to identification of additional disease, while 4 "inoperable" patients (10.8%) underwent an operation. An additional 2 patients (5.4%) had a significant change in their operative plan based on PET/MR. CONCLUSIONS When compared with standard imaging, PET/MR significantly influenced the treatment plan in 29.7% of patients with iCCC. TRIAL REGISTRATION 2018P001334.
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Affiliation(s)
- Cristina Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Lipika Goyal
- Department of Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Debra Gervais
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA
| | - Dushyant V Sahani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA
| | - Andrew X Zhu
- Department of Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Lawrence S Blaszkowsky
- Department of Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA.,Department of Oncology, Newton-Wellesley Hospital, 2114 Washington St., Newton, MA, 02462, USA
| | - Kenneth K Tanabe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Mark Vangel
- Department of Biostatics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Barbara J Amorim
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA.,Division of Nuclear Medicine, State University of Campinas (UNICAMP), Campinas, Brazil
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA
| | - Umar Mahmood
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA.,Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th, Charlestown, MA, 02129, USA
| | - Pari V Pandharipande
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA
| | - Ciprian Catana
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th, Charlestown, MA, 02129, USA
| | - Virginia P Duenas
- Department of Nuclear Medicine and Radiology, Hospital HM Puerta del Sur, Avda Carlos V 70, 28938, Madrid, Spain
| | - Yolanda Q Collazo
- Department of Surgery, Hospital HM Sanchinarro, Avda Carlos V 70, 28938, Madrid, Spain
| | - Lina G Canamaque
- Department of Nuclear Medicine and Radiology, Hospital HM Puerta del Sur, Avda Carlos V 70, 28938, Madrid, Spain
| | - Liran Domachevsky
- Department of Radiology and Nuclear Medicine, Assuta Medical Center, HaBarzel St. 20, Tel Aviv-Yafo, Israel
| | - Hanna H Bernstine
- Department of Radiology and Nuclear Medicine, Assuta Medical Center, HaBarzel St. 20, Tel Aviv-Yafo, Israel
| | - David Groshar
- Department of Radiology and Nuclear Medicine, Assuta Medical Center, HaBarzel St. 20, Tel Aviv-Yafo, Israel
| | - Tiffany Tsing-Fang Shih
- Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, No. 7, Chung-Shan South Rd., Taipei, 10016, Taiwan
| | - Yan Li
- Department of Radiology, Universitatsklinikum, Essen University, Hufelandstraße 55, 45147, Essen, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, Universitatsklinikum, Essen University, Hufelandstraße 55, 45147, Essen, Germany
| | - Lale Umutlu
- Department of Radiology, Universitatsklinikum, Essen University, Hufelandstraße 55, 45147, Essen, Germany
| | - Bruce R Rosen
- Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th, Charlestown, MA, 02129, USA
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, WHT 270, 55 Fruit St., Boston, MA, 02114, USA. .,Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th, Charlestown, MA, 02129, USA. .,Department of Radiology, University of Naples "Parthenope", Via Acton 38, 80131, Naples, Italy.
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Cao WZ, Zhou ZQ, Jiang S, Li H, Niu W, Gao P, Li GJ, Chen F. Efficacy and safety of drug-eluting beads for transarterial chemoembolization in patients with advanced hepatocellular carcinoma. Exp Ther Med 2019; 18:4625-4630. [PMID: 31798699 DOI: 10.3892/etm.2019.8163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 09/26/2019] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has more recently become a leading cause of cancer-associated mortality worldwide. Particularly at an advanced stage, the prognosis is generally poor due to lack of effective treatments. Transarterial chemoembolization (TACE) is now a recognized therapy for advanced HCC, serving to deprive tumors of feeder arteries through induced ischemic necrosis. However, there is also a potential for undesired circulatory toxicity owing to drug reflux from tumor artery to surrounding healthy tissues. Although effective chemotherapeutic drug concentrations are thus lowered, the side effects of systemic chemotherapy are aggravated. The mid-2000 emergence of drug-eluting beads (DEB) loaded with anti-neoplastic drugs has proven particularly advantageous, enabling localized treatment and directed delivery of chemotherapeutics. DEB-TACE (dTACE) augments local infusion of anti-neoplastic agents to prolong agent/tumor contact, expanding upon conventional TACE. At present, data on DEB use in China are limited, particularly in terms of proprietary microspheres (CalliSpheres; Hengrui Medicine Co.). To explore the efficacy and safety of CalliSpheres, A total of 90 patients receiving this means of dTACE for advanced HCC were assessed in the present study. Clinical efficacy was evaluated based on tumor response and overall survival rates using the National Cancer Institute Common Terminology Criteria for Adverse Events to assess tolerability. The satisfactory tumor response and acceptable tolerability demonstrated in the follow-up confirm the promising utility of CalliSpheres in treating patients with advanced HCC.
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Affiliation(s)
- Wen-Zhen Cao
- Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Zhu-Qian Zhou
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Song Jiang
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Hao Li
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Wei Niu
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Peng Gao
- Medical Research Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Gui-Jie Li
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Feng Chen
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
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Chemoembolization with Degradable Starch Microspheres for Treatment of Patients with Primary or Recurrent Unresectable, Locally Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study. Cardiovasc Intervent Radiol 2019; 42:1709-1717. [PMID: 31578633 DOI: 10.1007/s00270-019-02344-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Revised: 09/08/2019] [Accepted: 09/18/2019] [Indexed: 01/04/2023]
Abstract
PURPOSE To evaluate efficacy and complication rates of TACE with degradable starch microspheres (DSM-TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) with or without prior major liver resection (MLR). METHODS This is a retrospective single-center study on 21 patients (age 63 ± 15 years) with either unresectable ICC progressive under systemic chemotherapy or unresectable intrahepatic tumor recurrence after prior MLR. Patients were treated by multi-agent (cisplatin/doxorubicin/mitomycin C) DSM-TACE between August 2012 and July 2016, repeated 3 times at 4-week intervals. Imaging response was evaluated using RECIST 1.1. Overall survival (OS) and complication rates, stratified by history of MLR, were investigated. RESULTS Patients underwent a total 64 DSM-TACE sessions. Two patients (without MLR) were lost to follow-up after one uneventful DSM-TACE session. One patient underwent living-donor-liver transplantation after one DSM-TACE-session yielding partial remission. Of the remaining 18 patients, imaging response according to RECIST 1.1 was: complete remission in 2/18 (11.1%); PR in 9/18 (50%), and stable disease in 7/18 (38.9%), yielding an objective response rate of 61.1% and a disease control rate of 100%. Median OS of patients with objective response was significantly longer (18.0 months) than that of survival of patients with stable disease (4.8 months) (p = 0.001). Median OS of patients with MLR (12.5 months) was similar to that of patients without MLR (13.2 months). Of 21 patients, 2 (9.5%) developed post-interventional hepatobiliary abscesses, and one of these patients died due to subsequent sepsis. CONCLUSION DSM-TACE is an effective treatment for unresectable and otherwise therapy-refractory intrahepatic cholangiocarcinoma, even in those patients with intrahepatic disease recurrence after prior MLR. LEVEL OF EVIDENCE Level II, therapeutic study.
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46
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Mondaca S, Yarmohammadi H, Kemeny NE. Regional Chemotherapy for Biliary Tract Tumors and Hepatocellular Carcinoma. Surg Oncol Clin N Am 2019; 28:717-729. [PMID: 31472915 DOI: 10.1016/j.soc.2019.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Locally advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma are associated with a grim prognosis. The development of highly effective systemic therapies for these tumors has been challenging; however, numerous locoregional treatment alternatives have emerged, including transarterial hepatic embolization (TAE), transarterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), hepatic arterial infusion chemotherapy (HAI), radioembolization, and stereotactic body radiation therapy. Although there is potential for long-term disease control for these therapies, the evidence to guide adequate patient selection and choose among different treatment alternatives is still limited. This review focuses on the rationale and data supporting TAE, TACE, DEB-TACE, and HAI in hepatobiliary cancers.
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Affiliation(s)
- Sebastian Mondaca
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Hooman Yarmohammadi
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Nancy E Kemeny
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
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47
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Repeated Treatment with 90Y-Microspheres in Intrahepatic Cholangiocarcinoma Relapsed After the First Radioembolization. Cancer Biother Radiopharm 2019; 34:231-237. [DOI: 10.1089/cbr.2018.2718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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48
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Adeva J, Sangro B, Salati M, Edeline J, La Casta A, Bittoni A, Berardi R, Bruix J, Valle JW. Medical treatment for cholangiocarcinoma. Liver Int 2019; 39 Suppl 1:123-142. [PMID: 30892822 DOI: 10.1111/liv.14100] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 03/10/2019] [Accepted: 03/12/2019] [Indexed: 02/13/2023]
Abstract
Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention-to-treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first-line treatment of patients with advanced disease; there is no established second-line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on-target therapeutic options are under active investigation. The most developed are studies targeting IDH-1 (isocitrate dehydrogenase) mutations and FGFR-2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed.
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Affiliation(s)
- Jorge Adeva
- Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain
| | - Maximiliano Salati
- Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena, Italy.,Division of Molecular Pathology, Institute of Cancer Research and Gastrointestinal Unit, Royal Marsden Hospital, London and Sutton, UK
| | - Julien Edeline
- Department of Medical Oncology, Centre Eugene Marquis, Rennes, France
| | - Adelaida La Casta
- Department of Medical Oncology, Hospital Universitario Donostia, Navarra, Spain
| | - Alessandro Bittoni
- Clinica Oncologica, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy
| | - Rosanna Berardi
- Clinica Oncologica, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Manchester, UK.,Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
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Yttrium-90 Radioembolization Is Cost Effective in Intrahepatic Cholangiocarcinoma: A SEER Medicare Population Study. J Vasc Interv Radiol 2019; 30:293-297. [PMID: 30819468 DOI: 10.1016/j.jvir.2018.07.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 07/18/2018] [Accepted: 07/30/2018] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. MATERIALS AND METHODS Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. RESULTS The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). CONCLUSIONS Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.
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50
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Zhuang L, Yan X, Meng Z. Second primary malignancy in patients with cholangiocarcinoma: a population-based study. Cancer Manag Res 2019; 11:1969-1983. [PMID: 30881122 PMCID: PMC6402443 DOI: 10.2147/cmar.s187614] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background A population-based estimate of risk of second primary malignancy (SPM) in patients with cholangiocarcinoma (CCA) is still lacking. Objectives To investigate the overall and site-specific risk of SPM in patients with CCA. To identify risk factors of SPM and further evaluate the impact of SPM on overall survival (OS) and disease specific survival (DSS) in patients with CCA. Methods Patients with histologically diagnosed CCA between 1973 and 2015 were identified from the Surveillance, Epidemiology and End Results database. Standardized incidence ratio (SIR) was calculated. Risk factors for SPM and CCA survival were evaluated by logistic, Cox, and nomogram methods. Results We found that the overall risk of SPM in patients with CCA was significantly higher than that in the general population (SIR =1.27, 95% CI =1.03–1.55, P<0.05). The risk of SPM was significantly increased at specific sites, including transverse colon, intrahepatic bile duct, other biliary, and thyroid. A significant increase in overall risk was characterized in the subgroups of patients aged ≤29, patients aged 30–59 years, females, whites, and patients with latency ≤11 months (63.41, 2.45, 1.4, 1.3, and 2.6-fold, respectively). In patients with CCA, not having undergone surgery for the first primary malignancy (vs having undergone surgery for the first primary malignancy; HR =0.269; 95% CI =0.211–0.342; P<0.001) was associated with significantly decreased risk of SPM. Patients with SPM had better OS and DSS than those without SPM (Log rank P<0.001). Absence of SPM was an independent risk factor for poorer OS and DSS. Conclusion Although the risk of SPM in patients with CCA was significantly increased, the presence of SPM did not shorten OS and DSS of patients with CCA, possibly due to the relatively poorer survival of patients with CCA.
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Affiliation(s)
- Liping Zhuang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
| | - Xia Yan
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
| | - Zhiqiang Meng
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
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