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Rousian M, van Verschuer V, Franssen S, Bijdevaate D, Bokkers RPH, Braat AE, de Bruijne J, Bruno MJ, Burgmans MC, van Delden OM, Dewulf M, Erdmann JI, Hagendoorn J, van der Holt B, Hoogwater FJH, Inderson A, van der Leij C, Mohseny B, Poley JW, Smits MLJ, van Vilsteren FGI, Voermans RP, Zijlstra IAJ, van Driel LMJW, Koerkamp BG. Primary percutaneous stenting above the ampulla versus endoscopic drainage for unresectable malignant hilar biliary obstruction (TESLA RCT): study protocol for a multicenter randomized controlled trial. BMC Cancer 2025; 25:849. [PMID: 40346549 PMCID: PMC12063260 DOI: 10.1186/s12885-025-14158-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Accepted: 04/15/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Patients with malignant hilar biliary obstruction typically present with painless jaundice. They commonly have perihilar cholangiocarcinoma (pCCA), but also intrahepatic cholangiocarcinoma, gallbladder cancer, and metastases to the liver hilum can present with hilar biliary obstruction. Endoscopic biliary drainage is the standard of care in most centers. Many patients develop drainage-related complications after endoscopic biliary drainage for malignant hilar biliary obstruction, in particular cholangitis, resulting in reinterventions, clinical deterioration and a high mortality rate. Primary percutaneous stenting (PPS) aims to avoid bacterial contamination and reduce drainage-related complications. The aim of this randomized controlled trial is to compare PPS with endoscopic biliary drainage in patients with unresectable malignant hilar biliary obstruction. METHODS This multicenter phase 3 randomized controlled trial (TESLA RCT) will recruit 148 patients with unresectable malignant hilar biliary obstruction in six Dutch tertiary academic referral centers. Diagnosis of malignant hilar biliary obstruction is pathologically confirmed or determined as very likely by the multidisciplinary team. In the intervention arm, patients undergo primary percutaneous stenting with uncovered self-expandable metal stents without crossing the ampulla and without leaving an external drain. In the control arm patients undergo endoscopic biliary drainage according to international guidelines. The primary endpoint is major complications within 90 days after randomization. Secondary outcomes include technical success, reintervention rates, decrease of bilirubin levels, eligibility for palliative systemic treatment, quality of life, and overall survival. DISCUSSION The multicenter TESLA RCT compares primary percutaneous stenting with endoscopic biliary drainage in patients with unresectable malignant hilar biliary obstruction. First patient was randomized on August 9, 2023. TRIAL REGISTRATION Netherlands Trial Register (NL-OMON53463), registered on May 12, 2023, and Clinicaltrials.gov (NCT06671418), registered on November 1, 2024.
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Affiliation(s)
- M Rousian
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - V van Verschuer
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - S Franssen
- Department of Radiology, UMC Utrecht, University Medical Center, Utrecht, The Netherlands
| | - D Bijdevaate
- Department of Interventional Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - R P H Bokkers
- Department of Interventional Radiology, UMC Groningen, University Medical Center, Groningen, The Netherlands
| | - A E Braat
- Department of Surgery, Leiden UMC, University Medical Center, Leiden, The Netherlands
| | - J de Bruijne
- Department of Gastroenterology and Hepatology, UMC Utrecht, University Medical Center, Utrecht, The Netherlands
| | - M J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - M C Burgmans
- Department of Interventional Radiology, Leiden UMC, University Medical Center, Leiden, The Netherlands
| | - O M van Delden
- Department of Gastroenterology and Hepatology, Amsterdam University Medical center, University of Amsterdam, Amsterdam, The Netherlands
| | - M Dewulf
- Department of Surgery, Maastricht UMC, University Medical Center, Maastricht, The Netherlands
| | - J I Erdmann
- Department of Surgery, Amsterdam University Medical center, University of Amsterdam, Amsterdam, The Netherlands
| | - J Hagendoorn
- Department of Surgery, UMC Utrecht, University Medical Center, Utrecht, The Netherlands
| | - B van der Holt
- Department of Hematology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - F J H Hoogwater
- Department of Surgery, UMC Groningen, University Medical Center, Groningen, The Netherlands
| | - A Inderson
- Department of Gastroenterology and Hepatology, Leiden UMC, University Medical Center, Leiden, The Netherlands
| | - C van der Leij
- Department of Interventional Radiology, Maastricht UMC, University Medical Center, Maastricht, The Netherlands
| | - B Mohseny
- Department of Interventional Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - J W Poley
- Department of Gastroenterology and Hepatology, Maastricht UMC, University Medical Center, Maastricht, The Netherlands
| | - M L J Smits
- Department of Interventional Radiology, UMC Utrecht, University Medical Center, Utrecht, The Netherlands
| | - F G I van Vilsteren
- Department of Gastroenterology and Hepatology, UMC Groningen, University Medical Center, Groningen, The Netherlands
| | - R P Voermans
- Department of Gastroenterology and Hepatology, Amsterdam University Medical center, University of Amsterdam, Amsterdam, The Netherlands
| | - I A J Zijlstra
- Department of Interventional Radiology, Amsterdam University Medical center, University of Amsterdam, Amsterdam, The Netherlands
| | - L M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - B Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
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Nooijen LE, de Boer MT, Braat AE, Dewulf M, den Dulk M, Hagendoorn J, Hoogwater FJH, Lam HD, Molenaar Q, Neumann U, Porte RJ, Swijnenburg RJ, Zonderhuis B, Kazemier G, Klümpen HJ, van Gulik T, Groot Koerkamp B, Erdmann JI. National consensus on a new resectability classification for perihilar cholangiocarcinoma - A modified Delphi method. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:107117. [PMID: 37880001 DOI: 10.1016/j.ejso.2023.107117] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 10/03/2023] [Accepted: 10/10/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study. METHOD Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed. RESULTS The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease. CONCLUSION This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.
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Affiliation(s)
- Lynn E Nooijen
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Marieke T de Boer
- University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands
| | | | - Maxime Dewulf
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | - Marcel den Dulk
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | | | | | - Hwai-Ding Lam
- LUMC, Department of Surgery, Leiden, the Netherlands
| | | | - Ulf Neumann
- Maastricht UMC, Department of Surgery, Maastricht, the Netherlands
| | - Robert J Porte
- University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands
| | - Rutger-Jan Swijnenburg
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Babs Zonderhuis
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Geert Kazemier
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Heinz-Josef Klümpen
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Thomas van Gulik
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Bas Groot Koerkamp
- Erasmus MC Cancer Institute, Department of Surgery, Rotterdam, the Netherlands
| | - Joris I Erdmann
- Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands; Amsterdam UMC, Location Universiteit van Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
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Hu M, Xu D, Zhang Y, Li A, Li X, Huang J. Efficacy and safety of robotic surgery versus open surgery for hilar cholangiocarcinoma: a systematic review and meta-analysis. Int J Surg 2025; 111:1301-1310. [PMID: 39037741 PMCID: PMC11745663 DOI: 10.1097/js9.0000000000001952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 07/07/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVE The aim is to assess and contrast the effectiveness and safety of employing robotic surgery versus traditional open surgery in managing cases of hilar cholangiocarcinoma. METHODS Computer searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database to identify case-control studies comparing robotic surgery with traditional open surgery in the treatment of hilar cholangiocarcinoma from inception until July 2023. References from retrieved articles were reviewed to broaden the search. This review was prospectively registered in the PROSPERO database (PROSPERO ID: CRD42024527511) and reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. The primary outcome measures included operation time, intraoperative blood transfusion rate, R0 resection rate, lymph node metastasis rate, incidence of postoperative complications, and postoperative hospital stay. Data analysis was performed using RevMan 5.4 software, calculating combined odds ratios (OR), mean differences (MD), and 95% CI. RESULTS A total of 4 studies encompassing 267 patients diagnosed with hilar cholangiocarcinoma (177 males and 90 females, mean age of (58.8±5.7) years) were included in this analysis. Among these, 165 patients underwent open surgery, while 102 patients underwent robotic surgery. The results of the meta-analysis demonstrated comparable outcomes between the two groups. Specifically, the operation time between the robotic surgery and open surgery cohorts did not significantly differ (MD=-103.96, 95% CI: -216.90 to 8.98, P = 0.070 ). Additionally, the intraoperative blood transfusion rate (OR=1.32, 95% CI: 0.43-4.07, P =0.630), R0 resection rate (OR=1.41, 95% CI: 0.71-2.81, P=0.330 ), and lymph node metastasis rate (OR=1.62, 95% CI: 0.46-5.63, P=0.450 ) showed no significant differences between the groups. Similarly, there were no statistically significant disparities observed in the incidence of postoperative complications (OR=0.60, 95% CI: 0.28-1.31, P=0.200 ) and postoperative hospital stay (MD=2.17, 95% CI: -11.56 to 15.90, P=0.760 ). CONCLUSION In the treatment of hilar cholangiocarcinoma, robotic surgery demonstrates comparable safety and feasibility to traditional open surgery. However, due to the limited quantity and quality of the included studies, these conclusions warrant validation through additional high-quality investigations.
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Affiliation(s)
| | | | | | | | | | - Jie Huang
- The Third Division of Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China
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Renteria Ramirez DE, Knøfler LA, Kirkegård J, Fristrup CW, Stender MT, Nielsen SD, Markussen A, Larsen PN, Akdag D, Al-Saffar HA, Pommergaard HC. Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study. Cancer Epidemiol 2024; 93:102688. [PMID: 39418943 DOI: 10.1016/j.canep.2024.102688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 10/08/2024] [Accepted: 10/12/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Biliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT). However, standardized practices for BTC are lacking, and there is a need to assess the impact of current MDT treatment decisions on BTC outcomes. The purpose of this study was to investigate the role of the treatment plan proposed by the first MDT conference on survival in patients with BTC, and to identify risk factors for poor survival in this population. METHOD This nationwide, multicenter, retrospective cohort study examined data from the Danish Liver Cancer Group (2013-2020) with confirmed BTC diagnoses. Multiple imputation was used to handle missing data. Survival and variable-survival rate relationships were analyzed using the Kaplan-Meier estimator, and the Cox regression model, respectively. RESULTS Eligible BTC-confirmed cases: n=1923. The overall median survival was 7.7 months (95 % CI: 7.1-8.5), with a 5-year survival rate of 16.3 %. Patients over 70 years of age, with ECOG-PS 3 or 4, non-operable cases, and with unresectable tumors had lower survival rates. Surgery as the first therapeutic option showed the highest median survival (33.1 months, 95 % CI: 27.2-41.6; p < 0.0001). Multivariable analysis showed that poor ECOG-PS, palliative and neoadjuvant chemotherapy, stereotactic radiotherapy, and best supportive care significantly increased mortality risk in patients with BTC (p=0.05). CONCLUSION Among the therapeutic options prescribed by the MDT for patients with BTC, surgery offered the best survival rates, likely due to patient-related prognostic factors. High ECOG-PS was linked to an increased mortality risk regardless of age, highlighting the importance of this criterion in treatment decisions.
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Affiliation(s)
- D E Renteria Ramirez
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - L A Knøfler
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - J Kirkegård
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - C W Fristrup
- Department of Surgery, Odense University Hospital, Odense, Denmark
| | - M T Stender
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - S D Nielsen
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute for Clinical Medicine, University of Copenhagen, Panum Institute, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - A Markussen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Denmark
| | - P N Larsen
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - D Akdag
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - H A Al-Saffar
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - H C Pommergaard
- Hepatic Malignancy Surgical Research Unit (HEPSURU), Department of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute for Clinical Medicine, University of Copenhagen, Panum Institute, Copenhagen, Denmark.
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Ceriani R, Colapietro F, Gabbiadini R, Buono AD, Pugliese N, Masetti C, Brandaleone L, Ierace T, Solbiati L. Ultrasound-guided percutaneous biopsy for challenging perihilar focal liver lesions: diagnostic accuracy and safety assessment. J Ultrasound 2024:10.1007/s40477-024-00949-x. [PMID: 39487923 DOI: 10.1007/s40477-024-00949-x] [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: 05/10/2024] [Accepted: 07/24/2024] [Indexed: 11/04/2024] Open
Abstract
PURPOSE In cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions. METHODS We included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023. RESULTS All samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported. CONCLUSION US-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.
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Affiliation(s)
- Roberto Ceriani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy.
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Roberto Gabbiadini
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Arianna Dal Buono
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Chiara Masetti
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Luca Brandaleone
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Tiziana Ierace
- Department of Radiology, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milano, Italy
| | - Luigi Solbiati
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Radiology, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milano, Italy
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Wang J, Shi R, Yin Y, Luo H, Cao Y, Lyu Y, Luo H, Zeng X, Wang D. Clinical significance of small extracellular vesicles in cholangiocarcinoma. Front Oncol 2024; 14:1334592. [PMID: 38665948 PMCID: PMC11043544 DOI: 10.3389/fonc.2024.1334592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/28/2024] [Indexed: 04/28/2024] Open
Abstract
Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.
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Affiliation(s)
- Jianjun Wang
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Ruizi Shi
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yuan Yin
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Hua Luo
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yuan Cao
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yun Lyu
- Departmant of Oncology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Huiwen Luo
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Xintao Zeng
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Decai Wang
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
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Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
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Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
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8
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Wang J, Xia Y, Cao Y, Zeng X, Luo H, Cai X, Shi M, Luo H, Wang D. Safety and feasibility of laparoscopic radical resection for bismuth types III and IV hilar cholangiocarcinoma: a single-center experience from China. Front Oncol 2023; 13:1280513. [PMID: 38188306 PMCID: PMC10766688 DOI: 10.3389/fonc.2023.1280513] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/29/2023] [Indexed: 01/09/2024] Open
Abstract
Background Surgery represents the only cure for hilar cholangiocarcinoma (HC). However, laparoscopic radical resection remains technically challenging owing to the complex anatomy and reconstruction required during surgery. Therefore, reports on laparoscopic surgery (LS) for HC, especially for types III and IV, are limited. This study aimed to evaluate the safety and feasibility of laparoscopic radical surgery for Bismuth types III and IV HC. Methods The data of 16 patients who underwent LS and 9 who underwent open surgery (OS) for Bismuth types III and IV HC at Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, between December 2017 and January 2022 were analyzed. Basic patient information, Bismuth-Corlette type, AJCC staging, postoperative complications, pathological findings, and follow-up results were evaluated. Results Sixteen patients underwent LS and 9 underwent OS for HC. According to the preoperative imaging data, there were four cases of Bismuth type IIIa, eight of type IIIb, and four of type IV in the LS group and two of type IIIa, four of type IIIb, and three of type IV in the OS group (P>0.05). There were no significant differences in age, sex, ASA score, comorbidity, preoperative percutaneous transhepatic biliary drainage rate, history of abdominal surgery, or preoperative laboratory tests between the two groups (P>0.05). Although the mean operative time and mean intraoperative blood loss were higher in the LS group than in OS group, the differences were not statistically significant (P=0.121 and P=0.115, respectively). Four patients (25%) in the LS group and two (22.2%) in the OS group experienced postoperative complications (P>0.05). No significant differences were observed in other surgical outcomes and pathologic findings between the two groups. Regarding the tumor recurrence rate, there was no difference between the groups (P>0.05) during the follow-up period (23.9 ± 13.3 months vs. 17.8 ± 12.3 months, P=0.240). Conclusion Laparoscopic radical resection of Bismuth types III and IV HC remains challenging, and extremely delicate surgical skills are required when performing extended hemihepatectomy followed by complex bilioenteric reconstructions. However, this procedure is generally safe and feasible for hepatobiliary surgeons with extensive laparoscopy experience.
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Affiliation(s)
- Jianjun Wang
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yang Xia
- Department of Neurosurgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yuan Cao
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Xintao Zeng
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Hua Luo
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Xianfu Cai
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Mingsong Shi
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Huiwen Luo
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Decai Wang
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
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9
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Song Y, Zhou G, Zhou Y, Xu Y, Zhang J, Zhang K, He P, Chen M, Liu Y, Sun J, Hu C, Li M, Liao M, Zhang Y, Liao W, Zhou Y. Artificial intelligence CT radiomics to predict early recurrence of intrahepatic cholangiocarcinoma: a multicenter study. Hepatol Int 2023; 17:1016-1027. [PMID: 36821045 DOI: 10.1007/s12072-023-10487-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/13/2023] [Indexed: 02/24/2023]
Abstract
OBJECTIVES In this multicenter study, we sought to develop and validate a preoperative model for predicting early recurrence (ER) risk after curative resection of intrahepatic cholangiocarcinoma (ICC) through artificial intelligence (AI)-based CT radiomics approach. MATERIALS AND METHODS A total of 311 patients (Derivation: 160; Internal and two external validations: 36, 74 and 61) from 8 medical centers who underwent curative resection were collected retrospectively. In derivation cohort, radiomics and clinical-radiomics models for ER prediction were constructed by LightGBM (a machine learning algorithm). A clinical model was also developed for comparison. Model performance was validated in internal and two external cohorts by ROC. In addition, we investigated the interpretability of the LightGBM model. RESULTS The combined clinical-radiomics model that included 15 radiomic features and 3 clinical features (CA19-9 > 1000 U/ml, vascular invasion and tumor margin), resulting in the area under the curves (AUCs) of 0.974 (95% CI 0.946-1.000) in the derivation cohort, and 0.871-0.882 (95% CI 0.672-0.962) in the internal and external validation cohorts, respectively, which are higher than the AJCC 8th TNM staging system (AUCs: 0.686-0.717, p all < 0.05). Especially, the sensitivity of this machine learning model could reach 94.6% on average for all the cohorts. CONCLUSIONS This AI-driven combined radiomics model may provide as a useful tool to preoperatively predict ER and improve therapeutic management of ICC patients.
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Affiliation(s)
- Yangda Song
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Guangyao Zhou
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Yucheng Zhou
- Department of General Surgery, Hospital of Integrated TCM and Western Medicine, Southern Medical University, Guangzhou, 510315, China
| | - Yikai Xu
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jing Zhang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ketao Zhang
- Department of Hepatobiliary Surgery, Shunde Hospital of Southern Medical University, Foshan, 528308, Guangdong, China
| | - Pengyuan He
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Maowei Chen
- Department of Infectious Diseases, Wuming Hospital of Guangxi Medical University, Nanning, 530199, Guangxi, China
| | - Yanping Liu
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Gastroenterology, Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China
| | - Jiarun Sun
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Chengguang Hu
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
| | - Meng Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Minjun Liao
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | | | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, China.
| | - Yuanping Zhou
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, China.
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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10
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Gunchick V, McDevitt RL, Choi E, Winslow K, Zalupski MM, Sahai V. Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy. Oncologist 2023; 28:531-541. [PMID: 37036699 PMCID: PMC10243793 DOI: 10.1093/oncolo/oyad063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 02/08/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Patients with advanced biliary tract cancers (BTCs) have poor prognoses and limited therapeutic options. Renin-angiotensin antagonists (ACE-I/ARBs), statins, and aspirin may have potential anti-tumorigenic effects and decrease mortality per retrospective analyses in some solid tumors. OBJECTIVE To evaluate the efficacy of ACE-Is/ARBs, statins, and/or aspirin concurrent to first-line systemic therapy in patients with advanced or metastatic BTC. METHODS Adult patients at University of Michigan with pathologic confirmation of BTC between January 2010 and December 2020 were included in this retrospective analysis. RESULTS Of 1140 patients who met eligibility, a total of 509 patients received one or more concomitant medication(s) of interest in conjunction with systemic therapy for advanced cancer. In the total cohort, the overall survival for locally advanced patients (N = 305) was 16.3 months (95% CI: 12.1-18.6), and metastatic patients (N = 512) 8.6 months (95% CI: 7.6-9.5); P < .0001. Within this concomitant medication cohort, patients with locally advanced stage (n = 132) experienced significantly longer progression-free survival (9.8 vs 4.5; P < 0.0001), and overall survival (17.4 vs 10.6; P < 0.0001) than those with metastatic (n = 297) cancer, respectively. Patients who received ACE-Is/ARBs, statins, and/or aspirin (n = 245) versus not (n = 264) concurrent with systemic anti-cancer therapy did not experience improved progression-free (5.5 vs 5.5 months; hazard ratio (HR) 1.1; P = 0.51), or overall survival (12.3 vs 12.6 months; HR 1.1; P = 0.18), respectively. CONCLUSION In contrast to prior studies, no progression free or overall survival benefit in patients with advanced BTC from concurrent use of ACE-I/ARBs, statin, and/or aspirin with systemic therapy was observed when assessed by BTC subtype or specific systemic therapy regimen.
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Affiliation(s)
- Valerie Gunchick
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Rachel L McDevitt
- College of Pharmacy, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Elizabeth Choi
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Katherine Winslow
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Mark M Zalupski
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Vaibhav Sahai
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
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11
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Wang D, Pan B, Huang JC, Chen Q, Cui SP, Lang R, Lyu SC. Development and validation of machine learning models for predicting prognosis and guiding individualized postoperative chemotherapy: A real-world study of distal cholangiocarcinoma. Front Oncol 2023; 13:1106029. [PMID: 37007095 PMCID: PMC10050553 DOI: 10.3389/fonc.2023.1106029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 02/27/2023] [Indexed: 03/17/2023] Open
Abstract
BACKGROUND Distal cholangiocarcinoma (dCCA), originating from the common bile duct, is greatly associated with a dismal prognosis. A series of different studies based on cancer classification have been developed, aimed to optimize therapy and predict and improve prognosis. In this study, we explored and compared several novel machine learning models that might lead to an improvement in prediction accuracy and treatment options for patients with dCCA. METHODS In this study, 169 patients with dCCA were recruited and randomly divided into the training cohort (n = 118) and the validation cohort (n = 51), and their medical records were reviewed, including survival outcomes, laboratory values, treatment strategies, pathological results, and demographic information. Variables identified as independently associated with the primary outcome by least absolute shrinkage and selection operator (LASSO) regression, the random survival forest (RSF) algorithm, and univariate and multivariate Cox regression analyses were introduced to establish the following different machine learning models and canonical regression model: support vector machine (SVM), SurvivalTree, Coxboost, RSF, DeepSurv, and Cox proportional hazards (CoxPH). We measured and compared the performance of models using the receiver operating characteristic (ROC) curve, integrated Brier score (IBS), and concordance index (C-index) following cross-validation. The machine learning model with the best performance was screened out and compared with the TNM Classification using ROC, IBS, and C-index. Finally, patients were stratified based on the model with the best performance to assess whether they benefited from postoperative chemotherapy through the log-rank test. RESULTS Among medical features, five variables, including tumor differentiation, T-stage, lymph node metastasis (LNM), albumin-to-fibrinogen ratio (AFR), and carbohydrate antigen 19-9 (CA19-9), were used to develop machine learning models. In the training cohort and the validation cohort, C-index achieved 0.763 vs. 0.686 (SVM), 0.749 vs. 0.692 (SurvivalTree), 0.747 vs. 0.690 (Coxboost), 0.745 vs. 0.690 (RSF), 0.746 vs. 0.711 (DeepSurv), and 0.724 vs. 0.701 (CoxPH), respectively. The DeepSurv model (0.823 vs. 0.754) had the highest mean area under the ROC curve (AUC) than other models, including SVM (0.819 vs. 0.736), SurvivalTree (0.814 vs. 0.737), Coxboost (0.816 vs. 0.734), RSF (0.813 vs. 0.730), and CoxPH (0.788 vs. 0.753). The IBS of the DeepSurv model (0.132 vs. 0.147) was lower than that of SurvivalTree (0.135 vs. 0.236), Coxboost (0.141 vs. 0.207), RSF (0.140 vs. 0.225), and CoxPH (0.145 vs. 0.196). Results of the calibration chart and decision curve analysis (DCA) also demonstrated that DeepSurv had a satisfactory predictive performance. In addition, the performance of the DeepSurv model was better than that of the TNM Classification in C-index, mean AUC, and IBS (0.746 vs. 0.598, 0.823 vs. 0.613, and 0.132 vs. 0.186, respectively) in the training cohort. Patients were stratified and divided into high- and low-risk groups based on the DeepSurv model. In the training cohort, patients in the high-risk group would not benefit from postoperative chemotherapy (p = 0.519). In the low-risk group, patients receiving postoperative chemotherapy might have a better prognosis (p = 0.035). CONCLUSIONS In this study, the DeepSurv model was good at predicting prognosis and risk stratification to guide treatment options. AFR level might be a potential prognostic factor for dCCA. For the low-risk group in the DeepSurv model, patients might benefit from postoperative chemotherapy.
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Affiliation(s)
| | | | | | | | | | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Capital Medical University, Beijing, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Capital Medical University, Beijing, China
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12
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Patrono D, Colli F, Colangelo M, De Stefano N, Apostu AL, Mazza E, Catalano S, Rizza G, Mirabella S, Romagnoli R. How Can Machine Perfusion Change the Paradigm of Liver Transplantation for Patients with Perihilar Cholangiocarcinoma? J Clin Med 2023; 12:jcm12052026. [PMID: 36902813 PMCID: PMC10004136 DOI: 10.3390/jcm12052026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.
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13
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Páez-Carpio A, Hessheimer A, Bermúdez P, Zarco FX, Serrano E, Moreno J, Molina V, Ausania F, Carrero E, Burrel M, Fondevila C, Gómez FM. Percutaneous transhepatic biliary drainage for biliary obstruction in perihilar cholangiocarcinoma: a 10-year analysis of safety and outcomes using the CCI index. Langenbecks Arch Surg 2023; 408:109. [PMID: 36847837 DOI: 10.1007/s00423-023-02852-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/21/2023] [Indexed: 03/01/2023]
Abstract
PURPOSE To evaluate percutaneous transhepatic biliary drainage (PTBD) safety and efficacy in patients with perihilar cholangiocarcinoma (PCCA). METHODS This retrospective observational study included patients with PCCA and obstructive cholestasis referred for a PTBD in our institution between 2010 and 2020. Technical and clinical success rates and major complication and mortality rates one month after PTBD were used as main variables. Patients were divided and analyzed into two groups: > 30 and < 30 Comprehensive Complication Index (CCI). We also evaluated post-surgical outcomes in patients undergoing surgery. RESULTS Out of 223 patients, 57 were included. Technical success rate was 87.7%. Clinical success at 1 week was 83.6%, before surgery 68.2%, 80.0% at 2 weeks and 86.7% at 4 weeks. Mean total bilirubin (TBIL) values were 15.1 mg/dL (baseline), 8.1 mg/dL one week after PTBD), 6.1 mg/dL (2 weeks) and 2.1 mg/dL (4 weeks). Major complication rate was 21.1%. Three patients died (5.3%). Risk factors for major complications after the statistical analysis were: Bismuth classification (p = 0.01), tumor resectability (p = 0.04), PTBD clinical success (p = 0.04), TBIL 2 weeks after PTBD (p = 0.04), a second PTBD (p = 0.01), total PTBDs (p = 0.01) and duration of drainage (p = 0.03). Major postoperative complication rate in patients who underwent surgery was 59.3%, with a median CCI of 26.2. CONCLUSION PTBD is safe and effective in the management of biliary obstruction caused by PCCA. Bismuth classification, locally advanced tumors, and failure to achieve clinical success in the first PTBD are factors related to major complications. Our sample reported a high major postoperative complication rate, although with an acceptable median CCI.
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Affiliation(s)
- Alfredo Páez-Carpio
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain.
| | - Amelia Hessheimer
- General and Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, 28046, Madrid, Spain
| | - Patricia Bermúdez
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Federico X Zarco
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Elena Serrano
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Julián Moreno
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Víctor Molina
- General and Digestive Surgery Service, Hospital de La Santa Creu I Sant Pau, 08035, Barcelona, Spain
| | - Fabio Ausania
- General and Digestive Surgery Service, ICEDM, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Enrique Carrero
- Department of Anesthesiology, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Marta Burrel
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
| | - Constantino Fondevila
- General and Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, 28046, Madrid, Spain
| | - Fernando M Gómez
- Department of Radiology, CDI, Hospital Clínic Barcelona, 08036, Barcelona, Spain
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14
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Vatankhah F, Salimi N, Khalaji A, Baradaran B. Immune checkpoints and their promising prospect in cholangiocarcinoma treatment in combination with other therapeutic approaches. Int Immunopharmacol 2023; 114:109526. [PMID: 36481527 DOI: 10.1016/j.intimp.2022.109526] [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: 10/10/2022] [Revised: 11/21/2022] [Accepted: 11/27/2022] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma (CCA) is one of the malignant tumors that has shown rapid development in incidence and mortality in recent years. Like other types of cancer, patients with CCA experience alterations in the expression of immune checkpoints, indicating the importance of immune checkpoint inhibitors in treating CCA. The results of TCGA analysis in this study revealed a marginal difference in the expression of important immune checkpoints, Programmed cell death 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and their ligands in CCA samples compared to normal ones. This issue showed the importance of combination therapy in this cancer. This review considers CCA treatment and covers several therapeutic modalities or combined treatment strategies. We also cover the most recent developments in the field and outline the important areas of immune checkpoint molecules as prognostic variables and therapeutic targets in CCA.
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Affiliation(s)
- Fatemeh Vatankhah
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Salimi
- School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Amirreza Khalaji
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Sun Z, Sun X, Guo J, Li X, Wang Q, Su N, Chen M, Cao G, Yu Y, Wang M, Li H, Zhong H, Zou H, Ma K, Shen F, Zhang B, Sun X, Feng Y. Prognostic influence for hilar cholangiocarcinoma and comparisons of prognostic values of Mayo staging and TNM staging systems. Medicine (Baltimore) 2022; 101:e32250. [PMID: 36626512 PMCID: PMC9750704 DOI: 10.1097/md.0000000000032250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The study was designed to discuss the effect of stratification factors in the Mayo staging on the prognosis of hilar cholangiocarcinoma (HCCA) patients, and to evaluate the predictive value of the Mayo staging on the prognosis. The Kaplan-Meier survival curve and Log-rank test were used to perform univariate analysis on each index and obtain statistically significant influencing factors. The Kaplan-Meier survival curve and Log-rank test were used to analyze the correlation between the two staging systems and the survival period. The receiver operating characteristic (ROC) curves were used for each single staging system trend analysis, and comparison of their curve area to determine prognosis prediction ability for patients with HCCA. According to Kaplan-Meier survival curve changes and Log-rank test results, it was found that both staging systems were correlated with the survival time of the patients (P < .001). Through a pairwise comparison within the stages, it was found that the heterogeneity between the stages within the Mayo staging is very good, which was better than the TNM staging. A single trend analysis of the prognostic assessment capabilities of the two systems found that the area under the ROC curve of Mayo staging system (AUC = 0.587) was the largest and better than the TNM staging system (AUC = 0.501). Mayo staging can be used for preoperative patient prognosis assessment which can provide better stratification ability based on a single-center small sample study, and the predictive value is better than TNM staging.
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Affiliation(s)
- Zhaowei Sun
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- * Correspondence: Yujie Feng, Department of Hepatobiliary Surgery, Affliated Hospital of Qingdao University, Jiangsu 16, Qingdao 26000, China (e-mail: )
| | - Xiaozhi Sun
- Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jingyun Guo
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xueliang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qinlei Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Na Su
- Medical Imaging Department, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Menshou Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guanghua Cao
- Department of Hepatobiliary and Pancreatic Surgery, HuiKang Hospital of Qingdao, Shandong, China
| | - Yanan Yu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Maobing Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Haoran Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Haochen Zhong
- Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hao Zou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Kai Ma
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Fangzhen Shen
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bingyuan Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaozhi Sun
- Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yujie Feng
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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16
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Keulen AMV, Gaspersz MP, van Vugt JLA, Roos E, Olthof PB, Coelen RJS, Bruno MJ, van Driel LMJW, Voermans RP, van Eijck CHJ, van Hooft JE, van Lienden KP, de Jonge J, Polak WG, Poley JW, Pek CJ, Moelker A, Willemssen FEJA, van Gulik TM, Erdmann JI, Hol L, IJzermans JNM, Büttner S, Koerkamp BG. Success, complication, and mortality rates of initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma. Surgery 2022; 172:1606-1613. [PMID: 35989132 DOI: 10.1016/j.surg.2022.06.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/09/2022] [Accepted: 06/20/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND The patients with unresectable perihilar cholangiocarcinoma require biliary drainage to relieve symptoms and allow for palliative systemic chemotherapy. The aim of this study was to establish the success, complication, and mortality rates of the initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma at presentation. METHODS In this retrospective multicenter study, patients with unresectable perihilar cholangiocarcinoma who underwent initial endoscopic or percutaneous transhepatic biliary drainage between 2002 and 2014 were included. The success of drainage was defined as a successful biliary stent or drain placement, no unscheduled reintervention within 14 days, and serum bilirubin levels <50 μmol/L (ie, 2.9 mg/dL) or a >50% decrease in serum bilirubin after 14 days. Severe complications, and 90-day mortality were recorded. RESULTS Included were 186 patients: 161 (87%) underwent initial endoscopic biliary drainage and 25 (13%) underwent initial percutaneous transhepatic biliary drainage. The success of initial drainage was observed in 73 patients (45%) after endoscopic biliary drainage and 6 (24%) after percutaneous transhepatic biliary drainage. The reasons for an unsuccessful initial drainage were: the failure to place a drain or stent in 39 patients (21%), an unplanned reintervention within 14 days in 52 patients (28%), and the bilirubin level >50 μmol/L (or not halved) after 14 days of initial drainage in 16 patients (9%). Severe drainage-related complications occurred in 19 patients (12%) after endoscopic biliary drainage and in 3 (12%) after percutaneous transhepatic biliary drainage. Overall, 66 patients (36%) died within 90 days after initial biliary drainage. CONCLUSION Initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma had a success rate of 45% and a 90-day mortality rate of 36%. Future studies for patients with perihilar cholangiocarcinoma should focus on improving biliary drainage.
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Affiliation(s)
| | - Marcia P Gaspersz
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Eva Roos
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, the Netherlands
| | - Pim B Olthof
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Robert J S Coelen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, the Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Rogier P Voermans
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam Gastroenterology and Metabolism Institute, the Netherlands
| | | | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, the Netherlands
| | - Krijn P van Lienden
- Department of Radiology, Amsterdam University Medical Center, the Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Jan-Werner Poley
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Chulja J Pek
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - François E J A Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, the Netherlands
| | - Joris I Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, the Netherlands
| | - L Hol
- Department of Gastroenterology and Hepatology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Stefan Büttner
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
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17
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Liu P, Song Y, shakoor K, Peng C, Liu S. The pros and cons of the PCC staging system to guide surgical resectability and prognosis. J Cancer 2022; 13:3444-3451. [PMID: 36313036 PMCID: PMC9608210 DOI: 10.7150/jca.76696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/17/2022] [Indexed: 11/05/2022] Open
Abstract
Perihilar cholangiocarcinoma (PCC) is a malignant mass originating from the bile ducts. There is currently no unified treatment plan, and there are various treatment methods applied in clinical practice, as well as several different staging and typing systems to guide resectability, prognosis and survival prediction. The choice of treatment for PCC is closely related to the stage of the tumor. Accurate preoperative staging is necessary for correct resectability assessment and the selection of a reasonable treatment plan and surgical method; similarly, accurate postoperative pathological staging is necessary to guide further treatment and judgment of the patient's prognosis. A universally accepted staging system facilitates the comparison of cases between different centers, but there is much debate about the classification and staging of PCC. At present, the existing staging systems include the Bismuth-Corlette classification, AJCC/UICC TNM staging, modified T staging, Gazzaniga staging, JSBS staging, and Mayo staging. Each system has advantages, but there is no comprehensive guide for tumor resectability, prognosis, and survival. In this paper, the pros and cons of the different systems for staging PCC in terms of resectability, prognosis and survival prediction are discussed.
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Affiliation(s)
- Pei Liu
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University; Changsha 410005, China
| | - Yinghui Song
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University; Changsha 410005, China.,Central Laboratory of Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Kashif shakoor
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University; Changsha 410005, China
| | - Chuang Peng
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University; Changsha 410005, China.,✉ Corresponding authors: Chuang Peng MD PhD and Sulai Liu MD PhD; Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China. Tel/fax: 08673183929520. E-mail: and
| | - Sulai Liu
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University; Changsha 410005, China.,Central Laboratory of Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China.,✉ Corresponding authors: Chuang Peng MD PhD and Sulai Liu MD PhD; Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China. Tel/fax: 08673183929520. E-mail: and
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18
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Aphivatanasiri C, Sa-Ngiamwibool P, Sangkhamanon S, Intarawichian P, Kunprom W, Thanee M, Prajumwongs P, Khuntikeo N, Titapun A, Jareanrat A, Thanasukarn V, Srisuk T, Luvira V, Eurboonyanun K, Promsorn J, Loilome W, Wee A, Koonmee S. Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand. Front Med (Lausanne) 2022; 9:893252. [PMID: 36250068 PMCID: PMC9561347 DOI: 10.3389/fmed.2022.893252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
AimThis study aims to improve the classification performance of the eighth American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) by proposing the Khon Kaen University (KKU) staging system developed in cholangiocarcinoma-prevalent Northeast Thailand.MethodFour hundred eighty-eight patients with pCCA who underwent partial hepatectomy between 2002 and 2017 at the Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were included. Overall survival (OS) related to clinicopathological features was analyzed using the Kaplan–Meier method. Logrank test was performed in univariate analysis to compare OS data of clinicopathological features to determine risk factors for poor survival. Significant features were further analyzed by multivariate analysis (Cox regression) to identify prognostic factors which were then employed to modify the eighth AJCC staging system.ResultsMultivariate analysis showed that growth pattern (HR = 4.67–19.72, p < 0.001), moderately and poorly differentiated histological grades (HR = 2.31–4.99, p < 0.05 and 0.001, respectively), lymph node metastasis N1 and N2 (HR = 1.37 and 2.18, p < 0.05 and 0.01, respectively), and distant metastasis (HR = 2.11, p < 0.001) were independent factors when compared to their respective reference groups. There was a clear separation of patients with pCCA into KKU stage: I [OS = 116 months (mo.)], II (OS = 46 mo.), IIIA (OS = 24 mo.), IIIB (11 mo.), IVA (OS = 7 mo.), and IVB (OS = 6 mo.).ConclusionThe new staging system was based on the incorporation of growth patterns to modify the eighth AJCC staging system. The classification performance demonstrated that the KKU staging system was able to classify and distinctly separate patients with pCCA into those with good and poor outcomes. It was also able to improve the stratification performance and discriminative ability of different stages of pCCA classification better than the eighth AJCC staging system. Hence, the KKU staging system is proposed as an alternative model to augment the accuracy of survival prognostication and treatment performance for patients with pCCA.
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Affiliation(s)
- Chaiwat Aphivatanasiri
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Prakasit Sa-Ngiamwibool
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sakkarn Sangkhamanon
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piyapharom Intarawichian
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Waritta Kunprom
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Malinee Thanee
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piya Prajumwongs
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Narong Khuntikeo
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Attapol Titapun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Apiwat Jareanrat
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Vasin Thanasukarn
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Tharatip Srisuk
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Vor Luvira
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Kulyada Eurboonyanun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Julaluck Promsorn
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Watcharin Loilome
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Aileen Wee
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Supinda Koonmee
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- *Correspondence: Supinda Koonmee
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19
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Siriwong N, Sukaram T, Tansawat R, Apiparakoon T, Tiyarattanachai T, Marukatat S, Rerknimitr R, Chaiteerakij R. Exhaled volatile organic compounds for cholangiocarcinoma diagnosis. LIVER RESEARCH 2022; 6:191-197. [PMID: 39958199 PMCID: PMC11791817 DOI: 10.1016/j.livres.2022.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/14/2022] [Accepted: 09/01/2022] [Indexed: 02/16/2023]
Abstract
Objectives The difficulties in the early detection consequent to the lack of sensitive biomarkers render patients with cholangiocarcinoma (CCA) to have poor outcomes. Recently, sensitive and specific volatile organic compounds (VOCs) were identified in several cancers. However, the VOC profiles in CCA are not well-studied. Thus, we investigated the VOC profiles in exhaled breath of CCA patients and controls. Methods We prospectively collected exhaled breath samples from 30 consecutive patients newly diagnosed with CCA and 30 controls who did not have CCA (seven had benign biliary strictures and 23 had other medical conditions). Exhaled VOCs were identified using gas chromatography mass spectrometry Triple Quadrupoles system. Analysis of the significant differences in VOCs between cases and controls was conducted using supervised multivariate regression analysis. Further validation was performed for these VOCs in another cohort of 18 CCA patients and 22 controls. Results Levels of six compounds were significantly different between CCA patients and controls, namely, acetone, isopropyl alcohol, dimethyl sulfide, 1,4-pentadiene, allyl methyl sulfide, and N,N-dimethylacetamide. Acetone and dimethyl sulfide were independently associated with CCA as demonstrated in the multivariate analysis. Using the cut-off value of 8.59 × 107 arbitrary unit (AU), acetone had a sensitivity and specificity of 82.1% and 75.8%, respectively, with an area under the receiving operator curve (AUROC) of 0.85 for the CCA diagnosis. Acetone level was also significantly different between cases and controls in the validation cohort. Using the same cut-off value, the sensitivity, specificity, and AUROC was 59.1%, 66.7%, and 0.85, respectively. Conclusion Breath analysis may potentially be useful for CCA diagnosis. A cohort of patients with early-stage CCA in further studies is needed to confirm the ability of exhaled VOCs for the early detection of CCA.
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Affiliation(s)
- Nanicha Siriwong
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thanikan Sukaram
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Rossarin Tansawat
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Terapap Apiparakoon
- Department of Computer Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand
| | - Thodsawit Tiyarattanachai
- Clinical Sciences PhD International Program, Faculty of Medicine, Chulalongkorn University, Thailand
| | - Sanparith Marukatat
- Image Processing and Understanding Team, Artificial Intelligence Research Group, National Electronics and Computer Technology Center (NECTEC), Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand
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20
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Izquierdo-Sanchez L, Lamarca A, La Casta A, Buettner S, Utpatel K, Klümpen HJ, Adeva J, Vogel A, Lleo A, Fabris L, Ponz-Sarvise M, Brustia R, Cardinale V, Braconi C, Vidili G, Jamieson NB, Macias RI, Jonas JP, Marzioni M, Hołówko W, Folseraas T, Kupčinskas J, Sparchez Z, Krawczyk M, Krupa Ł, Scripcariu V, Grazi GL, Landa-Magdalena A, Ijzermans JN, Evert K, Erdmann JI, López-López F, Saborowski A, Scheiter A, Santos-Laso A, Carpino G, Andersen JB, Marin JJ, Alvaro D, Bujanda L, Forner A, Valle JW, Koerkamp BG, Banales JM. Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol 2022; 76:1109-1121. [PMID: 35167909 DOI: 10.1016/j.jhep.2021.12.010] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 11/17/2021] [Accepted: 12/06/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort. METHODS The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed. RESULTS Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors. CONCLUSION CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality. LAY SUMMARY This is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], perihilar [2C18], or distal [2C15] affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe.
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Affiliation(s)
- Laura Izquierdo-Sanchez
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Adelaida La Casta
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Stefan Buettner
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Kirsten Utpatel
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, the Netherlands
| | - Jorge Adeva
- Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Humanitas Clinical Research Center IRCSS, Humanitas University, Rozzano, Milan, Italy
| | - Luca Fabris
- Department of Molecular Medicine (DMM), University of Padua School of Medicine, Padua, Italy; Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA
| | - Mariano Ponz-Sarvise
- Clinica Universidad de Navarra and Program in Solid Tumors (CIMA), Universidad de Navarra, IDISNA, Pamplona, Spain
| | - Raffaele Brustia
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino "Sapienza" University of Rome, Latina, Italy
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, UK; The Royal Marsden NHS Trust, London & Surrey, UK
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Nigel B Jamieson
- Institute of Cancer Sciences, University of Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Rocio Ir Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, Biomedical Research Institute (IBSAL), Salamanca, Spain
| | - Jan Philipp Jonas
- University Hospital Zurich, Department of Visceral- and Transplant Surgery, Zurich, Switzerland; Clinic Favoriten, Department for Surgery, Wien, Austria
| | - Marco Marzioni
- Università Politecnica delle Marche, Department of Gastroenterology, Ancona, Italy
| | - Wacław Hołówko
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland
| | - Trine Folseraas
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Juozas Kupčinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Zeno Sparchez
- 3rd Medical Department, Institute for Gastroenterology and Hepatology, University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Marcin Krawczyk
- Department of Medicine II Saarland University Medical Center, Saarland University, Homburg, Germany; Laboratory of Metabolic Liver Diseases, Center for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Łukasz Krupa
- Department of Gastroenterology and Hepatology with Internal Disease Unit, Teaching Hospital No 1 in Rzeszów, Poland; Medical Department, University of Rzeszów, Poland
| | - Viorel Scripcariu
- Department of Morpho-Functional Sciences I, Department of Surgery II, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania
| | | | - Ana Landa-Magdalena
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Jan Nm Ijzermans
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Katja Evert
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Joris I Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Flora López-López
- Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | | | - Alvaro Santos-Laso
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Jesper B Andersen
- Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jose Jg Marin
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, Biomedical Research Institute (IBSAL), Salamanca, Spain
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain
| | - Alejandro Forner
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain; Liver Unit. Barcelona Clinic Liver Cancer (BCLC) group. Hospital Clinic Barcelona. IDIBAPS. University of Barcelona, Spain
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, "Instituto de Salud Carlos III" (ISCIII), Madrid, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
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21
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Current Perspectives on the Surgical Management of Perihilar Cholangiocarcinoma. Cancers (Basel) 2022; 14:cancers14092208. [PMID: 35565335 PMCID: PMC9104954 DOI: 10.3390/cancers14092208] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 04/21/2022] [Accepted: 04/21/2022] [Indexed: 02/08/2023] Open
Abstract
Cholangiocarcinoma (CCA) represents nearly 15% of all primary liver cancers and 2% of all cancer-related deaths worldwide. Perihilar cholangiocarcinoma (pCCA) accounts for 50-60% of all CCA. First described in 1965, pCCAs arise between the second-order bile ducts and the insertion of the cystic duct into the common bile duct. CCA typically has an insidious onset and commonly presents with advanced, unresectable disease. Complete surgical resection is technically challenging, as tumor proximity to the structures of the central liver often necessitates an extended hepatectomy to achieve negative margins. Intraoperative frozen section can aid in assuring negative margins and complete resection. Portal lymphadenectomy provides important prognostic and staging information. In specialized centers, vascular resection and reconstruction can be performed to achieve negative margins in appropriately selected patients. In addition, minimally invasive surgical techniques (e.g., robotic surgery) are safe, feasible, and provide equivalent short-term oncologic outcomes. Neoadjuvant chemoradiation therapy followed by liver transplantation provides a potentially curative option for patients with unresectable disease. New trials are needed to investigate novel chemotherapies, immunotherapies, and targeted therapies to better control systemic disease in the adjuvant setting and, potentially, downstage disease in the neoadjuvant setting.
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22
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Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma—A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14092079. [PMID: 35565209 PMCID: PMC9099890 DOI: 10.3390/cancers14092079] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/13/2022] [Accepted: 04/18/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary In patients with unresectable perihilar cholangiocarcinoma, adequate biliary drainage is essential. Stent patency remains a challenge in these complex patients, as both plastic and metal stent occlusion may occur, necessitating additional drainage procedures. Radiofrequency ablation (RFA) is a promising local treatment that has already proven its usefulness in other malignancies, such as hepatocellular carcinoma. In this meta-analysis and systematic review, we aimed to compare intraductal RFA with stent placement to stent placement alone in patients with unresectable perihilar cholangiocarcinoma. We found that RFA + stent treatment showed a significantly longer overall survival, in comparison to stent-only treatment. Further research is necessary in order to validate these findings to support the implementation of this promising strategy in clinical practice. Abstract Background: One of the cornerstones of palliative treatment for unresectable perihilar cholangiocarcinoma is biliary stent placement in order to restore biliary drainage. In this review, the potential added value of RFA with stent placement in comparison to stent placement alone in patients with unresectable perihilar cholangiocarcinoma is analyzed. Methods: We performed a comprehensive online search for relevant articles in November 2021 (PROSPERO ID: CRD42021288180). The primary endpoint was difference in overall survival. Secondary endpoints included overall survival, stent patency and complications. Only studies comparing survival after RFA + stent placement with stent placement alone were included in the meta-analysis. Non-comparative studies or comparative studies describing stent patency only were included in the systematic review. Results: A total of nine studies, including 217 patients with pCCA who underwent RFA + stent placement and 294 patients who underwent stent-only treatment, met the inclusion criteria for the primary endpoint analysis. Direct comparison between the two treatment groups showed a significantly longer overall survival for RFA + stent treatment, with a pooled HR of 0.65 [95% CI, 0.50–0.84, I2 = 38%]. When all eligible studies were included, RFA + stent treatment revealed an overall survival of 9.5 months [95% CI, 6.3–12.6], whereas survival for stent-only treatment was 7.0 months [95% CI, 5.7–8.2]. Due to the heterogeneity of the data, no pooled data analysis could be performed on stent patency or complications. Conclusions: RFA + stent placement displays promising potential to prolong survival. However, further research incorporating confounding factors like use of palliative chemotherapy is necessary in order to validate these findings.
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23
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Song J, Lei X, Lin H, Dai H, Liu X, Jiang Y, Hu F, Li Y, Fan H, Zhang L, Chen Z, Zhang C. Predictive model for the intraoperative unresectability of hilar cholangiocarcinoma: Reducing futile surgical exploration. PLoS One 2022; 17:e0258522. [PMID: 35417458 PMCID: PMC9007352 DOI: 10.1371/journal.pone.0258522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 09/29/2021] [Indexed: 12/25/2022] Open
Abstract
Introduction Surgical exploration is widely performed in hilar cholangiocarcinoma (HCCA), but the intraoperative resectability rate is only 60%-80%. Exploration substantially increases pain and mental stress, and the costs and length of hospital stay are considerably increased. Identifying preoperative risk factors associated with unresectability could decrease unnecessary exploration. Materials and methods In total, 440 HCCA patients from multiple centers were enrolled. Those receiving surgical exploration were divided into the resected and unresected groups. Morphological variables including Bismuth classification, lymph node metastasis and vessel invasion were obtained from radiological exams. Logistic regression for the training cohort was used to identify risk factors for unresectability, and a nomogram was constructed to calculate the unresectability rate. A calibration curve assessed the power of the nomogram. Results Among 311 patients receiving surgical exploration, 45 (14.7%) were unresectable by intraoperative judgment. Compared with the resected group, unresected patients had similar costs (p = 0.359) and lengths of hospital stay (p = 0.439). Multivariable logistic regression of the training cohort (235 patients) revealed that CA125, Bismuth-Corlette type IV, lymph node metastasis and hepatic artery invasion were risk factors for unresectability. Liver atrophy (p = 0.374) and portal vein invasion (p = 0.114) were not risk factors. The nomogram was constructed based on the risk factors. The concordance index (C-index) values of the calibration curve for predicting the unresectability rate of the training and validation (76 patients) cohorts were 0.900 (95% CI, 0.835–0.966) and 0.829 (95% CI, 0.546–0.902), respectively. Conclusion Analysis of preoperative factors could reveal intraoperative unresectability and reduce futile surgical explorations, ultimately benefiting HCCA patients.
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Affiliation(s)
- Jinglin Song
- Department of Public Economic System and Policy, School of Public Administration, Southwestern University of Finance and Economics, Chengdu, Sichuan, China
| | - Xiaofeng Lei
- Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong, China
| | - Heng Lin
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Haisu Dai
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xingchao Liu
- Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China
| | - Yan Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Hu
- College of Basic Medical Sciences, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yuancheng Li
- College of Basic Medical Sciences, Third Military Medical University (Army Medical University), Chongqing, China
| | - Haining Fan
- Qinghai University Affiliated Hospital, Xining, Qinghai, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zhiyu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- * E-mail: (CZ); (ZC)
| | - Chengcheng Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- * E-mail: (CZ); (ZC)
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Yu Z, Liu Q, Liao H, Shi J, Zhou Z, Yan Y, Xu J, He C, Mao K, Zhang J, Wang J, Xiao Z. Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study. J Gastrointest Oncol 2022; 13:833-846. [PMID: 35557567 PMCID: PMC9086037 DOI: 10.21037/jgo-21-543] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 12/28/2021] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. METHODS A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. RESULTS The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. CONCLUSIONS The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.
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Affiliation(s)
- Zhimin Yu
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qinghua Liu
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hao Liao
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Juanyi Shi
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenyu Zhou
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongcong Yan
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junyao Xu
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chuanchao He
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Kai Mao
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jianlong Zhang
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Wang
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiyu Xiao
- Guandong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of hepatobiliary surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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van Keulen A, Franssen S, van der Geest LG, de Boer MT, Coenraad M, van Driel LMJW, Erdmann JI, Haj Mohammad N, Heij L, Klümpen H, Tjwa E, Valkenburg‐van Iersel L, Verheij J, Groot Koerkamp B, Olthof PB, the Dutch Hepatocellular & Cholangiocarcinoma Group (DHCG). Nationwide treatment and outcomes of perihilar cholangiocarcinoma. Liver Int 2021; 41:1945-1953. [PMID: 33641214 PMCID: PMC8359996 DOI: 10.1111/liv.14856] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 02/06/2021] [Accepted: 02/17/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed to analyse the outcomes of patients with pCCA in a nationwide cohort. METHODS Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival. RESULTS A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7-5.7) months. Three-hundred-ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti-cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2-34.0), 12.2 (95% CI 11.0-13.3), 14.5 (95%CI 8.2-20.8) and 2.9 (95% CI 2.6-3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non-academic and 32% in academic centres (P < .001), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7-11.7) months in academic centres compared to 4.9 (95% CI 4.3-5.4) months in non-academic centres (P < .001). CONCLUSIONS In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population-based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients.
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Affiliation(s)
- Anne‐Marleen van Keulen
- Department of SurgeryErasmus MC Cancer InstituteRotterdamthe Netherlands
- Department of SurgeryReinier de Graaf GasthuisDelftthe Netherlands
| | - Stijn Franssen
- Department of SurgeryErasmus MC Cancer InstituteRotterdamthe Netherlands
| | - Lydia G. van der Geest
- Department of ResearchNetherlands Comprehensive Cancer Organization (IKNL)Utrechtthe Netherlands
| | - Marieke T. de Boer
- Department of SurgeryUniversity Medical Center GroningenGroningenthe Netherlands
| | - Minneke Coenraad
- Department of Gastroenterology and HepatologyLeiden University Medical CenterLeidenthe Netherlands
| | | | - Joris I. Erdmann
- Department of SurgeryAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamthe Netherlands
| | - Nadia Haj Mohammad
- Department of Medical OncologyUniversity Medical Center Utrecht/ Regional Academic Cancer Center UtrechtUtrecht UniversityUtrechtthe Netherlands
| | - Lara Heij
- Institute of PathologyUniversity Hospital RWTH AachenAachenGermany
- Visceral and Transplant SurgeryUniversity Hospital RWTH AachenAachenGermany
- NUTRIM School of Nutrition and Translational Research in MetabolismMaastricht UniversityMaastrichtthe Netherlands
| | - Heinz‐Josef Klümpen
- Department of Medical OncologyAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamthe Netherlands
| | - Eric Tjwa
- Department of GastroenterologyRadboud University Medical CenterNijmegenthe Netherlands
| | - Liselot Valkenburg‐van Iersel
- Department of Internal MedicineDivision of Medical OncologyGROW‐School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastrichtthe Netherlands
| | - Joanne Verheij
- Department of PathologyAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamthe Netherlands
| | - Bas Groot Koerkamp
- Department of SurgeryErasmus MC Cancer InstituteRotterdamthe Netherlands
| | - Pim B. Olthof
- Department of SurgeryErasmus MC Cancer InstituteRotterdamthe Netherlands
- Department of SurgeryAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamthe Netherlands
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26
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Strainiene S, Sedleckaite K, Jarasunas J, Savlan I, Stanaitis J, Stundiene I, Strainys T, Liakina V, Valantinas J. Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review. World J Clin Cases 2021; 9:6155-6169. [PMID: 34368338 PMCID: PMC8316968 DOI: 10.12998/wjcc.v9.i21.6155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/30/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience. CASE SUMMARY A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo. CONCLUSION IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.
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Affiliation(s)
- Sandra Strainiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | | | - Juozas Jarasunas
- Department of Radiology, Nuclear Medicine and Medical Physics, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ilona Savlan
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Juozas Stanaitis
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ieva Stundiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Tomas Strainys
- Clinic of Anesthesiology and Intensive Care Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Valentina Liakina
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Science, Vilnius Gediminas Technical University, Vilnius 10223, Lithuania
| | - Jonas Valantinas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
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Liang XY, Li W, Liu F, Kang XD. A Retrospective Study of Biliary Drainage Strategies for Patients with Malignant Hilar Biliary Strictures. Cancer Manag Res 2021; 13:4767-4776. [PMID: 34168496 PMCID: PMC8216661 DOI: 10.2147/cmar.s308833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/24/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The main aim of this study was to compare the efficacy and safety of different biliary drainage strategies, including percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary stenting (EBS) and unilateral versus bilateral stenting, in patients with unresectable malignant hilar biliary strictures (MHBSs). PATIENTS AND METHODS This was a retrospective review of patients with inoperable MHBSs who underwent biliary drainage by either EBS or PTBD. Efficacy and safety were compared between the two pathways and between unilateral and bilateral stenting in the EBS group. The survival duration was analyzed with K-M curves and Log rank tests. RESULTS From January 2015 to December 2019, a total of 206 (126: EBS and 80: PTBD) patients with MHBSs were enrolled in our study and underwent 270 procedures (173: EBS and 97: PTBD). Bilateral stenting was superior to unilateral stenting in terms of clinical success (69.6% vs 50.6%, p=0.039), especially for patients with Bismuth type IV (70.0% vs 30.3%, p=0.002). A higher decrease in bilirubin was seen with PTBD in patients with Bismuth types III-IV (66.9 vs 36.7, p=0.006). A survival advantage was seen in successful drainage (227 days vs 82 days, p<0.001), lower tumor-node-metastasis (TNM) scores (I-II) (195 days vs 139 days, p=0.012), and cholangiocarcinoma (184 days vs 84 days, p=0.001). CONCLUSION For patients with advanced MHBSs, bilateral stenting may achieve a better drainage effect than unilateral stenting, and PTBD may have a better performance in relieving cholestasis than EBS. Successful drainage and cholangiocarcinoma may provide greater long-term survival benefits.
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Affiliation(s)
- Xin-Yue Liang
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, People’s Republic of China
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Wen Li
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, People’s Republic of China
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Fang Liu
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, People’s Republic of China
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Xin-Dan Kang
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, People’s Republic of China
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Qin H, Hu X, Zhang J, Dai H, He Y, Zhao Z, Yang J, Xu Z, Hu X, Chen Z. Machine-learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection. Liver Int 2021; 41:837-850. [PMID: 33306240 DOI: 10.1111/liv.14763] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 11/11/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Up to 40%-65% of patients with perihilar cholangiocarcinoma (PHC) rapidly progress to early recurrence (ER) even after curative resection. Quantification of ER risk is difficult and a reliable prognostic prediction tool is absent. We developed and validated a multilevel model, integrating clinicopathology, molecular pathology and radiology, especially radiomics coupled with machine-learning algorithms, to predict the ER of patients after curative resection in PHC. METHODS In total, 274 patients who underwent contrast-enhanced CT (CECT) and curative resection at 2 institutions were retrospectively identified and randomly divided into training (n = 167), internal validation (n = 70) and external validation (n = 37) sets. A machine-learning analysis of 18,120 radiomic features based on multiphase CECT and 48 clinico-radiologic characteristics was performed for the multilevel model. RESULTS Comprehensively, 7 independent factors (tumour differentiation, lymph node metastasis, pre-operative CA19-9 level, enhancement pattern, A-Shrink score, V-Shrink score and P-Shrink score) were built to the multilevel model and quantified the risk of ER. We benchmarked the gain in discrimination with the area under the curve (AUC) of 0.883, superior to the rival clinical and radiomic models (AUCs 0.792-0.805). The accuracy (ACC) of the multilevel model was 0.826, which was significantly higher than those of the conventional staging systems (AJCC 8th (0.641), MSKCC (0.617) and Gazzaniga (0.581)). CONCLUSION The radiomics-based multilevel model demonstrated superior performance to rival models and conventional staging systems, and could serve as a visual prognostic tool to plan surveillance of ER and guide post-operative individualized management in PHC.
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Affiliation(s)
- Huan Qin
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xianling Hu
- Communication NCO Academy, Army Engineering University of PLA, Chongqing, China
| | - Junfeng Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
| | - Haisu Dai
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yonggang He
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiping Zhao
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiali Yang
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhengrong Xu
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xiaofei Hu
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiyu Chen
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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Lee JW, Lee JH, Park Y, Kwon J, Lee W, Song KB, Hwang DW, Kim SC. Prognostic Impact of Perioperative CA19-9 Levels in Patients with Resected Perihilar Cholangiocarcinoma. J Clin Med 2021; 10:1345. [PMID: 33805079 PMCID: PMC8036534 DOI: 10.3390/jcm10071345] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/08/2021] [Accepted: 03/22/2021] [Indexed: 01/03/2023] Open
Abstract
We aimed to examine the predictive value of changes in perioperative carbohydrate antigen (CA) 19-9 levels for patients operated for perihilar cholangiocarcinoma (pCCA). A total of 322 patients who underwent curative resection for pCCA were divided into three groups: normal preoperative CA19-9 (CA19-9 ≤ 37 U/mL), normalization (preoperative CA19-9 > 37 U/mL, postoperative CA19-9 ≤ 37 U/mL), and non-normalization (pre- and postoperative CA19-9 > 37 U/mL) groups. The association of clinicopathological factors with overall survival (OS) was investigated. The non-normalization group (n = 82) demonstrated significantly worse OS than the normal CA19-9 (n = 114) and normalization (n = 126) groups (5-year OS, 16.9%, 29.4%, and 34.4%, respectively; both p ≤ 0.001). The cutoff points of 300 U/mL for preoperative (p = 0.001) and 37 U/mL for postoperative (p < 0.001) CA19-9 levels showed the strongest prognostic values. In the non-normalization group, patients who underwent R1 resection displayed significantly worse OS than those who underwent R0 resection (median OS, 10.2 vs. 15.7 months; p = 0.016). Multivariate analysis revealed that lymph node metastasis (hazard ratio (HR), 2.07; p < 0.001), postoperative CA19-9 > 37 U/mL (HR, 1.94; p < 0.001), transfusion (HR, 1.74; p = 0.002), and T stage (T3,4) (HR, 1.67; p = 0.006) were related to worse OS. Persistent high CA19-9 level after resection of pCCA and R1 resection, especially in the non-normalization group, was associated with poor OS. A high postoperative CA19-9 level was an independent prognostic factor in resected pCCA.
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Affiliation(s)
- Jong Woo Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Anyang 14068, Korea;
| | - Jae Hoon Lee
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Yejong Park
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Jaewoo Kwon
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Woohyung Lee
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Ki Byung Song
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Dae Wook Hwang
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
| | - Song Cheol Kim
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (Y.P.); (J.K.); (W.L.); (K.B.S.); (D.W.H.); (S.C.K.)
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30
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Nooijen LE, Swijnenburg RJ, Klümpen HJ, Verheij J, Kazemier G, van Gulik TM, Erdmann JI. Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art. Visc Med 2021; 37:18-25. [PMID: 33708815 PMCID: PMC7923954 DOI: 10.1159/000514032] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 12/23/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Surgical therapy still offers the only chance of long-term survival for patients with perihilar cholangiocarcinoma (pCCA). The aim of this narrative review is to summarize the current standards and challenges in the surgical treatment of pCCA. SUMMARY After imaging and defining resectability, the first step towards optimal surgical treatment is optimizing biliary drainage and preventing cholangitis, followed by securing adequate future liver remnant volume and/or function. The main goal of resection for pCCA is achieving radical resection and ultimately long-term survival. In order to achieve radical resection, several points will be addressed (e.g., vascular resection and reconstruction, intraoperative frozen sections, right versus left hemihepatectomy, and the usefulness of preoperative [chemo]therapy). KEY MESSAGES In order to optimize long-term outcomes for patients with pCCA, collaboration between leading centers should be increased. In addition, this collaboration is necessary to design large prospective randomized controlled trials, as the incidence of pCCA is low and the number of resectable patients is even lower. Currently, most results are based on small retrospective cohort studies resulting in low evidence. In order to properly investigate how to improve long-term survival, we need to set up trials to confirm the results of small series suggesting the positive effect of preoperative chemotherapy and extended lymph node resection.
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Affiliation(s)
- Lynn E. Nooijen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Thomas M. van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joris I. Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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31
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Ren A, Li Z, Zhang X, Deng R, Ma Y. A model for predicting post-liver transplantation recurrence in intrahepatic cholangiocarcinoma recipients. J Gastrointest Oncol 2021; 11:1283-1290. [PMID: 33457001 DOI: 10.21037/jgo-20-209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background It is important to select appropriate patients for improving the outcomes of liver transplantation for intrahepatic cholangiocarcinoma (iCCA). The objective of this study was to establish a predictive model for the recurrence of iCCA after liver transplantation. Methods Twenty-one patients who received liver transplantation for iCCA were used to construct a model for predicting recurrence. Predictors of recurrence were tested by a Cox model analysis. The results were validated in 28 patients who were followed up. Results Diameter and number of tumors, and CA19-9 level independently predicted tumor recurrence. At a Cox score threshold of 0.736 [95% confidence interval (CI): 0.549-0.923], a model combining these factors was highly predictive of tumor recurrence and death. A simplified version of the model identified a cut-off value of 6. The 5-year OS rate was lower in patients with a score >6 points compared to those with a score ≤6 points (P=0.005). The 5-year recurrence rate was higher in patients with a score >6 points as compared to those with a score ≤6 points (P=0.034). Conclusions The model developed was useful for predicting recurrence of iCCA after liver transplantation. Large sample, multicenter studies are needed to validate the findings.
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Affiliation(s)
- Ao Ren
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhongqiu Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xuzhi Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ronghai Deng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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32
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Italian Clinical Practice Guidelines on Cholangiocarcinoma - Part I: Classification, diagnosis and staging. Dig Liver Dis 2020; 52:1282-1293. [PMID: 32893173 DOI: 10.1016/j.dld.2020.06.045] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 12/11/2022]
Abstract
Cholangiocarcinoma (CCA) is the second most common primary liver cancer, characterized by a poor prognosis and resistance to chemotherapeutics. The progressive increase in CCA incidence and mortality registered worldwide in the last two decades and the need to clarify various aspects of clinical management have prompted the Italian Association for the Study of the Liver (AISF) to commission the drafting of dedicated guidelines in collaboration with a group of Italian scientific societies. These guidelines have been formulated in accordance with the Italian National Institute of Health indications and developed by following the GRADE method and related advancements.
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33
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Zhang Y, Wu Z, Wang X, Li C, Chang J, Jiang W, Wang H, Wang Y, Li X. Development and external validation of a nomogram for predicting the effect of tumor size on survival of patients with perihilar cholangiocarcinoma. BMC Cancer 2020; 20:1044. [PMID: 33126868 PMCID: PMC7596930 DOI: 10.1186/s12885-020-07501-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 10/06/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The effect of tumor size on account of long-term survival results in perihilar cholangiocarcinoma (PCCA) patients has remained a controversial debate. It is urgent necessary to identify the optimal cutoff value of tumor size in PCCA and integrate tumor size with other prognostic factors into a nomogram to improve the predictive accuracy of prognosis of patients with PCCA. METHODS Three hundred sixty-three PCCA patients underwent surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database. X-tile program was used to identify the optimal cutoff value of tumor size. A nomogram including tumor size was established to predict 1-, 3- and 5-year cancer-specific survival (CSS) based on the independent risk factors chosen by Kaplan-Meier methods and multivariable cox regression models. The precision of the nomogram for predicting survival was validated internally and externally. RESULTS PCCA patients underwent surgical resection were classified into 1-19 mm, 20-33 mm and ≥ 34 mm subgroups based on the optimal cutoff for tumor size in terms of CSS. And we noticed that more larger tumor size group had worse tumor grade, advanced T stage, more positive regional lymph nodes and more frequent vascular invasion. The nomogram according to the independent factors was well calibrated and displayed better discrimination power than 7th Tumor-Node-Metastasis (TNM) stage systems. CONCLUSIONS The results demonstrated that the larger tumor size of PCCA was, the worse survival would be. The proposed nomogram, which outperforms the conventional TNM staging system, showed relatively good performance and could be considered as convenient individualized predictive tool for prognosis of PCCA patients.
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Affiliation(s)
- Yaodong Zhang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Zhengshan Wu
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Xing Wang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
- Department of Hepatobiliary and Laparoscopic Surgery, Yixing People's Hospital, Yixing, Jiangsu Province, China
| | - Changxian Li
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Jiang Chang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Wangjie Jiang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Hongwei Wang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Yirui Wang
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China
| | - Xiangcheng Li
- Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.
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34
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Zhang JX, Ding Y, Yan HT, Zhou CG, Liu J, Liu S, Zu QQ, Shi HB. Skeletal-muscle index predicts survival after percutaneous transhepatic biliary drainage for obstructive jaundice due to perihilar cholangiocarcinoma. Surg Endosc 2020; 35:6073-6080. [PMID: 33090316 DOI: 10.1007/s00464-020-08099-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 10/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Sarcopenia is emerging as a prognostic factor in patients with malignant diseases. The prognostication of perihilar cholangiocarcinoma (PHC) with obstructive jaundice was complex, because these patients suffered compete mortality events beyond cancer itself. Our study was to investigate the association between low skeletal-muscle index and overall survival (OS) after percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice due to PHC. METHODS We performed a retrospective survival analysis of patients undergoing PTBD for PHC-related obstructive jaundice between January 2016 and March 2019. Using computed tomography, we measured skeletal-muscle mass at the third lumbar vertebra (L3) to obtain a skeletal-muscle index (SMI). Then, we compared OS between low- and high-SMI groups. Furthermore, factors that could potentially affect OS were assessed. RESULTS One hundred and four patients (56 males; mean age 66 ± 12 years) were analyzed. Median OS after PTBD was 150 days. OS was shorter in patients with low SMI than in those with high SMI (median OS, 120 vs. 270 days; P < 0.001). Multivariate analysis indicated that low SMI (hazard ratio [HR] 3.46; 95% confidence interval [CI] 1.14-5.60; P < 0.001), intrahepatic metastasis (HR 2.98; 95% CI 1.89-4.69; P < 0.001) and elevated carbohydrate antigen (CA) 19-9 level (HR 1.00; 95% CI 1.00-1.00; P = 0.04) were significantly associated with OS. CONCLUSION Low SMI was a predictor of dismal OS after PTBD for patients with PHC-related obstructive jaundice.
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Affiliation(s)
- Jin-Xing Zhang
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China
| | - Ye Ding
- Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Hai-Tao Yan
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China
| | - Chun-Gao Zhou
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China
| | - Jin Liu
- Department of Clinical Medicine Research Institution, The First Affiliated Hospital With Nanjing Medical University, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China
| | - Qing-Quan Zu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
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Belkouz A, Nooijen LE, Riady H, Franken LC, van Oijen MGH, Punt CJA, Erdmann JI, Klümpen HJ. Efficacy and safety of systemic induction therapy in initially unresectable locally advanced intrahepatic and perihilar cholangiocarcinoma: A systematic review. Cancer Treat Rev 2020; 91:102110. [PMID: 33075684 DOI: 10.1016/j.ctrv.2020.102110] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 09/23/2020] [Accepted: 09/25/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND According to international guidelines, induction therapy may be considered in selected patients with initially unresectable locally advanced cholangiocarcinoma. The criteria for (un)resectability in cholangiocarcinoma varies between studies and no consensus-based agreement is available about these criteria. By performing a systematic literature review, we aimed to investigate the efficacy and safety of systemic induction therapy in initially unresectable locally advanced perihilar (pCCA) and intrahepatic cholangiocarcinoma (iCCA) and summarize resectability criteria used across studies. METHODS A literature search was performed in PubMed, EMBASE, Web of Science and Cochrane library to identify studies on systemic induction therapy in locally advanced pCCA and/or iCCA. The primary outcome was resection rate (RR) after induction therapy and secondary outcomes were overall survival (OS) and objective response rate (ORR). RESULTS Ten studies with a total of 1167 patients met the inclusion criteria and were included in this review. Among these patients, 334 (28.6%) were treated with systemic induction therapy. Across the studies, different types of chemotherapy regimens were administered (e.g., gemcitabine (based) chemotherapy and 5-FU (based) chemotherapy). Only six studies provided sufficient data and were used to analyze pooled (radical) resection rates. After induction therapy, 94 patients (39.2%) underwent a resection, of which R0 resections (22.9%). Pooled data on OS showed, better OS for chemotherapy plus resection versus chemotherapy only (pooled HR = 0.31, 95% CI = 0.19-0.50; P value < 0.0001). CONCLUSION Adequately selected patients with locally advanced pCCA or iCCA may benefit from induction therapy followed by surgical resection. Prospective randomized controlled trials are warranted.
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Affiliation(s)
- Ali Belkouz
- Amsterdam UMC, Dept. of Medical Oncology, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Lynn E Nooijen
- Amsterdam UMC, Dept. of Surgery, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Hanae Riady
- VU Amsterdam, Faculty of Biomedical Sciences, Amsterdam, the Netherlands
| | - Lotte C Franken
- Amsterdam UMC, Dept. of Surgery, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Martijn G H van Oijen
- Amsterdam UMC, Dept. of Medical Oncology, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Cornelis J A Punt
- Amsterdam UMC, Dept. of Medical Oncology, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Joris I Erdmann
- Amsterdam UMC, Dept. of Surgery, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Heinz-Josef Klümpen
- Amsterdam UMC, Dept. of Medical Oncology, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
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Vugts JJA, Gaspersz MP, Roos E, Franken LC, Olthof PB, Coelen RJS, van Vugt JLA, Labeur TA, Brouwer L, Besselink MGH, IJzermans JNM, Darwish Murad S, van Gulik TM, de Jonge J, Polak WG, Busch ORC, Erdmann JL, Groot Koerkamp B, Buettner S. Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma. Ann Surg Oncol 2020; 28:1483-1492. [PMID: 32901308 PMCID: PMC7892510 DOI: 10.1245/s10434-020-09001-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/22/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers. METHODS Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT. RESULTS A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3-23). CONCLUSION Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.
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Affiliation(s)
- Jaynee J A Vugts
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Eva Roos
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lotte C Franken
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Pim B Olthof
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Tim A Labeur
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lieke Brouwer
- Department of Gastroenterology, Maasstad Ziekenhuis, Rotterdam, The Netherlands
| | - Marc G H Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joris L Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, Calvisi DF, Perugorria MJ, Fabris L, Boulter L, Macias RIR, Gaudio E, Alvaro D, Gradilone SA, Strazzabosco M, Marzioni M, Coulouarn C, Fouassier L, Raggi C, Invernizzi P, Mertens JC, Moncsek A, Ilyas SI, Heimbach J, Koerkamp BG, Bruix J, Forner A, Bridgewater J, Valle JW, Gores GJ. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 2020; 17:557-588. [PMID: 32606456 PMCID: PMC7447603 DOI: 10.1038/s41575-020-0310-z] [Citation(s) in RCA: 1459] [Impact Index Per Article: 291.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/29/2020] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
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Affiliation(s)
- Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain.
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
| | - Jose J G Marin
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Shahid A Khan
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy
| | - Jesper B Andersen
- Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Chiara Braconi
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Diego F Calvisi
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
| | - Luca Fabris
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy
- Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA
| | - Luke Boulter
- MRC-Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Rocio I R Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca, Spain
| | - Eugenio Gaudio
- Division of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Domenico Alvaro
- Department of Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | | | - Mario Strazzabosco
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy
- Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA
| | - Marco Marzioni
- Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy
| | | | - Laura Fouassier
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France
| | - Chiara Raggi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center of Autoimmune Liver Diseases, Department of Medicine and Surgery, San Gerardo Hospital, University of Milano, Bicocca, Italy
| | - Joachim C Mertens
- Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zürich, Switzerland
| | - Anja Moncsek
- Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zürich, Switzerland
| | - Sumera I. Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | | | | | - Jordi Bruix
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Alejandro Forner
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), San Sebastian, Spain
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - John Bridgewater
- Department of Medical Oncology, UCL Cancer Institute, London, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
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Shi XQ, Zhang JY, Tian H, Tang LN, Li AL. Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis. J Zhejiang Univ Sci B 2020; 21:549-559. [PMID: 32633109 DOI: 10.1631/jzus.b1900691] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. METHODS We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. RESULTS Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002). CONCLUSIONS A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.
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Affiliation(s)
- Xin-Qi Shi
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Jing-Yu Zhang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Hua Tian
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ling-Na Tang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ai-Lin Li
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
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Gaspersz MP, Buettner S, van Vugt JLA, de Jonge J, Polak WG, Doukas M, Ijzermans JNM, Koerkamp BG, Willemssen FEJA. Evaluation of the New American Joint Committee on Cancer Staging Manual 8th Edition for Perihilar Cholangiocarcinoma. J Gastrointest Surg 2020; 24:1612-1618. [PMID: 30756314 PMCID: PMC7359130 DOI: 10.1007/s11605-019-04127-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 01/16/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND The aim was to compare the prognostic accuracy of cross-sectional imaging of the 7th and 8th editions of the American Joint Committee on Cancer(AJCC) staging system for perihilar cholangiocarcinoma(PHC). METHODS All patients with PHC between 2002 and 2014 were included. Imaging at the time of presentation was reassessed and clinical tumor-node-metastasis (cTNM) stage was determined according to the 7th and 8th editions of the AJCC staging system. Comparison of the prognostic accuracy was performed using the concordance index (c-index). RESULTS A total of 248 PHC patients were included;45 patients(18.1%) underwent a curative-intent resection, whereas 203 patients(81.9%) did not because they were unfit for surgery or were diagnosed with locally advanced or metastatic disease during workup. Prognostic accuracy was comparable between the 7th and 8th editions (c-index 0.57 vs 0.58). For patients who underwent a curative-intent resection, the prognostic accuracy of the 8th edition (0.67) was higher than the 7th (0.65). For patients who did not undergo a curative-intent resection, the prognostic accuracy was poor in both the 7th as the 8th editions (0.54 vs 0.57). CONCLUSION The 7th and 8th editions of the AJCC staging system for PHC have comparable prognostic accuracy. Prognostic accuracy was particularly poor in unresectable patients.
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Affiliation(s)
- Marcia P. Gaspersz
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Jeroen L. A. van Vugt
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Wojciech G. Polak
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan N. M. Ijzermans
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
| | - François E. J. A. Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
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Cillo U, Fondevila C, Donadon M, Gringeri E, Mocchegiani F, Schlitt HJ, Ijzermans JNM, Vivarelli M, Zieniewicz K, Olde Damink SWM, Groot Koerkamp B. Surgery for cholangiocarcinoma. Liver Int 2019; 39 Suppl 1:143-155. [PMID: 30843343 PMCID: PMC6563077 DOI: 10.1111/liv.14089] [Citation(s) in RCA: 219] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/22/2019] [Accepted: 02/27/2019] [Indexed: 12/13/2022]
Abstract
Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5-year overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post-operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection.
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Affiliation(s)
- Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation UnitPadova University HospitalPadovaItaly
| | - Constantino Fondevila
- Department of General & Digestive Surgery, Institut de Malalties Digestives I Metabòliques (IMDiM)Hospital Clínic, University of BarcelonaSpain
| | - Matteo Donadon
- Department of Surgery, Division of Hepatobiliary and General SurgeryHumanitas Clinical and Research Center, Humanitas UniversityRozzanoItaly
| | - Enrico Gringeri
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation UnitPadova University HospitalPadovaItaly
| | - Federico Mocchegiani
- Hepatopancreatobiliary and Transplant Unit, Department of Experimental and Clinical MedicinePolytechnic University of MarcheAnconaItaly
| | - Hans J. Schlitt
- Department of SurgeryUniversity Hospital RegensburgRegensburgGermany
| | - Jan N. M. Ijzermans
- Department of SurgeryErasmus MC, University Medical Center RotterdamRotterdamThe Netherlands
| | - Marco Vivarelli
- Hepatopancreatobiliary and Transplant Unit, Department of Experimental and Clinical MedicinePolytechnic University of MarcheAnconaItaly
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver SurgeryMedical University of WarsawWarsawPoland
| | - Steven W. M. Olde Damink
- Department of SurgeryMaastricht University Medical CenterMaastrichtThe Netherlands
- Department of General, Visceral and Transplantation SurgeryRWTH University Hospital AachenAachenGermany
| | - Bas Groot Koerkamp
- Department of SurgeryErasmus MC, University Medical Center RotterdamRotterdamThe Netherlands
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Fabris L, Perugorria MJ, Mertens J, Björkström NK, Cramer T, Lleo A, Solinas A, Sänger H, Lukacs-Kornek V, Moncsek A, Siebenhüner A, Strazzabosco M. The tumour microenvironment and immune milieu of cholangiocarcinoma. Liver Int 2019; 39 Suppl 1:63-78. [PMID: 30907492 PMCID: PMC10878127 DOI: 10.1111/liv.14098] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 02/25/2019] [Accepted: 02/27/2019] [Indexed: 12/11/2022]
Abstract
Tumour microenvironment is a complex, multicellular functional compartment that, particularly when assembled as an abundant desmoplastic reaction, may profoundly affect the proliferative and invasive abilities of epithelial cancer cells. Tumour microenvironment comprises not only stromal cells, mainly cancer-associated fibroblasts, but also immune cells of both the innate and adaptive system (tumour-associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes), and endothelial cells. This results in an intricate web of mutual communications regulated by an extensively remodelled extracellular matrix, where the tumour cells are centrally engaged. In this regard, cholangiocarcinoma, in particular the intrahepatic variant, has become the focus of mounting interest in the last years, largely because of the lack of effective therapies despite its rising incidence and high mortality rates worldwide. On the other hand, recent studies in pancreatic cancer, which similarly to cholangiocarcinoma, is highly desmoplastic, have argued against a tumour-promoting function of the tumour microenvironment. In this review, we will discuss recent developments concerning the role of each cellular population and their multifaceted interplay with the malignant biliary epithelial counterpart. We ultimately hope to provide the working knowledge on how their manipulation may lead to a therapeutic gain in cholangiocarcinoma.
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Affiliation(s)
- Luca Fabris
- Department of Molecular Medicine, University of Padua, Padova, Italy
- Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA
| | - María Jesús Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastián, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Instituto de Salud Carlos III), Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Joachim Mertens
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Niklas K. Björkström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Thorsten Cramer
- Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, Aachen, Germany
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
- ESCAM – European Surgery Center Aachen Maastricht, Germany and The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
| | - Antonio Solinas
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Hanna Sänger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital, Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Veronika Lukacs-Kornek
- Institute of Experimental Immunology, University Hospital, Friedrich-Wilhelms-Universität Bonn, Germany
| | - Anja Moncsek
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Alexander Siebenhüner
- Department of Hematology and Medical Oncology, University Hospital Zürich, Zürich, Switzerland
| | - Mario Strazzabosco
- Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA
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van Vugt JL, Gaspersz MP, Vugts J, Buettner S, Levolger S, de Bruin RW, Polak WG, de Jonge J, Willemssen FE, Groot Koerkamp B, IJzermans JN. Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment. Dig Surg 2019; 36:144-152. [PMID: 29455204 PMCID: PMC6482985 DOI: 10.1159/000486867] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 01/16/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. METHODS Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. RESULTS Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. CONCLUSION A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.
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Affiliation(s)
- Jeroen L.A. van Vugt
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands,*Jeroen L.A. van Vugt, MD, Department of Surgery, Erasmus MC University Medical Center, Wytemaweg 80, NL–3015 CE, Rotterdam (The Netherlands), E-Mail
| | - Marcia P. Gaspersz
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Jaynee Vugts
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Stef Levolger
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Ron W.F. de Bruin
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Wojciech G. Polak
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - François E.J.A. Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Jan N.M. IJzermans
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
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Gaspersz MP, Buettner S, Roos E, van Vugt JLA, Coelen RJS, Vugts J, Wiggers JK, Allen PJ, Besselink MG, Busch ORC, Belt EJ, D'Angelica MI, DeMatteo RP, de Jonge J, Kingham TP, Polak WG, Willemssen FEJA, van Gulik TM, Jarnagin WR, Ijzermans JNM, Groot Koerkamp B. A preoperative prognostic model to predict surgical success in patients with perihilar cholangiocarcinoma. J Surg Oncol 2018; 118:469-476. [PMID: 30132904 DOI: 10.1002/jso.25174] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 06/27/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. STUDY DESIGN Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. RESULTS In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). CONCLUSION Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.
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Affiliation(s)
- Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Eva Roos
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jaynee Vugts
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jimme K Wiggers
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Eric J Belt
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | | | - Ronald P DeMatteo
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - T Peter Kingham
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - François E J A Willemssen
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - William R Jarnagin
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Jan N M Ijzermans
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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Wiggers JK, Groot Koerkamp B, van Klaveren D, Coelen RJ, Nio CY, Allen PJ, Besselink MG, Busch OR, D'Angelica MI, DeMatteo RP, Kingham TP, van Gulik TM, Jarnagin WR. Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging. J Am Coll Surg 2018; 227:238-246.e2. [PMID: 29627334 PMCID: PMC6089225 DOI: 10.1016/j.jamcollsurg.2018.03.041] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 03/20/2018] [Accepted: 03/21/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Many patients with resectable perihilar cholangiocarcinoma (PHC) on imaging are diagnosed intraoperatively with occult metastatic or locally advanced disease, precluding a curative-intent resection. This study aimed to develop and validate a preoperative risk score. STUDY DESIGN Patients with resectable PHC on imaging who underwent operations in 2 high-volume centers (US and Europe) between 2000 and 2015 were included. Multivariable logistic regression analysis was used to develop the risk score. Cross-validation was used to validate the score, alternating the 2 centers as "training" and "testing" datasets. RESULTS Of 566 patients who underwent operations, 309 (55%) patients had a resection, and in 257 (45%) patients, a curative-intent resection was precluded due to distant metastasis (n = 151 [27%]) or locally advanced disease (n = 106 [19%]). Preoperative predictors included bilirubin >2 mg/dL, bile duct involvement on imaging, portal vein involvement on imaging (≥180 degrees), hepatic artery involvement on imaging (≥180 degrees), and suspicious lymph nodes on imaging. The new risk score (c-index 0.75 after cross-validation) provided significantly more accurate predictions than the Bismuth classification (c-index 0.62), Blumgart T-staging (c-index 0.67), and cTNM staging (c-index 0.68). The new risk score identified 4 risk groups for occult metastatic or locally advanced disease: low (14.7%), intermediate (29.5%), high (47.3%), and very high risk (81.3%). The preoperative score groups also predicted survival after operation, irrespective of intraoperative findings (p < 0.001). CONCLUSIONS The validated risk score can predict occult distant metastatic or locally advanced PHC based on 5 preoperatively available factors. The score can be useful in preoperative shared decision making and selection of patients in neoadjuvant clinical trials.
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Affiliation(s)
- Jimme K Wiggers
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David van Klaveren
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Robert J Coelen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - C Yung Nio
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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Kimbrough CW, Cloyd JM, Pawlik TM. Surgical approaches for the treatment of perihilar cholangiocarcinoma. Expert Rev Anticancer Ther 2018; 18:673-683. [DOI: 10.1080/14737140.2018.1473039] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Charles W. Kimbrough
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M. Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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46
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Rassam F, Roos E, van Lienden KP, van Hooft JE, Klümpen HJ, van Tienhoven G, Bennink RJ, Engelbrecht MR, Schoorlemmer A, Beuers UHW, Verheij J, Besselink MG, Busch OR, van Gulik TM. Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience. Langenbecks Arch Surg 2018; 403:289-307. [PMID: 29350267 PMCID: PMC5986829 DOI: 10.1007/s00423-018-1649-2] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 09/15/2017] [Indexed: 12/12/2022]
Abstract
AIM Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires aggressive surgical treatment in order to achieve curation. The assessment and work-up of patients with presumed PHC is multidisciplinary, complex and requires extensive experience. The aim of this paper is to review current aspects of diagnosis, preoperative work-up and extended resection in patients with PHC from the perspective of our own institutional experience with this complex tumor. METHODS We provided a review of applied modalities in the diagnosis and work-up of PHC according to current literature. All patients with presumed PHC in our center between 2000 and 2016 were identified and described. The types of resection, surgical techniques and outcomes were analyzed. RESULTS AND CONCLUSION Upcoming diagnostic modalities such as Spyglass and combinations of serum biomarkers and molecular markers have potential to decrease the rate of misdiagnosis of benign, inflammatory disease. Assessment of liver function with hepatobiliary scintigraphy provides better information on the future remnant liver (FRL) than volume alone. The selective use of staging laparoscopy is advisable to avoid futile laparotomies. In patients requiring extended resection, selective preoperative biliary drainage is mandatory in cholangitis and when FRL is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL volume is less than 40% and optionally includes the left portal vein branches to segment 4. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive lymph nodes preclude long-term survival. The benefit of unconditional en bloc resection of the portal vein bifurcation is uncertain. Along these lines, an aggressive surgical approach encompassing extended liver resection including segment 1, regional lymphadenectomy and conditional portal venous resection translates into favorable long-term survival.
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Affiliation(s)
- F Rassam
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
| | - E Roos
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - K P van Lienden
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - J E van Hooft
- Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands
| | - H J Klümpen
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - G van Tienhoven
- Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands
| | - R J Bennink
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - M R Engelbrecht
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - A Schoorlemmer
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - U H W Beuers
- Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands
| | - J Verheij
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - M G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - O R Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - T M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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Wang JK, Hu HJ, Shrestha A, Ma WJ, Yang Q, Liu F, Cheng NS, Li FY. Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma? Oncotarget 2018; 8:45335-45344. [PMID: 28484084 PMCID: PMC5542190 DOI: 10.18632/oncotarget.17336] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 04/11/2017] [Indexed: 02/05/2023] Open
Abstract
Background To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. Results In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216–9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391–28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107–14.459; P = 0.034). Materials and Methods Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. Conclusions In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.
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Affiliation(s)
- Jun-Ke Wang
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Anuj Shrestha
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.,Department of General Surgery, Gandaki Medical College, Pokhara, Nepal
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Qin Yang
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Nan-Sheng Cheng
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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48
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Mertens JC, Ilyas SI, Gores GJ. Targeting cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 2018; 1864:1454-1460. [PMID: 28844952 PMCID: PMC6013079 DOI: 10.1016/j.bbadis.2017.08.027] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 08/16/2017] [Accepted: 08/21/2017] [Indexed: 02/06/2023]
Abstract
Cholangiocarcinoma (CCA) represents a diverse group of epithelial cancers associated with the biliary tract, and can best be stratified anatomically into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) subsets. Molecular profiling has identified genetic aberrations associated with these anatomic subsets. For example, IDH catalytic site mutations and constitutively active FGFR2 fusion genes are predominantly identified in iCCA, whereas KRAS mutations and PRKACB fusions genes are identified in pCCA and dCCA. Clinical trials targeting these specific driver mutations are in progress. However, The Tumor Genome Atlas (TCGA) marker analysis of CCA also highlights the tremendous molecular heterogeneity of this cancer rendering comprehensive employment of targeted therapies challenging. CCA also display a rich tumor microenvironment which may be easier to target. For example, targeting cancer associated fibroblasts for apoptosis with BH3-mimetics and/or and reversing T-cell exhaustion with immune check point inhibitors may help aid in the treatment of this otherwise devastating malignancy. Combinatorial therapy attacking the tumor microenvironment plus targeted therapy may help advance treatment for CCA. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
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Affiliation(s)
- Joachim C Mertens
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland.
| | - Sumera I Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Chen P, Li B, Zhu Y, Chen W, Liu X, Li M, Duan X, Yi B, Wang J, Liu C, Luo X, Li X, Li J, Liang L, Yin X, Wang H, Jiang X. Establishment and validation of a prognostic nomogram for patients with resectable perihilar cholangiocarcinoma. Oncotarget 2018; 7:37319-37330. [PMID: 27144432 PMCID: PMC5095079 DOI: 10.18632/oncotarget.9104] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 04/13/2016] [Indexed: 12/15/2022] Open
Abstract
As the conventional staging systems have poor prognosis prediction ability for patients with perihilar cholangiocarcinoma (pCCA), we established and validated an effective prognostic nomogram for pCCA patients based on their personal and tumor characteristics. A total of 235 patients who received curative intent resections at the Eastern Hepatobiliary Surgery Hospital from 2000 to 2009 were recruited as the primary training cohort. Age, preoperative CA19-9 levels, portal vein involvement, hepatic artery invasion, lymph node metastases, and surgical treatment outcomes (R0 or R1/2) were independent prognostic factors for pCCA patients in the primary cohort as suggested by the multivariate analyses and these were included in the established nomogram. The calibration curve showed good agreement between overall survival probability of pCCA patients for the nomogram predictions and the actual observations and the concordance index (C-index) was 0.68 (95% CI, 0.61-0.71). The C-index values and time-dependent ROC tests suggested that the nomogram is superior to the conventional staging systems including the Bismuth-Corlette, Gazzaniga, Memorial Sloan Kettering Cancer Center (MSKCC), American Joint Committee on Cancer (AJCC) TNM 7th edition, and Mayo Clinic. The nomogram also performed better than the traditional staging system in the internal cohort with 93 pCCA patients from the same institution and an external validation cohort including 84 pCCA patients from another institution in predicting the overall survival of the pCCA patients as suggested by the C-index values and the time-dependent ROC tests. In summary, the proposed nomogram has superior predictive accuracy of prognosis for resectable pCCA patients.
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Affiliation(s)
- Peizhan Chen
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China
| | - Bin Li
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China.,Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China.,Diagnosis and Treatment Center of Malignant Biliary Tract Diseases, Secondary Military Medical University, Shanghai, 200433, P. R. China
| | - Yan Zhu
- Department of Pathology, Changhai Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China
| | - Wei Chen
- Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, P. R. China
| | - Xin Liu
- Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, P. R. China
| | - Mian Li
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China
| | - Xiaohua Duan
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China
| | - Bin Yi
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China.,Diagnosis and Treatment Center of Malignant Biliary Tract Diseases, Secondary Military Medical University, Shanghai, 200433, P. R. China
| | - Jinghan Wang
- Department of Hepatobiliary Surgery, Navy General Hospital, 100048, P. R. China
| | - Chen Liu
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China.,Diagnosis and Treatment Center of Malignant Biliary Tract Diseases, Secondary Military Medical University, Shanghai, 200433, P. R. China
| | - Xiangji Luo
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China.,Diagnosis and Treatment Center of Malignant Biliary Tract Diseases, Secondary Military Medical University, Shanghai, 200433, P. R. China
| | - Xiaoguang Li
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China
| | - Jingquan Li
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China
| | - Lijian Liang
- Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, P. R. China
| | - Xiaoyu Yin
- Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, P. R. China
| | - Hui Wang
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, P. R. China.,Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, 100021, P. R. China.,School of Life Science and Technology, ShanghaiTech University, Shanghai, 200031, P. R. China
| | - Xiaoqing Jiang
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, 200433, P. R. China.,Diagnosis and Treatment Center of Malignant Biliary Tract Diseases, Secondary Military Medical University, Shanghai, 200433, P. R. China
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Razumilava N, Lazaridis KN, Gores GJ. Cholangiocarcinoma. ZAKIM AND BOYER'S HEPATOLOGY 2018:693-707.e4. [DOI: 10.1016/b978-0-323-37591-7.00047-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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