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Dasari BVM, Line PD, Sapisochin G, Hibi T, Bhangui P, Halazun KJ, Shetty S, Shah T, Magyar CTJ, Donnelly C, Chatterjee D. Liver transplantation as a treatment for cancer: comprehensive review. BJS Open 2025; 9:zraf034. [PMID: 40380811 PMCID: PMC12084677 DOI: 10.1093/bjsopen/zraf034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres. METHODS A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma. RESULTS Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored. CONCLUSION Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.
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Affiliation(s)
- Bobby V M Dasari
- Department of Liver Transplantation and HBP Surgery, Queen Elizabeth Hospital, Birmingham, UK
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Gonzalo Sapisochin
- Department of Surgery, Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Prashant Bhangui
- Liver Transplantation and Hepatobiliary Surgery, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon (Delhi NCR), India
| | - Karim J Halazun
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Shishir Shetty
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Christian T J Magyar
- Department of Abdominal Transplant & HBP Surgical Oncology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | - Conor Donnelly
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Dev Chatterjee
- BRC Clinical Fellow Liver Medicine, University Hospitals of Birmingham, Birmingham, UK
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Liu JJ, Zhou M, Yuan T, Huang ZY, Zhang ZY. Conversion treatment for advanced intrahepatic cholangiocarcinoma: Opportunities and challenges. World J Gastroenterol 2025; 31:104901. [PMID: 40309227 PMCID: PMC12038554 DOI: 10.3748/wjg.v31.i15.104901] [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: 01/05/2025] [Revised: 02/22/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
The prevalence of intrahepatic cholangiocarcinoma (ICC) is increasing globally. Despite advancements in comprehending this intricate malignancy and formulating novel therapeutic approaches over the past few decades, the prognosis for ICC remains poor. Owing to the high degree of malignancy and insidious onset of ICC, numerous cases are detected at intermediate or advanced stages of the disease, hence eliminating the chance for surgical intervention. Moreover, because of the highly invasive characteristics of ICC, recurrence and metastasis postresection are prevalent, leading to a 5-year survival rate of only 20%-35% following surgery. In the past decade, different methods of treatment have been investigated, including transarterial chemoembolization, transarterial radioembolization, radiotherapy, systemic therapy, and combination therapies. For certain patients with advanced ICC, conversion treatment may be utilized to facilitate surgical resection and manage disease progression. This review summarizes the definition of downstaging conversion treatment and presents the clinical experience and evidence concerning conversion treatment for advanced ICC.
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Affiliation(s)
- Jun-Jie Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Mi Zhou
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Tong Yuan
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Tian H, He Q, Wan C. Conversion therapy combined with ALPPS for the treatment of intrahepatic cholangiocarcinoma: a case report. Front Oncol 2025; 15:1542955. [PMID: 40190549 PMCID: PMC11968688 DOI: 10.3389/fonc.2025.1542955] [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: 12/10/2024] [Accepted: 02/26/2025] [Indexed: 04/09/2025] Open
Abstract
Rationale Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor with limited treatment options for advanced cases. Conversion therapy combining immunotherapy, targeted therapy, and chemotherapy offers a promising approach to enable surgical resection, which remains the only curative option. Patient concerns A 67-year-old male presented with right upper abdominal pain for two months. Imaging and biopsy confirmed advanced ICC (Stage IV), with a 98 mm tumor, lymphadenopathy, and elevated tumor markers (CA199: 1190.4 U/ml). The disease was deemed unresectable. Diagnosis The patient was diagnosed with advanced ICC involving a large hepatic mass, lymph node metastasis, and insufficient liver reserve for conventional resection. Interventions The patient received six months of oxaliplatin plus gemcitabine (GEMOX), lenvatinib, and toripalimab, achieving significant tumor regression. A two-step ALPPS procedure was then performed, comprising portal vein ligation and right hepatectomy. Outcomes The treatment reduced tumor size (98 mm to 60 mm), normalized tumor markers, and improved liver reserve. Postoperative pathology confirmed >80% tumor remission with negative margins. At 12 months post-surgery, the patient remained disease-free. Lessons This case demonstrates that advanced ICC can be downstaged with systemic therapy, enabling resection via ALPPS. The combination of GEMOX, lenvatinib, and toripalimab is an effective and safe conversion therapy regimen. This approach may serve as a model for managing similar advanced cases.
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Affiliation(s)
- Hengyu Tian
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qinghua He
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shenzhen Traditional Chinese Medicine Hospital/The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Chidan Wan
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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4
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Altaf A, Endo Y, Guglielmi A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Alexandrescu S, Weiss MJ, Kitago M, Poultsides G, Maithel SK, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM. Upfront surgery for intrahepatic cholangiocarcinoma: Prediction of futility using artificial intelligence. Surgery 2025; 179:108809. [PMID: 39322483 DOI: 10.1016/j.surg.2024.06.059] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/15/2024] [Accepted: 06/18/2024] [Indexed: 09/27/2024]
Abstract
OBJECTIVE We sought to identify patients at risk of "futile" surgery for intrahepatic cholangiocarcinoma using an artificial intelligence (AI)-based model based on preoperative variables. METHODS Intrahepatic cholangiocarcinoma patients who underwent resection between 1990 and 2020 were identified from a multi-institutional database. Futility was defined either as mortality or recurrence within 12 months of surgery. Various machine learning and deep learning techniques were used to develop prediction models for futile surgery. RESULTS Overall, 827 intrahepatic cholangiocarcinoma patients were included. Among 378 patients (45.7%) who had futile surgery, 297 patients (78.6%) developed intrahepatic cholangiocarcinoma recurrence and 81 patients (21.4%) died within 12 months of surgical resection. An ensemble model consisting of multilayer perceptron and gradient boosting classifiers that used 10 preoperative factors demonstrated the highest accuracy, with areas under receiver operating characteristic curves of 0.830 (95% confidence interval 0.798-0.861) and 0.781 (95% confidence interval 0.707-0.853) in the training and testing cohorts, respectively. The model displayed sensitivity and specificity of 64.5% and 80.0%, respectively, with positive and negative predictive values of 73.1% and 72.7%, respectively. Radiologic tumor burden score, serum carbohydrate antigen 19-9, and direct bilirubin levels were the factors most strongly predictive of futile surgery. The artificial intelligence-based model was made available online for ease of use and clinical applicability (https://altaf-pawlik-icc-futilityofsurgery-calculator.streamlit.app/). CONCLUSION The artificial intelligence ensemble model demonstrated high accuracy to identify patients preoperatively at high risk of undergoing futile surgery for intrahepatic cholangiocarcinoma. Artificial intelligence-based prediction models can provide clinicians with reliable preoperative guidance and aid in avoiding futile surgical procedures that are unlikely to provide patients long-term benefits.
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Affiliation(s)
- Abdullah Altaf
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH. https://twitter.com/AbdullahAltaf97
| | - Yutaka Endo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH. https://twitter.com/YutakaEndoSurg
| | | | | | - Todd W Bauer
- Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | | | - Mathew J Weiss
- Department of Surgery, Johns Hopkins Medicine, Baltimore, MD
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, CA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Surgery, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas G Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Itaru Endo
- Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH.
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5
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Altaf A, Khalil M, Akabane M, Rashid Z, Kawashima J, Zindani S, Ruzzenente A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Popescu I, Weiss MJ, Kitago M, Poultsides G, Maithel SK, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM. Textbook outcome in liver surgery for intrahepatic cholangiocarcinoma: defining predictors of an optimal postoperative course using machine learning. HPB (Oxford) 2025; 27:402-413. [PMID: 39755480 DOI: 10.1016/j.hpb.2024.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/12/2024] [Accepted: 12/12/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND We sought to define textbook outcome in liver surgery (TOLS) for intrahepatic cholangiocarcinoma (ICC) by considering the implications of perioperative outcomes on overall survival (OS). METHODS Using a multi-institutional database, TOLS for ICC was defined by employing novel machine learning (ML) models to identify perioperative factors most strongly predictive of OS ≥ 12 months. Subsequently, clinicopathologic factors associated with achieving TOLS were investigated. RESULTS A total of 1556 patients with ICC were included. The ML classification models demonstrated that the absence of post-hepatectomy liver failure, intraoperative blood loss <750 mL, absence of major infectious complications, and R0 resection were the perioperative outcomes associated with prolonged OS, thereby defining TOLS for ICC. On multivariable analysis, older age, ASA class >2, lymph node metastasis, receipt of neoadjuvant therapy, advanced T status, poor histological grade and microvascular invasion were independently associated with lower odds of achieving TOLS (all p-values<0.05). Overall, 60.2 % (n = 936) of the patients achieved TOLS, demonstrating markedly improved OS and recurrence-free survival (RFS) than individuals who did not (both p < 0.05). CONCLUSION A standardized definition of TOLS for ICC was established that may be used to evaluate hospital performance at the patient level and help optimize surgical outcomes for patients with ICC.
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Affiliation(s)
- Abdullah Altaf
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Mujtaba Khalil
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Miho Akabane
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Zayed Rashid
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jun Kawashima
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Shahzaib Zindani
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | | | | | - Todd W Bauer
- Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Matthew J Weiss
- Department of Surgery, Northwell Health, Long Island, NY, USA
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Surgery, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas G Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Itaru Endo
- Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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6
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [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: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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Girod BJ, Kandathil A. A review of F-18 fluorodeoxyglucose PET/CT in the evaluation and treatment of hepatobiliary tumors. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:245-258. [PMID: 39846364 DOI: 10.23736/s1824-4785.24.03574-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2025]
Abstract
Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) pose significant diagnostic and therapeutic challenges. Magnetic resonance imaging (MRI) and multiphase computed tomography (CT) have been the preferred imaging modalities for diagnosis, staging, and surveillance of patients with these malignancies. The best clinical outcomes depend on the appropriate selection of treatment options from the tools available in neo-adjuvant therapy, surgical resection, locoregional therapy, liver transplantation, and adjuvant therapy. While not a part of the routine diagnostic work-up or follow-up, F-18 fluorodeoxyglucose positron emission tomography (FDG PET/CT) can inform therapeutic decision making and help avoid futile surgeries by detecting unsuspected distant metastases. Additionally, metabolic information obtained with FDG PET/CT has prognostic value, predicting treatment response and survival. In patients with HCC metabolic parameters obtained by FDG PET/CT have been shown to correlate with microvascular invasion and predict recurrence in orthotopic transplant recipients. This article will highlight studies that have evaluated the role of FDG PET/CT in diagnosis, staging and therapeutic response assessment in patients with hepatobiliary cancers.
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Affiliation(s)
- Bradley J Girod
- Nuclear Medicine, Radiology, University of Texas Southwestern, Dallas, TX, USA -
| | - Asha Kandathil
- Nuclear Medicine, Radiology, University of Texas Southwestern, Dallas, TX, USA
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Sheng R, Zheng B, Zhang Y, Sun W, Yang C, Zeng M. A preliminary study of developing an MRI-based model for postoperative recurrence prediction and treatment direction of intrahepatic cholangiocarcinoma. LA RADIOLOGIA MEDICA 2024; 129:1766-1777. [PMID: 39487376 DOI: 10.1007/s11547-024-01910-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024]
Abstract
PURPOSE To establish an MRI-based predictive model for postoperative recurrence in intrahepatic cholangiocarcinoma (iCCA) and further to evaluate the model utility in treatment direction for neoadjuvant and adjuvant therapies. MATERIALS AND METHODS Totally 114 iCCA patients with curative surgery were retrospectively included, including 38 patients in the neoadjuvant treatment, traditional surgery, and adjuvant treatment groups for each. Predictive variables associated with postoperative recurrence were identified using univariate and multivariate Cox regression analyses, and a prognostic model was formulated. Recurrence-free survival (RFS) curves were compared using log-rank test between MRI-predicted high-risk and low-risk iCCAs stratified by the optimal threshold. RESULTS Tumor multiplicity (hazard ratio (HR) = 1.671 [95%CI 1.036, 2.695], P = 0.035), hemorrhage (HR = 2.391 [95%CI 1.189, 4.810], P = 0.015), peri-tumor diffusion-weighted hyperintensity (HR = 1.723 [95%CI 1.085, 2.734], P = 0.021), and positive regional lymph node (HR = 2.175 [95%CI 1.295, 3.653], P = 0.003) were independently associated with postoperative recurrence; treatment group was not significantly related to recurrence (P > 0.05). Independent variables above were incorporated for the recurrence prediction model, the 1-year and 2-year time-dependent area under the curve values were 0.723 (95%CI 0.631, 0.815) and 0.725 (95%CI 0.634, 0.816), respectively. After risk stratification, the MRI-predicted high-risk iCCA patients had higher cumulative incidences of recurrence and worse RFS than the low-risk patients (P < 0.001 for both). In the MRI-predicted high-risk patients, neoadjuvant therapy was associated with improved all-stage RFS (P = 0.034), and adjuvant therapy was associated with improved RFS after 4 months (P = 0.014). CONCLUSIONS The MRI-based iCCA recurrence predictive model may serve as a decision-making tool for both personalized prognostication and therapy selection.
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Affiliation(s)
- Ruofan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Beixuan Zheng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yunfei Zhang
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Wei Sun
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
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Lin J, Tao H, Yuan X, Yang J. Laparoscopic Radical Resection After Neoadjuvant Therapy for Intrahepatic Cholangiocarcinoma with Hepatic Hilus Involvement. Ann Surg Oncol 2024; 31:6564-6565. [PMID: 39117927 DOI: 10.1245/s10434-024-15772-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 06/26/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICCA) with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma with worse outcomes.1,2 Surgical resection with negative margins is the only effective treatment for ICCA.3,4 Neoadjuvant therapy is considered to improve the possibility of surgery for patients;5,6 however, laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement remains at the exploratory stage due to technical challenges.7 METHODS: A 19-year-old man presented with an ICCA on the left side of the liver invading the blood vessels and bile ducts in the hepatic hilum. Five courses of neoadjuvant therapy were administered after a multidisciplinary team determined that the tumor was extremely difficult and risky to operate on. A laparoscopic left hepatectomy plus caudal lobectomy was performed to complete the resection of the negative margins. Three-dimensional visualization enabled precise preoperative planning and intraoperative guidance, including visualization of the tumor location, simulation of bile duct and vessel dissection steps, as well as determining the extent of liver resection. Vascular skeletonization, lymphadenectomy and biliary reconstruction were performed during operation. RESULTS The operation time was 415 min with a blood loss of 100 mL. Postoperative pathohistology confirmed cholangiocarcinoma with low to intermediate differentiation. The resection margin was negative (R0) and lymph node pathology was tumor-negative (0/10). The patient was discharged on postoperative day 10 without complications. CONCLUSION Laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement is safe and feasible in a large-throughput hepatic surgery center.
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Affiliation(s)
- Jinyu Lin
- Department of Hepatobiliary Surgery (1), Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Haisu Tao
- Department of Hepatobiliary Surgery (1), Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Xiangdong Yuan
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
| | - Jian Yang
- Department of Hepatobiliary Surgery (1), Zhujiang Hospital, Southern Medical University, Guangzhou, China.
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China.
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Sposito C, Maspero M, Cucchetti A, Mazzaferro V. A snapshot on current approaches to lymphadenectomy in liver resection for intrahepatic cholangiocarcinoma: results from an international survey. Updates Surg 2024; 76:1797-1805. [PMID: 38713394 PMCID: PMC11455682 DOI: 10.1007/s13304-024-01852-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/10/2024] [Indexed: 05/08/2024]
Abstract
The use of lymphadenectomy (LND) during resection of intrahepatic cholangiocarcinoma (ICC) is still debated, leading to differing practices in different centers and countries. The aim of this study was to assess such differences. A survey on LND for ICC was distributed to the members of the International Hepato-PancreatoBiliary Association (IHPBA) and the Italian Chapter of IHPBA (AICEP). Two-hundred thirty-four surgeons completed the survey (88% males; median age 46 years). Preoperative nodal staging was deemed mandatory/very important by 65%. Adequate LND was defined as hepatoduodenal ligament LND by 33%, LND at specific nodal stations by 28% and retrieval of > 5 nodes by 28%. The decision to perform LND was influenced by comorbidities (48%), chronic liver disease (38%) and satellitosis (32%). Most participants modify perioperative management in case of clinically positive nodes, 50% stating they would give neoadjuvant therapy. The role of LND in clinically node negative disease was adequate staging for 88%, survival benefit for 50.5% and clinical trials eligibility for 18.5%. Our survey confirms heterogeneity in the evaluation of role and extent of LND for ICC, how this relates to subjective perception of importance of LND, and need of a systematic approach in this area.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy.
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
| | - Marianna Maspero
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni, Pierantoni Hospital, Forlì, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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11
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Dharmapuri S, Cabal R, Akturk G, Ioannou G, Ozbey S, Paulsen J, Raina S, Ang C, Sarpel U, Sung MW, Kozuch P, Schwartz ME, Cohen DJ, Gnjatic S, Pintova S. Multiplexed immunohistochemical analysis of the immune microenvironment of biliary tract cancers pre- & post-neoadjuvant chemotherapy: case series. ANNALS OF TRANSLATIONAL MEDICINE 2024; 12:78. [PMID: 39118963 PMCID: PMC11304425 DOI: 10.21037/atm-23-1928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 03/17/2024] [Indexed: 08/10/2024]
Abstract
Background Neoadjuvant chemotherapy (NACT) is increasingly being used in the management of locally advanced biliary tract cancer (BTC). The evidence suggests a contributing role of tumor infiltrating immune cells in the prognosis and response. We set out to characterize immune modulation of tumor immune microenvironment in BTC following NACT. Case Description Patients with BTC who underwent diagnostic biopsy, then NACT then resection between 2014-2018 were identified. Multiplexed immunohistochemical consecutive staining on single slide (MICSSS) analysis was performed with a series of immune markers to characterize T-cells, immune checkpoints etc. on pre- & post-NACT tumor tissue. Density was calculated for each marker. The final analysis included five patients. Median age was 48 (range, 41-56) years, with 4 female, 4 intrahepatic cholangiocarcinoma and 1 gallbladder. All patients received gemcitabine/cisplatin as NACT (median of 5 cycles). Median time from diagnosis to surgery was 4.3 (range, 1.4-7.8) months. All patients were mismatch repair proficient (pMMR). NACT on average produced a depletion of all immune markers. Given small sample size, each patient was considered their own control and changes in mean cell densities post-NACT were calculated. Patient #2 with a 40-fold increase in PD-L1 expression & 5-fold decrease in CD8:FOXP3 ratio after NACT notably had the shortest disease-free interval (DFI). Patient #3 with the longest DFI had the largest increase in CD8:FOXP3 by about 8-fold with a decrease in PD-L1. Conclusions Preliminary results suggest NACT may differentially modulate various compartments of the immune tumor contexture despite overall cell depletion. Future studies should focus on strategies to expand immune modulation of tumor microenvironment, including immune-oncology agents to augment the effects of chemotherapy.
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Affiliation(s)
- Sirish Dharmapuri
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Rafael Cabal
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Guray Akturk
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Giorgio Ioannou
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Sinem Ozbey
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - John Paulsen
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Sheen Raina
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Celina Ang
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Max W. Sung
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Peter Kozuch
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Myron E. Schwartz
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Deirdre Jill Cohen
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
| | - Sacha Gnjatic
- Division of Molecular and Cell-Based Medicine, Department of Pathology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA
| | - Sofya Pintova
- Division of Medical Oncology, Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai West, Tisch Cancer Institute, New York, NY, USA
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12
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Verma S, Grindrod N, Breadner D, Lock M. The Current Role of Radiation in the Management of Cholangiocarcinoma-A Narrative Review. Cancers (Basel) 2024; 16:1776. [PMID: 38730728 PMCID: PMC11083065 DOI: 10.3390/cancers16091776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/30/2024] [Accepted: 05/01/2024] [Indexed: 05/13/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors.
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Affiliation(s)
- Saurav Verma
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada; (S.V.); (N.G.); (D.B.)
- London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Natalie Grindrod
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada; (S.V.); (N.G.); (D.B.)
- London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Daniel Breadner
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada; (S.V.); (N.G.); (D.B.)
- London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Michael Lock
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada; (S.V.); (N.G.); (D.B.)
- London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
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13
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Jones RP. Lesional liver biopsies: better treatments, better studies, better science. Br J Surg 2024; 111:znae063. [PMID: 38752385 DOI: 10.1093/bjs/znae063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 01/20/2024] [Accepted: 01/23/2024] [Indexed: 12/05/2024]
Affiliation(s)
- Robert P Jones
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Department of Hepatobiliary Surgery, Liverpool University Teaching Hospitals NHS Foundation Trust, Liverpool, UK
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14
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Elshami M, Ammori JB, Hardacre JM, Selfridge JE, Bajor D, Mohamed A, Chakrabarti S, Mahipal A, Winter JM, Ocuin LM. Surgical Resection Alone is Associated With Higher Long-Term Survival Than Multiagent Chemotherapy Alone for Patients With Localized Biliary Tract Cancers. J Surg Res 2024; 295:705-716. [PMID: 38141457 DOI: 10.1016/j.jss.2023.11.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/17/2023] [Accepted: 11/12/2023] [Indexed: 12/25/2023]
Abstract
INTRODUCTION We compared long-term survival of patients with localized biliary tract cancers (BTCs) treated with either surgical resection or multiagent chemotherapy. METHODS Patients with localized BTC [gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2017). Piecewise-constant hazard modeling was used to estimate hazard ratios (HRs) at prespecified intervals: 0-30 d, 31-60 d, 61-90 d, and >90 d post-treatment. RESULTS A total of 5988 patients with localized BTC were identified: 2697 (45.0%) received multiagent chemotherapy and 3291 (55.0%) underwent surgical resection. Patients with gallbladder adenocarcinoma or extrahepatic cholangiocarcinoma who were treated with surgical resection had an associated decline in overall survival (OS) as compared to those treated with multiagent chemotherapy within 0-30 d of treatment initiation (gallbladder adenocarcinoma [adjusted HR = 3.94, 95% confidence interval [CI]: 1.77-8.80]; extrahepatic cholangiocarcinoma [adjusted HR = 4.88, 95% CI: 2.76-8.61]). However, there was an associated improvement in OS for patients treated with surgical resection after 90 d from treatment initiation (gallbladder adenocarcinoma [adjusted HR = 0.36, 95% CI: 0.28-0.46]; extrahepatic cholangiocarcinoma [adjusted HR = 0.27, 95% CI: 0.24-0.32]). Among patients with intrahepatic cholangiocarcinoma, those who underwent surgical resection had an associated improvement in OS at 31-60 d (adjusted HR = 0.63, 95% CI: 0.40-0.99) and a further associated increase in OS at 61-90 d (adjusted HR = 0.34, 95% CI: 0.21-0.54) and after 90 d (HR = 0.23, 95% CI: 0.21-0.27) of treatment initiation. CONCLUSIONS For patients with localized BTC, surgical resection alone is associated with improved long-term survival outcomes compared to multiagent chemotherapy alone.
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Affiliation(s)
- Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - J Eva Selfridge
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - David Bajor
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amit Mahipal
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Jordan M Winter
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
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15
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Ruff SM, Cloyd JM, Pawlik TM. Annals of Surgical Oncology Practice Guidelines Series: Management of Primary Liver and Biliary Tract Cancers. Ann Surg Oncol 2023; 30:7935-7949. [PMID: 37691030 DOI: 10.1245/s10434-023-14255-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 08/22/2023] [Indexed: 09/12/2023]
Abstract
Primary cancers of the liver and biliary tract are rare and aggressive tumors that often present with locally advanced or metastatic disease. For patients with localized disease amenable to resection, surgery typically offers the best chance at curative-intent therapy. Unfortunately, the incidence of recurrence even after curative-intent surgery remains high. In turn, patients with hepatobiliary cancers commonly require multimodality therapy including a combination of resection, systemic therapy (i.e., targeted therapy, cytotoxic chemotherapy, immunotherapy), and/or loco-regional therapies. With advancements in the field, it is crucial for surgical oncologists to remain updated on the latest guidelines and recommendations for surgical management and optimal patient selection. Given the complex and evolving nature of treatment, this report highlights the latest practice guidelines for the surgical management of hepatobiliary cancers.
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Affiliation(s)
- Samantha M Ruff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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16
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White MJ, Jensen EH, Brauer DG. A Review of Resection and Surgical Ablation for Primary and Secondary Liver Cancers. Semin Intervent Radiol 2023; 40:536-543. [PMID: 38274223 PMCID: PMC10807965 DOI: 10.1055/s-0043-1777747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
The surgical management of primary and secondary liver tumors is constantly evolving. Patient selection, particularly with regard to determining resectability, is vital to the success of programs directed toward invasive treatments of liver tumors. Particular attention should be paid toward determining whether patients are best served with surgical resection or ablative therapies. A multidisciplinary approach is necessary to provide optimal care to patients with liver malignancy.
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Affiliation(s)
- McKenzie J. White
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Eric H. Jensen
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - David G. Brauer
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
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17
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Dhote A, Tzedakis S, Hobeika C, Marchese U, Coriat R, Nassar A, Beaufrère A, Codjia T, Goumard C, Scatton O, Dohan A, Ronot M, Terris B, Lesurtel M, Dokmak S, Cauchy F, Fuks D. Impact of induction therapy in locally advanced intrahepatic cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106939. [PMID: 37268522 DOI: 10.1016/j.ejso.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 05/13/2023] [Accepted: 05/19/2023] [Indexed: 06/04/2023]
Abstract
INTRODUCTION After local or systemic treatment, a small number of patients with primarily unresectable intrahepatic cholangiocarcinoma (ICC) may benefit from secondary resection. This study aimed to analyze the oncological outcome of patients who underwent radical surgery after preoperative treatment. METHODS From 2000 to 2021, all patients who underwent curative-intent liver resection for ICC in three tertiary centers were selected. Patients were divided into two groups: upfront surgery (US) and preoperative treatment (POT). Oncologic data (preoperative treatment, histologic data, adjuvant chemotherapy, overall survival, and recurrence-free survival) were compared between the two groups. RESULTS Among 198 included patients, 31 (15.7%) received POT including chemotherapy (74.2%), radioembolization (12.9%), chemoembolization (9.7%), or combined radiotherapy and chemotherapy (3.2%). Major resection was performed in 156 (78.8%) patients, and 53 (26.8%) had vascular and/or biliary reconstruction. Histological findings were similar between US and POT group and were not affected by the type of POT. After a median follow-up of 23 months, recurrence rate (58.1% POT vs. 55.1% US, p = 0.760) and type were similar between groups. Recurrence-free survival at 1 and 3 years (41.9% and 22.6% vs. 46.7 and 21.6% in the POT and US, respectively, p = 0.989) and overall survival at 1 and 3 years (77.4% and 32.3% vs. 69.5% and 34.7% in the POT and US respectively, p = 0.323) were similar and independent of the POT type. CONCLUSION After POT, downstaged patients who underwent curative-intent resection for initially unresectable ICC have similar long-term outcomes as those undergoing upfront surgery.
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Affiliation(s)
- Alix Dhote
- Service De Chirurgie Digestive, Hépatobiliaire Et Endocrinienne, Hôpital Cochin, Paris, France; Université Paris-Sorbonne, Paris, France.
| | - Stylianos Tzedakis
- Service De Chirurgie Digestive, Hépatobiliaire Et Endocrinienne, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Christian Hobeika
- Service De Chirurgie Digestive, Hépato-Bilio-Pancréatique Et Transplantation Hépatique, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - Ugo Marchese
- Service De Chirurgie Digestive, Hépatobiliaire Et Endocrinienne, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Romain Coriat
- Service De Cancérologie, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Alexandra Nassar
- Service De Chirurgie Digestive, Hépatobiliaire Et Endocrinienne, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Aurélie Beaufrère
- Service d'Anatomie et cytologie pathologique, APHP.Nord, FHU MOSAIC, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - Tatiana Codjia
- Service De Chirurgie Digestive, Hépato-Bilio-Pancréatique Et Transplantation Hépatique, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - Claire Goumard
- Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, Paris, France; Université Paris-Sorbonne, Paris, France
| | - Olivier Scatton
- Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, Paris, France; Université Paris-Sorbonne, Paris, France
| | - Anthony Dohan
- Service De Radiologie, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Maxime Ronot
- Service De Radiologie, Hôpital Beaujon, APHP.Nord, Clichy, France; Université Paris Cité, Paris, France
| | - Benoit Terris
- Service d'Anatomie et cytologie pathologique, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
| | - Mickael Lesurtel
- Service De Chirurgie Digestive, Hépato-Bilio-Pancréatique Et Transplantation Hépatique, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - Safi Dokmak
- Service De Chirurgie Digestive, Hépato-Bilio-Pancréatique Et Transplantation Hépatique, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - François Cauchy
- Service De Chirurgie Digestive, Hépato-Bilio-Pancréatique Et Transplantation Hépatique, Hôpital Beaujon, Clichy, France; Université Paris Cité, Paris, France
| | - David Fuks
- Service De Chirurgie Digestive, Hépatobiliaire Et Endocrinienne, Hôpital Cochin, Paris, France; Université Paris Cité, Paris, France
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18
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Dhote A, Tzedakis S, Shapira OI, Nassar A, Boudjema K, Fuks D. Current status and perspectives in the surgical and oncological management of intrahepatic cholangiocarcinoma. J Visc Surg 2023; 160:346-355. [PMID: 37563006 DOI: 10.1016/j.jviscsurg.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor after hepatocellular carcinoma (HCC). Management depends on their resectability at the time of diagnosis. Two types can be distinguished by imaging: resectable ICCs amenable to surgery and locally advanced and/or metastatic ICCs, that are treated by chemotherapy, radiotherapy or loco-regional treatment (radioembolization, chemoembolization, intra-arterial chemotherapy and thermoablation). Over the last decade, the management strategy for these tumors has been modified by the appearance of loco-regional treatments as well as the introduction of immunotherapy that have shown their efficacy in the control of ICC. The aim of this review is to describe the current status of treatments for ICCs, as well as the different therapeutic strategies being assessed.
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Affiliation(s)
- Alix Dhote
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris-Sorbonne University, Paris, France
| | - Stylianos Tzedakis
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France
| | - Ortal Itzaki Shapira
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France
| | - Alexandra Nassar
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France
| | - Karim Boudjema
- Hepatobiliary and Digestive Surgery Department, Pontchaillou Hospital, Rennes 1 University, Rennes, France
| | - David Fuks
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France.
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19
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Zhang Z, Zhang W. Conversion therapy for advanced cholangiocarcinoma in the era of molecular targeted therapy and immune therapy. Hepatobiliary Surg Nutr 2023; 12:772-775. [PMID: 37886181 PMCID: PMC10598300 DOI: 10.21037/hbsn-23-352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 07/30/2023] [Indexed: 10/28/2023]
Affiliation(s)
- Zunyi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Research Center for Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Clinical Research Center for Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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20
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Alaimo L, Lima HA, Moazzam Z, Endo Y, Yang J, Ruzzenente A, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Kitago M, Pawlik TM. Development and Validation of a Machine-Learning Model to Predict Early Recurrence of Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2023; 30:5406-5415. [PMID: 37210452 DOI: 10.1245/s10434-023-13636-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/26/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND The high incidence of early recurrence after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a detrimental effect on overall survival (OS). Machine-learning models may improve the accuracy of outcome prediction for malignancies. METHODS Patients who underwent curative-intent hepatectomy for ICC were identified using an international database. Three machine-learning models were trained to predict early recurrence (< 12 months after hepatectomy) using 14 clinicopathologic characteristics. The area under the receiver operating curve (AUC) was used to assess their discrimination ability. RESULTS In this study, 536 patients were randomly assigned to training (n = 376, 70.1%) and testing (n = 160, 29.9%) cohorts. Overall, 270 (50.4%) patients experienced early recurrence (training: n = 150 [50.3%] vs testing: n = 81 [50.6%]), with a median tumor burden score (TBS) of 5.6 (training: 5.8 [interquartile range {IQR}, 4.1-8.1] vs testing: 5.5 [IQR, 3.7-7.9]) and metastatic/undetermined nodes (N1/NX) in the majority of the patients (training: n = 282 [75.0%] vs testing n = 118 [73.8%]). Among the three different machine-learning algorithms, random forest (RF) demonstrated the highest discrimination in the training/testing cohorts (RF [AUC, 0.904/0.779] vs support vector machine [AUC, 0.671/0.746] vs logistic regression [AUC, 0.668/0.745]). The five most influential variables in the final model were TBS, perineural invasion, microvascular invasion, CA 19-9 lower than 200 U/mL, and N1/NX disease. The RF model successfully stratified OS relative to the risk of early recurrence. CONCLUSIONS Machine-learning prediction of early recurrence after ICC resection may inform tailored counseling, treatment, and recommendations. An easy-to-use calculator based on the RF model was developed and made available online.
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Affiliation(s)
- Laura Alaimo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Henrique A Lima
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Zorays Moazzam
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Yutaka Endo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jason Yang
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | | | | | | | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | | | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
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21
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Choi WJ, Walker R, Rajendran L, Jones O, Gravely A, Englesakis M, Gallinger S, Hirschfield G, Hansen B, Sapisochin G. Call to Improve the Quality of Prediction Tools for Intrahepatic Cholangiocarcinoma Resection: A Critical Appraisal, Systematic Review, and External Validation Study. ANNALS OF SURGERY OPEN 2023; 4:e328. [PMID: 37746604 PMCID: PMC10513309 DOI: 10.1097/as9.0000000000000328] [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: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 09/26/2023] Open
Abstract
Objective To conduct a systematic review, critical appraisal, and external validation of survival prediction tools for patients undergoing intrahepatic cholangiocarcinoma (iCCA) resection. Summary background data Despite the development of several survival prediction tools in recent years for patients undergoing iCCA resections, there is a lack of critical appraisal and external validation of these models. Methods We conducted a systematic review and critical appraisal of survival and recurrence prediction models for patients undergoing curative-intent iCCA resections. Studies were evaluated based on their model design, risk of bias, reporting, performance, and validation results. We identified the best model and externally validated it using our institution's data. Results This review included a total of 31 studies, consisting of 26 studies with original prediction tools and 5 studies that only conducted external validations. Among the 26, 54% of the studies conducted internal validations, 46% conducted external validations, and only 1 study scored a low risk of bias. Harrell's C-statistics ranged from 0.67 to 0.76 for internal validation and from 0.64 to 0.75 for external validation. Only 81% of the studies reported model calibration. Our external validation of the best model (Intrahepatic Cholangiocarcinoma [ICC]-Metroticket) estimated Harrell's and Uno's C-statistics of 0.67 (95% CI: 0.56-0.77) and Uno's time-dependent area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.53-0.88), with a Brier score of 0.20 (95% CI: 0.15-0.26) and good calibration plots. Conclusions Many prediction models have been published in recent years, but their quality remains poor, and minimal methodological quality improvement has been observed. The ICC-Metroticket was selected as the best model (Uno's time-dependent AUC of 0.71) for 5-year overall survival prediction in patients undergoing curative-intent iCCA resection.
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Affiliation(s)
- Woo Jin Choi
- From the Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Richard Walker
- From the Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Luckshi Rajendran
- From the Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Owen Jones
- University Health Network, HPB Surgical Oncology, Toronto, Ontario, Canada
| | - Annie Gravely
- University Health Network, HPB Surgical Oncology, Toronto, Ontario, Canada
| | - Marina Englesakis
- Library and Information Services, University Health Network, Toronto, Canada
| | - Steven Gallinger
- From the Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- University Health Network, HPB Surgical Oncology, Toronto, Ontario, Canada
| | - Gideon Hirschfield
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Bettina Hansen
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
- Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands
| | - Gonzalo Sapisochin
- From the Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- University Health Network, HPB Surgical Oncology, Toronto, Ontario, Canada
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22
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Ioka T, Shindo Y, Ueno M, Nagano H. Current progress in perioperative chemotherapy for biliary tract cancer. Ann Gastroenterol Surg 2023; 7:565-571. [PMID: 37416744 PMCID: PMC10319609 DOI: 10.1002/ags3.12691] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/28/2023] [Accepted: 04/30/2023] [Indexed: 07/08/2023] Open
Abstract
Biliary tract cancer (BTCs) is a heterogeneous malignancy divided into cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Due to little or no symptoms, most patients with BTCs are diagnosed with unresectable or metastatic disease. Only 20%-30% of all BTCs are suitable for potentially resectable diseases. Although radical resection with a negative surgical margin is the only potentially curative method for BTCs, most patients develop postoperative recurrence, which is associated with poor prognosis. Therefore, perioperative treatment is necessary to improve survival. There are very few randomized phase III clinical trials of perioperative chemotherapy due to the relative rarity of BTCs. Adjuvant chemotherapy with S-1 for patients with resected BTC significantly increased overall survival compared with upfront surgery in a recent ASCOT trial. In East Asia, S-1 is currently considered the standard adjuvant chemotherapy, while capecitabine may still be used in other areas. Since then, our phase III trial (KHBO1401), gemcitabine and cisplatin plus S-1 (GCS) has become the standard chemotherapy for advanced BTCs. GCS not only improved overall survival but demonstrated a high response rate. The efficacy of GCS as a preoperative neoadjuvant chemotherapy for resectable BTCs has been investigated in a randomized phase III trial (JCOG1920) in Japan. In this review, we summarize the current and ongoing clinical trials focusing on adjuvant and neoadjuvant chemotherapy for BTCs.
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Affiliation(s)
- Tatsuya Ioka
- Department of Oncology CenterYamaguchi University HospitalUbeJapan
| | - Yoshitaro Shindo
- Department of Gastroenterological, Breast, and Endocrine SurgeryYamaguchi University Graduate School of MedicineUbeJapan
| | - Makoto Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology DivisionKanagawa Cancer CenterYokohamaJapan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast, and Endocrine SurgeryYamaguchi University Graduate School of MedicineUbeJapan
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23
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Yang Z, Jiang X. Efficacy and safety comparison of neoadjuvant chemotherapy followed by surgery and upfront surgery for treating intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. BMC Gastroenterol 2023; 23:122. [PMID: 37046191 PMCID: PMC10099833 DOI: 10.1186/s12876-023-02754-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 04/01/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND AND AIMS Currently, surgical resection is the most commonly performed and effective treatment for intrahepatic cholangiocarcinoma (ICC) worldwide. However, the prognosis of ICC is unsatisfactory. This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery and upfront surgery in treating intrahepatic cholangiocarcinoma (ICC). The study also intends to explore whether chemotherapy should be introduced before surgery and which populations should be considered for neoadjuvant chemotherapy. METHOD Four databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched from their inception dates to January 2022 for relevant articles. The statistical analysis was performed using the Review Manager Software (version5.3). The non-randomized interventions (ROBINS-I) was used to assess the methodological quality of included studies and the overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Moreover, the primary outcomes included 1-year, 3-year and 5-year overall survival (OS), while the secondary outcomes were R0 resection, 1-year, 3-year and 5-year recurrence-free survival (RFS), postoperative complications and ninety-day postoperative mortality. RESULTS Five studies involving 2412 patients were included in this meta-analysis. There was no significant difference in 1-year OS, 3-year OS, 1-year, 3-year and 5-year RFS, postoperative complications and ninety-day postoperative mortality between the two groups. However, the meta-analysis showed that the neoadjuvant chemotherapy group had a better 5-year OS benefit in ICC patients than the upfront surgery group (OR = 1.27, 95% CI: 1.02-1.58), while the R0 resection rate was lower in neoadjuvant chemotherapy group than that in the upfront surgery group (OR = 0.49, 95% CI: 0.26-0.91). CONCLUSION Compared with the upfront surgery, neoadjuvant chemotherapy followed by surgery could prolong the 5-year OS without increasing the risk of postoperative complications in ICC patients. Considering that the patients in the neoadjuvant chemotherapy followed by surgery group had more advanced ICC cases, the benefits of neoadjuvant chemotherapy may be more significant in patients with more advanced ICC.
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Affiliation(s)
- Zijiao Yang
- West China School of Medicine, Sichuan University, Chengdu, 610000, China
- Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Xia Jiang
- West China School of Medicine, Sichuan University, Chengdu, 610000, China.
- Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610000, China.
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24
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Mangieri CW, Valenzuela CD, Strode MA, Erali RA, Shen P, Howerton R, Clark CJ. Effect of preoperative liver-directed therapy prior to hepatic resection. Am J Surg 2023; 225:703-708. [PMID: 36307334 DOI: 10.1016/j.amjsurg.2022.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 09/27/2022] [Accepted: 10/11/2022] [Indexed: 12/07/2022]
Abstract
INTRODUCTION Hepatobiliary malignancies present with advanced disease precluding upfront resection. Liver-directed therapy (LDT), particularly Y-90 radioembolization and transarterial chemoembolization (TACE), has become increasingly utilized to facilitate attempt at oncologic resection. However, the safety profile of preoperative LDT is limited. METHODS Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2014-2016. Primary objective was evaluation of outcomes between preoperative LDT cases and those that received upfront resection. RESULTS A total of 8923 cases met selection criteria. 192 cases (2.15%) received either Y-90 or TACE prior to hepatectomy. Multivariate analysis for all study patients revealed preoperative LDT significantly increased the risk of perioperative transfusion (OR 2.19, 95% CI 1.445-3.328, P < 0.0001), sepsis (OR 2.21, 95% CI 1.104-4.411, P = 0.022), and liver failure (OR 2.72, 95% CI 1.562-4.747, P < 0.0001). Subgroup analysis found for primary hepatobiliary malignancies LDT only increased the risk for liver failure. While for secondary hepatic tumors LDT significantly increased perioperative transfusion, sepsis, cardiac failure, renal failure, liver failure, and mortality. The complication profile also significantly increased with advanced T stage. Conversely, on propensity score matching preoperative LDT did not significantly increase perioperative complications. CONCLUSION Preoperative LDT has the potential to convert inoperable hepatic tumors into resectable disease but there is a general increased risk for significant postoperative complications, most notable liver failure. However, on controlled analysis preoperative LDT does not increase perioperative complications and should not be considered a contraindication to resection.
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Affiliation(s)
- Christopher W Mangieri
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States.
| | - Cristian D Valenzuela
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States
| | - Matthew A Strode
- Womack Army Medical Center, Department of General Surgery, United States
| | - Richard A Erali
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States
| | - Perry Shen
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States
| | - Russell Howerton
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States
| | - Clancy J Clark
- Wake Forest Baptist Health Medical Center, Division of Surgical Oncology, United States
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25
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Zhang J, Huang Q, Yang Y, Zhang J, Fang X, Yang Y, Liang H, Wang W, Wang Y. A novel prognostic system combining carbonic anhydrase II and preoperative CA19-9 for intrahepatic cholangiocarcinoma after curative resection. Cancer 2023; 129:1030-1040. [PMID: 36625486 DOI: 10.1002/cncr.34639] [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: 08/20/2022] [Revised: 12/09/2022] [Accepted: 12/10/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND The role of carbonic anhydrase II (CAII) in intrahepatic cholangiocarcinoma (ICC) was investigated and a novel prognostic system combining CAII and preoperative carbohydrate antigen 19-9 (CA19-9) was established to predict the survival of patients with ICC after curative resection. METHODS A total of 110 patients who underwent curative-intent resection for ICC between 2012 and 2020 were retrospectively analyzed. CAII in tumor and peritumor regions was examined by immunohistochemistry, and the relationships between clinicopathological factors and the prognostic value of CAII and CA19-9 were analyzed. RESULTS CAII was frequently downregulated in ICC tissues (p < .001). Multivariate analyses indicated that showed that both low CAII expression level and preoperative CA19-9 ≥236 U/ml were independent risk factors for overall survival (OS) and recurrence-free survival (RFS) in patients with ICC after radical resection. Survival analysis revealed that patients with high CAII and low CA19-9 were significantly associated with a better OS and RFS (p < .001). The time-dependent receiver operating characteristic curves showed that CAII + CA19-9 had better prognostic predictive ability than CAII or CA19-9 alone. The nomogram constructed on independent factors including T stage, lymph node metastasis, CA19-9 (continuous variable), and CAII achieved C-indexes of 0.754 (95% CI, 0.701-0.807) and 0.730 (0.674-0.785) for OS and RFS, respectively. The calibration curve revealed acceptable agreement between actual and predicted OS and RFS. CONCLUSIONS The combination of CAII and preoperative CA19-9 is a novel and useful prognostic tool for predicting the survival of patients with ICC after curative resection and guiding clinical decisions. PLAIN LANGUAGE SUMMARY Carbonic anhydrase II (CAII) was frequently downregulated in intrahepatic cholangiocarcinoma (ICC) tissues. Survival analysis revealed that CAII is a novel independent factor for prognosis in patients with ICC after curative resection. CAII could be a useful prognostic marker for patients with ICC after surgery. The combination of CAII and preoperative carbohydrate antigen 19-9 is a novel and useful prognostic tool for predicting the survival of patients with ICC after curative resection and guiding clinical decisions.
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Affiliation(s)
- Jiawei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Qiming Huang
- Department of Medical Imaging, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yi Yang
- Department of Radiology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiahui Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Xueting Fang
- Department of Pathology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yubin Yang
- Department of Pathology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Huifang Liang
- Department of Hepatobiliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yanjun Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
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26
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Choi WJ, Ivanics T, Gravely A, Gallinger S, Sapisochin G, O'Kane GM. Optimizing Circulating Tumour DNA Use in the Perioperative Setting for Intrahepatic Cholangiocarcinoma: Diagnosis, Screening, Minimal Residual Disease Detection and Treatment Response Monitoring. Ann Surg Oncol 2023; 30:3849-3863. [PMID: 36808320 DOI: 10.1245/s10434-023-13126-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/09/2023] [Indexed: 02/23/2023]
Abstract
In this review, we present the current evidence and future perspectives on the use of circulating tumour DNA (ctDNA) in the diagnosis, management and understanding the prognosis of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing surgery. Liquid biopsies or ctDNA maybe utilized to: (1) determine the molecular profile of the tumour and therefore guide the selection of molecular targeted therapy in the neoadjuvant setting, (2) form a surveillance tool for the detection of minimal residual disease or cancer recurrence after surgery, and (3) diagnose and screen for early iCCA detection in high-risk populations. The potential for ctDNA can be tumour-informed or -uninformed depending on the goals of its use. Future studies will require ctDNA extraction technique validations, with standardizations of both the platforms and the timing of ctDNA collections.
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Affiliation(s)
- Woo Jin Choi
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Tommy Ivanics
- Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Annabel Gravely
- HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Steven Gallinger
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. .,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada.
| | - Grainne M O'Kane
- Department of Medical Oncology, Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
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27
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Ebel S, Struck MF, van Boemmel F, Beeskow AB, Gößmann H, Denecke T. Chemosaturation of the Liver - an Update. ROFO-FORTSCHR RONTG 2023; 195:30-37. [PMID: 35977553 DOI: 10.1055/a-1858-3418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Percutaneous hepatic perfusion (CS-PHP) is a treatment option for primary and secondary liver neoplasms and subject of intensive research. This present article provides an overview of CS-PHP regarding patient safety, feasibility and effectiveness based on recent studies. METHOD We performed a PubMed search including the search terms chemosaturation, hepatic chemosaturation, percutaneous perfusion and melphalan. RESULTS AND CONCLUSION CS-PHP is a promising procedure for the treatment of uveal melanoma and cholangiocellular carcinoma. There are insufficient data regarding the effectiveness of CS-PHP with respect to other tumor entities. Since CS-PHP can be accompanied by multiple transient side effects and complications, close interdisciplinary cooperation is necessary. KEY POINTS · Chemosaturation of the liver is a safe procedure.. · CS-PHP is a potent therapy for hepatic metastatic ocular melanoma and cholangiocellular carcinoma.. · The procedure requires close interdisciplinary coordination.. · CS-PHP is a repeatable and thus long-term therapeutic option for some patients.. CITATION FORMAT · Ebel S, Struck MF, van Boemmel F et al. Chemosaturation of the Liver - an Update. Fortschr Röntgenstr 2023; 195: 30 - 37.
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Affiliation(s)
- Sebastian Ebel
- Klinik und Poliklinik für diagnostische und interventionelle Radiologie, Leipzig University, Leipzig, Germany
| | - Manuel Florian Struck
- Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Leipzig University, Leipzig, Germany
| | - Florian van Boemmel
- Klinik für Innere Medizin II, Sektion für Hepatologie, Leipzig University, Leipzig, Germany
| | - Anne Bettina Beeskow
- Klinik und Poliklinik für diagnostische und interventionelle Radiologie, Leipzig University, Leipzig, Germany
| | - Holger Gößmann
- Klinik und Poliklinik für diagnostische und interventionelle Radiologie, Leipzig University, Leipzig, Germany
| | - Timm Denecke
- Klinik und Poliklinik für diagnostische und interventionelle Radiologie, Leipzig University, Leipzig, Germany
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28
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Marcus R, Christopher W, Keller J, Nassoiy S, Chang SC, Goldfarb M, Wolf R, Jutric Z. Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade. Cancers (Basel) 2022; 14:4320. [PMID: 36077855 PMCID: PMC9454548 DOI: 10.3390/cancers14174320] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/19/2022] [Accepted: 08/31/2022] [Indexed: 11/16/2022] Open
Abstract
Limited evidence-based management guidelines for resectable intrahepatic cholangiocarcinoma (ICC) currently exist. Using a large population-based cancer registry; the utilization rates and outcomes for patients with clinical stages I-III ICC treated with neoadjuvant chemotherapy (NAT) in relation to other treatment strategies were investigated, as were the predictors of treatment regimen utilization. Oncologic outcomes were compared between treatment strategies. Amongst 2736 patients, chemotherapy utilization was low; however, NAT use increased from 4.3% to 7.2% (p = 0.011) over the study period. A higher clinical stage was predictive of the use of NAT, while higher pathologic stage and margin-positive resections were predictive of the use of adjuvant therapy (AT). For patients with more advanced disease, the receipt of NAT or AT was associated with significantly improved survival compared to surgery alone (cStage II, p = 0.040; cStage III, p = 0.003). Furthermore, patients receiving NAT were more likely to undergo margin-negative resections compared to those treated with AT (72.5% vs. 62.6%, p = 0.027), despite having higher-risk tumors. This analysis of treatment strategies for resectable ICC suggests a benefit for systemic therapy. Prospective and randomized studies evaluating the sequencing of treatments for patients with high-risk resectable ICC are needed.
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Affiliation(s)
- Rebecca Marcus
- Department of Surgical Oncology, Providence Saint John’s Cancer Institute, Santa Monica, CA 90404, USA
| | - Wade Christopher
- Department of Surgical Oncology, Providence Saint John’s Cancer Institute, Santa Monica, CA 90404, USA
| | - Jennifer Keller
- Department of Surgical Oncology, Providence Saint John’s Cancer Institute, Santa Monica, CA 90404, USA
| | - Sean Nassoiy
- Department of Surgical Oncology, Providence Saint John’s Cancer Institute, Santa Monica, CA 90404, USA
| | - Shu-Ching Chang
- Medical Data Research Center, Providence Saint Joseph Health, Portland, OR 97229, USA
| | - Melanie Goldfarb
- Department of Surgical Oncology, Providence Saint John’s Cancer Institute, Santa Monica, CA 90404, USA
| | - Ronald Wolf
- Division of Hepatobiliary and Pancreas Surgery, University of California Irvine, Orange, CA 92868, USA
| | - Zeljka Jutric
- Division of Hepatobiliary and Pancreas Surgery, University of California Irvine, Orange, CA 92868, USA
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29
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Choi WJ, Ivanics T, Claasen MPAW, Gallinger S, Hansen B, Sapisochin G. Is it safe to administer neoadjuvant chemotherapy to patients undergoing hepatectomy for intrahepatic cholangiocarcinoma? ACS-NSQIP propensity-matched analysis. HPB (Oxford) 2022; 24:1535-1542. [PMID: 35474005 DOI: 10.1016/j.hpb.2022.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/11/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The use of neoadjuvant chemotherapy (NAC) in patients with intrahepatic cholangiocarcinoma (iCCA) is increasing. The objective of this study was to compare the 30-day post-operative complications and length-of-stay (LOS) between patients undergoing hepatectomy for iCCA with and without NAC. METHODS A retrospective study was conducted using the ACS-NSQIP database queried from 2014 to 2018. Patients with NAC receipt were propensity-score matched into 1:3 ratio with controls using the greedy-matching algorithm and a caliper of 0.2. Logistic and Poisson regression models were used to estimate the effect sizes. RESULTS A total of 1508 patients who underwent hepatectomy for iCCA were included. 706 patients remained after matching and balance were achieved. The NAC group had 110 (60.1%) complications vs. 289 (55.3%) complications in the non-NAC group (p = 0.29). NAC was not associated with worse 30-day postoperative complications [OR 1.24, 95% CI: 0.87-1.76; p = 0.24]. Post-operative LOS in the NAC group was 8.56 days (mean, SD 7.4) vs. non-NAC group 9.27 days (mean, SD 8.41, p = 0.32). NAC was not associated with longer post-operative LOS [RR 0.93, 95% CI:0.80, 1.08; p = 0.32]. CONCLUSION NAC may be safely administered without increasing the risk of 30-day complications or post-operative hospital LOS.
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Affiliation(s)
- Woo Jin Choi
- University of Toronto, Department of General Surgery, Toronto, Canada; University Health Network, HPB Surgical Oncology, Toronto, Canada
| | - Tommy Ivanics
- University Health Network, HPB Surgical Oncology, Toronto, Canada; Department of Surgery, Henry Ford Hospital, Detroit, MI, USA; Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Marco P A W Claasen
- University Health Network, HPB Surgical Oncology, Toronto, Canada; Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Steven Gallinger
- University of Toronto, Department of General Surgery, Toronto, Canada; University Health Network, HPB Surgical Oncology, Toronto, Canada
| | - Bettina Hansen
- University Health Network, Center for Liver Disease, Toronto, Canada
| | - Gonzalo Sapisochin
- University of Toronto, Department of General Surgery, Toronto, Canada; University Health Network, HPB Surgical Oncology, Toronto, Canada.
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Patkar S, Gupta V, Khobragade K, Goel M. The reality of cholangiocarcinoma in India- real world data from a tertiary referral centre. HPB (Oxford) 2022; 24:1511-1518. [PMID: 35379594 DOI: 10.1016/j.hpb.2022.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 02/04/2022] [Accepted: 03/10/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cholangiocarcinomas (CCA) are rare tumours originating from bile duct. Due to their asymptomatic nature they are usually diagnosed when the disease is advanced. Little data exists with respect to their incidence and treatment outcomes in low and middle income countries. METHOD A retrospective analysis of a prospectively maintained database of all patients with perihilar (pCCA) and intrahepatic (iCCA) CCA registered between January 2012 and December 2018 was performed. RESULTS A total of 760 patients, 427 (56.2%) diagnosed with pCCA and 333 (43.8%) of iCCA were included. Patients with localised, locally advanced and metastatic disease in pCCA were 45.5%, 25.9%, 8.5% and that in iCCA were 22.1%, 10.1% and 67.7% respectively. Only 141 (43.9%, 57 - iCCA, 84 -pCCA) of the total 321 patients started on some definitive cancer directed therapy could complete the intended treatment. The overall curative resection rate for all patients of iCCA was 14.5% whereas for patients of pCCA it was only 10.5%. CONCLUSION More than half of CCA patients are not able to complete their intended treatment, being worse for pCCA as compared to iCCA. Early referral and centralisation of treatment for this complex disease might be the way forward to achieve optimal outcomes.
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Affiliation(s)
- Shraddha Patkar
- Hepatobiliary Division, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Vikas Gupta
- Hepatobiliary Division, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Krunal Khobragade
- Hepatobiliary Division, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai 400012, Maharashtra, India
| | - Mahesh Goel
- Hepatobiliary Division, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai 400012, Maharashtra, India.
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Nassar A, Tzedakis S, Sindayigaya R, Hobeika C, Marchese U, Veziant J, Codjia T, Beaufrère A, Dhote A, Strigalev M, Cauchy F, Fuks D. Factors of Early Recurrence After Resection for Intrahepatic Cholangiocarcinoma. World J Surg 2022; 46:2459-2467. [PMID: 35819486 DOI: 10.1007/s00268-022-06655-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Two-thirds of patients undergoing liver resection for intrahepatic cholangiocarcinoma experience recurrence after surgery. Our aim was to identify factors associated with early recurrence after resection for intrahepatic cholangiocarcinoma. METHODS Patients with intrahepatic cholangiocarcinoma undergoing curative intent resection (complete resection and lymphadenectomy) were included in two centers between 2005 and 2021 and were divided into three groups: early recurrence (< 12 months after resection), delayed recurrence (> 12 months), and no recurrence. Patients experiencing early (< 90 days) postoperative mortality were excluded. RESULTS Among 120 included patients, 44 (36.7%) experienced early recurrence, 24 (20.0%) experienced delayed recurrence, and 52 (43.3%) did not experience recurrence after a median follow-up of 59 months (IQR: 26-113). The median recurrence-free survival was 16 months (95% CI: 9.6-22.4). Median overall survival was 55 months (95% CI: 45.7-64.3), while it was 25 months for patients with early recurrence (p < 0.001). Patients with early recurrence had significantly larger tumors (59.1% of tumors > 70 mm in early vs. 58.3% in delayed vs. 26.9% in no recurrence group, p = 0.002), multiple lesions (65.9% vs. 29.2% vs. 11.5%, p < 0.001), and positive lymph nodes (N +) (38.6% vs. 37.5% vs. 11.5%, p = 0.005). In multivariable analysis, presence of multiple lesions (OR: 9.324; 95% CI: 3.051-28.489; p < 0.001) and positive lymph nodes (OR: 3.307. 95% CI: 1.001-11.011. p = 0.05) were associated with early recurrence. CONCLUSION Early recurrence after curative resection of intrahepatic cholangiocarcinoma is frequent and is associated with the presence of multiple lesions and positive lymph nodes, raising the question of surgery's futility in this context.
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Affiliation(s)
- Alexandra Nassar
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
| | - Stylianos Tzedakis
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Rémy Sindayigaya
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Christian Hobeika
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance publique-hôpitaux de Paris, University of Paris, Clichy, France
| | - Ugo Marchese
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Julie Veziant
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Tatiana Codjia
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance publique-hôpitaux de Paris, University of Paris, Clichy, France
| | - Aurélie Beaufrère
- Department of Pathology, Beaujon Hospital, Assistance publique-hôpitaux de Paris, University of Paris, Clichy, France
| | - Alix Dhote
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - Marie Strigalev
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
| | - François Cauchy
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance publique-hôpitaux de Paris, University of Paris, Clichy, France
| | - David Fuks
- Department of Hepatobiliary, Pancreatic and Endocrine Surgery, Cochin Hospital, Assistance publique-hôpitaux de Paris, University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France
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Xiao Y, Zhang B, Cloyd JM, Alaimo L, Xu G, Du S, Mao Y, Pawlik TM. Novel Drug Candidate Prediction for Intrahepatic Cholangiocarcinoma via Hub Gene Network Analysis and Connectivity Mapping. Cancers (Basel) 2022; 14:cancers14133284. [PMID: 35805055 PMCID: PMC9265136 DOI: 10.3390/cancers14133284] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/28/2022] [Accepted: 07/01/2022] [Indexed: 02/05/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy, and there is a need for effective systemic therapies. Gene expression profile-based analyses may allow for efficient screening of potential drug candidates to serve as novel therapeutics for patients with ICC. The RNA expression profile of ICC and normal biliary epithelial cells were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Function annotation and enrichment pathway analyses of the differentially expressed genes (DEGs) were finished using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A weighted gene co-expression network (WGCN) was constructed by WGCN analysis (WGCNA). Key genes from the DEGs and co-expression gene modules were analyzed to generate a protein-protein interaction (PPI) network. The association between the top 10 screened hub genes and the overall and disease-free survival of ICC patients was examined. The Connectivity Map (cMap) analysis was performed to identify possible drugs for ICC using hub genes. A total of 151 key genes were selected from the overlapping genes of 1287 GSE-DEGs, 8183 TCGA-DEGs and 1226 genes in the mixed modules. A total of 10 hub genes of interest (CTNNB1, SPP1, COL1A2, COL3A1, SMAD3, SRC, VCAN, PKLR, GART, MRPS5) were found analyzing protein-protein interaction. Using the cMap, candidate drugs screened with potential efficacy for ICC included three tyrosine kinase inhibitors (dasatinib, NVP-BHG712, tivantinib), two cannabinoid receptor agonists (palmitoylethanolamide, arachidonamide), two antibiotics (moxifloxacin, amoxicillin), one estrogen receptor agonist (levonorgestrel), one serine/threonine protein kinase inhibitor (MK-2206) and other small molecules. Key genes from network and PPI analysis allowed us to identify potential drugs for ICC. The identification of novel gene expression profiles and related drug screening may accelerate the identification of potential novel drug therapies for ICC.
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Affiliation(s)
- Yao Xiao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.X.); (B.Z.); (S.D.); (Y.M.)
| | - Baoluhe Zhang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.X.); (B.Z.); (S.D.); (Y.M.)
| | - Jordan M. Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; (J.M.C.); (L.A.)
| | - Laura Alaimo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; (J.M.C.); (L.A.)
| | - Gang Xu
- Department of Liver Surgery and Liver Transplant Center, West China Hospital of Sichuan University, Chengdu 610040, China;
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.X.); (B.Z.); (S.D.); (Y.M.)
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.X.); (B.Z.); (S.D.); (Y.M.)
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; (J.M.C.); (L.A.)
- Correspondence: ; Tel.: +1-614-293-8701
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Koustas E, Trifylli EM, Sarantis P, Papadopoulos N, Karapedi E, Aloizos G, Damaskos C, Garmpis N, Garmpi A, Papavassiliou KA, Karamouzis MV, Papavassiliou AG. Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer-Current Treatment Options and Future Perspectives. Int J Mol Sci 2022; 23:6664. [PMID: 35743107 PMCID: PMC9224428 DOI: 10.3390/ijms23126664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/12/2022] [Accepted: 06/14/2022] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.
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Affiliation(s)
- Evangelos Koustas
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece; (N.P.); (E.K.); (G.A.)
| | - Eleni-Myrto Trifylli
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece; (N.P.); (E.K.); (G.A.)
| | - Panagiotis Sarantis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
| | - Nikolaos Papadopoulos
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece; (N.P.); (E.K.); (G.A.)
| | - Eleni Karapedi
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece; (N.P.); (E.K.); (G.A.)
| | - Georgios Aloizos
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece; (N.P.); (E.K.); (G.A.)
| | - Christos Damaskos
- ‘N.S. Christeas’ Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
- Renal Transplantation Unit, ‘Laiko’ General Hospital, 11527 Athens, Greece
| | - Nikolaos Garmpis
- Second Department of Propaedeutic Surgery, ‘Laiko’ General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Anna Garmpi
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Kostas A. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
| | - Michalis V. Karamouzis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
| | - Athanasios G. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.K.); (E.-M.T.); (P.S.); (K.A.P.)
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Wang X, Liang P, Yu J, Yao JD, Fan FY, Yu X, Cheng ZG, Han ZY, Liu FY, Dou JP. Contrast-enhanced ultrasound features predict the prognosis of percutaneous microwave ablation of intrahepatic cholangiocarcinoma. Br J Radiol 2022; 95:20211379. [PMID: 35138914 PMCID: PMC10993967 DOI: 10.1259/bjr.20211379] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/13/2022] [Accepted: 01/19/2022] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To evaluate the prognostic effect of pre-operative contrast-enhanced ultrasound (CEUS) features on intrahepatic cholangiocarcinoma (ICC) after percutaneous microwave ablation (MWA). METHODS A total of ICC 29 patients (average age 56.34 ± 9.78 years old, 33~75 years old) underwent MWA from March 2012 to December 2020, with a total of 58 lesions (0.5-8.1 cm, mean diameter, 2.68 ± 1.59 cm), and their pre-operative CEUS images and clinical data were collected and reviewed. Survival rate, local progression rate, intra- and extrahepatic metastasis rate were evaluated. Uni- and multivariate analysis were used to analyze the prognostic factors affecting the survival of ICC patients with pre-operative CEUS features. RESULTS The median follow-up time after MWA was 18.43 months (4.17-93.13 months). 1-, 2-, and 3-year OS rates were 64.4%, 48.1% and 48.1%; 6-, 12-, 18-, 24-, 36-, 48-, and 60-month local progress and extrahepatic metastasis rates were 0.0%, 4.0%, 17.7%, 17.7%, 17.7%, 17.7%, 17.7% and 3.4%, 21.5%, 32.7%, 45.6%, 55.2%, 55.2% and 77.6%, respectively. Uni- and multivariate analysis showed that post-operative extrahepatic metastasis was an important factor for long-term survival of ICC patients after MWA (p = 0.006, 0.01), and Rim-enhancement feature of pre-operative CEUS was identified as an independent predictor of post-operative extrahepatic metastasis and long-term survival (p = 0.02, 0.02). CONCLUSION Rim-enhancement feature of pre-operative CEUS is a predictor high post-operative extrahepatic metastasis and poor prognosis through distant microvascular metastasis after MWA of ICC patients. ADVANCES IN KNOWLEDGE This study determined the important CEUS features of ICC and analyzed their impact on the prognosis of ICC patients after MWA, providing scientific guidance for better clinical treatment in the future.
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Affiliation(s)
- Xiaohui Wang
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
- Department of Ultrasound, The First Affiliated Hospital of
Zhengzhou University, Zhengzhou,
China
| | - Ping Liang
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Jun-dong Yao
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Fang-ying Fan
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Zhi-gang Cheng
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Zhi-yu Han
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Fang-yi Liu
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
| | - Jian-ping Dou
- Department of Interventional Ultrasound, The Fifth Medical
Center of PLA General Hospital,
Beijing, China
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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Rhee H, Choi SH, Park JH, Cho ES, Yeom SK, Park S, Han K, Lee SS, Park MS. Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma. Liver Int 2022; 42:930-941. [PMID: 35152534 DOI: 10.1111/liv.15196] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. METHODS We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n = 208) or validation set (n = 108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. RESULTS We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. CONCLUSIONS Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.
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Affiliation(s)
- Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine Seoul, Seoul, Republic of Korea
| | - Suk-Keu Yeom
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Kyunghwa Han
- Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, College of Medicine, Yonsei University, Seoul, South Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Krenzien F, Nevermann N, Krombholz A, Benzing C, Haber P, Fehrenbach U, Lurje G, Pelzer U, Pratschke J, Schmelzle M, Schöning W. Treatment of Intrahepatic Cholangiocarcinoma-A Multidisciplinary Approach. Cancers (Basel) 2022; 14:cancers14020362. [PMID: 35053523 PMCID: PMC8773654 DOI: 10.3390/cancers14020362] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/07/2022] [Accepted: 01/10/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary This review discusses multimodality treatment strategies for intrahepatic cholangiocarcinoma (iCC). Surgical resection remains the only potentially curative therapeutic option and the central cornerstone of treatment. Adjuvant systemic treatment will be recommended after resection or in the palliative setting. Increasing knowledge of phenotypic subclassification and molecular profiling allows investigation of targeted therapies as (neo-)adjuvant treatment. High-dose brachytherapy, internal radiation therapy, and transarterial chemoembolization are among the interventional treatment options being evaluated for unresectable iCC. Given the multiple options of multidisciplinary management, any treatment strategy should be discussed in a multidisciplinary tumor board and treatment should be directed by a specialized treatment center. Abstract Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use.
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Affiliation(s)
- Felix Krenzien
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
- Berlin Institute of Health (BIH), 13353 Berlin, Germany
| | - Nora Nevermann
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
- Correspondence:
| | - Alina Krombholz
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Christian Benzing
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Philipp Haber
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Uli Fehrenbach
- Clinic for Radiology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Georg Lurje
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Uwe Pelzer
- Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
| | - Wenzel Schöning
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; (F.K.); (A.K.); (C.B.); (P.H.); (G.L.); (J.P.); (M.S.); (W.S.)
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Spolverato G, Glavas D, Hewitt DB, Brown ZJ, Capelli G, Bergamo F, Rizzato MD, Pawlik TM. Advances in pharmacotherapy for cholangiocarcinoma: from conventional therapies to targeted drugs. Expert Opin Pharmacother 2021; 23:473-481. [PMID: 34964678 DOI: 10.1080/14656566.2021.2020250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Cholangiocarcinomas (CCA) are rare, highly invasive tumors often diagnosed at an advanced disease stage with an associated poor prognosis. Surgery represents the only chance for curative-intent treatment, but recurrence rates remain high. Neoadjuvant or adjuvant chemotherapy are options for patients with resectable CCA to increase recurrence-free survival and overall survival, while palliative chemotherapy represents the treatment for unresectable disease. Global efforts are currently focused on the development of novel more effective therapies. AREAS COVERED A review was conducted in August 2021 using the PubMed database with the following keywords: 'cholangiocarcinoma,' 'chemotherapy,' and 'therapy.' Manuscripts reporting on first- and second-line chemotherapy, neoadjuvant and adjuvant treatment regimens, and targeted therapies currently being tested or employed in the management of CCA were examined. EXPERT OPINION The prognosis of CCA is negatively affected by several factors including a lack of reliable biomarkers leading to delayed diagnoses, high inter- and intra-tumoral heterogeneity, and few effective chemotherapy regimens. In pursuit of more effective therapies, ongoing trials are testing both conventional and targeted drugs.
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Affiliation(s)
- Gaya Spolverato
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Dajana Glavas
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - D Brock Hewitt
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Giulia Capelli
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Francesca Bergamo
- Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy
| | - Mario Domenico Rizzato
- Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Hewitt DB, Brown ZJ, Pawlik TM. Surgical management of intrahepatic cholangiocarcinoma. Expert Rev Anticancer Ther 2021; 22:27-38. [PMID: 34730474 DOI: 10.1080/14737140.2022.1999809] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) incidence continues to rise worldwide, and overall survival remains poor. Complete surgical resection remains the only opportunity for cure in patients with ICC yet only one-third of patients present with resectable disease. AREAS COVERED While the low incidence rate of ICC hinders accrual of patients to large, randomized control trials, larger database and long-term institutional studies provide evidence to guide surgical management of ICC. These studies demonstrate feasibility, safety, and efficacy of aggressive surgical management in appropriately selected patients with ICC. Recent advances in the management of ICC, with a focus on surgical considerations, are reviewed. EXPERT OPINION Historically, little progress has been made in the management of ICC with stagnant mortality rates and poor long-term outcomes. However, regionalization of care to centers with experienced multidisciplinary teams, advances in minimally invasive surgical techniques, discovery and development of targeted and immunotherapy agents, and combination locoregional and systemic therapies offer signs of progress in the management of ICC.
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Affiliation(s)
- D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Serifis N, Tsilimigras DI, Cloonan DJ, Pawlik TM. Challenges and Opportunities for Treating Intrahepatic Cholangiocarcinoma. Hepat Med 2021; 13:93-104. [PMID: 34754247 PMCID: PMC8572023 DOI: 10.2147/hmer.s278136] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/22/2021] [Indexed: 12/29/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.
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Affiliation(s)
- Nikolaos Serifis
- Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA
| | | | - Daniel J Cloonan
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Zhang Z, Zhang W, Wang H, Hu B, Wang Z, Lu S. Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report. Front Immunol 2021; 12:744571. [PMID: 34603331 PMCID: PMC8484748 DOI: 10.3389/fimmu.2021.744571] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 09/06/2021] [Indexed: 01/05/2023] Open
Abstract
Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient’s survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Ze Zhang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China.,Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.,Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.,Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.,Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.,Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Hongguang Wang
- Department of Hepatobiliary Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Bingyang Hu
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.,Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.,Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Zhanbo Wang
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.,Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.,Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
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Zane KE, Cloyd JM, Mumtaz KS, Wadhwa V, Makary MS. Metastatic disease to the liver: Locoregional therapy strategies and outcomes. World J Clin Oncol 2021; 12:725-745. [PMID: 34631439 PMCID: PMC8479345 DOI: 10.5306/wjco.v12.i9.725] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/14/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.
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Affiliation(s)
- Kylie E Zane
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Khalid S Mumtaz
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Vibhor Wadhwa
- Department of Radiology, Weill Cornell Medical Center, New York City, NY 10065, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Cloyd JM, Pawlik TM. Trends in the use of adjuvant therapy for resected intrahepatic cholangiocarcinoma: getting ahead of the data. Hepatobiliary Surg Nutr 2021; 10:515-517. [PMID: 34430532 DOI: 10.21037/hbsn-2021-12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 05/17/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Lang H, Baumgart J, Heinrich S, Huber T, Heuft LK, Margies R, Mittler J, Hahn F, Gerber TS, Foerster F, Weinmann A, Marquardt JU, Kloeckner R, Straub BK, Bartsch F. Liver Resection for Intrahepatic Cholangiocarcinoma-Single-Center Experience with 286 Patients Undergoing Surgical Exploration over a Thirteen Year Period. J Clin Med 2021; 10:jcm10163559. [PMID: 34441855 PMCID: PMC8396970 DOI: 10.3390/jcm10163559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/05/2021] [Accepted: 08/10/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Intrahepatic cholangiocarcinoma (iCCA) accounts for about 10% of primary liver cancer. Surgery is the only potentially curative treatment. We report on our current series of 229 consecutive hepatic resections for iCCA, which is one of the largest Western single-center series published so far. Methods: Between January 2008 to December 2020, a total of 286 patients underwent 307 surgical explorations for intended liver resection of iCCA at our department. Data were analyzed with regard to (1) preoperative treatment of tumor, (2) operative details, (3) perioperative morbidity and mortality, (4) histopathology, (5) outcome measured by tumor recurrence, treatment of recurrence and survival and (6) prognostic factors for overall and disease-free survival. Results: the resectability rate was 74.6% (229/307). In total, 202 primary liver resections, 21 repeated, 5 re-repeated, and 1 re-re-repeated liver resections were performed. In primary liver resections there were 77% (155/202) major hepatectomies. In 39/202 (20%) of patients additional hepatic wedge resections and in 87/202 (43%) patients additional 119 other surgical procedures were performed next to hepatectomy. Surgical radicality in first liver resections was 166 R0-, 33 R1- and 1 R2-resection. Following the first liver resection, the calculated 1-, 3- and 5-year-survival is 80%, 39%, and 22% with a median survival of 25.8 months. Until the completion of data acquisition, tumors recurred in 123/202 (60.9%) patients after a median of 7.5 months (range 1–87.2 months) after resection. A multivariate cox regression revealed tumor size (p < 0.001), T stage (p < 0.001) and N stage (p = 0.003) as independent predictors for overall survival. N stage (p = 0.040), preoperative therapy (p = 0.005), T stage (p = 0.004), tumor size (p = 0.002) and M stage (p = 0.001) were independent predictors for recurrence-free survival. Conclusions: For complete surgical removal, often extended liver resection in combination with complex vascular or biliary reconstruction is required. However, despite aggressive surgery, tumor recurrence is frequent and long-term oncological results are poor. This indicated that surgery alone is unlikely to make great strides in improving prognosis of patients with iCCA, instead clearly suggesting that liver resection should be incorporated in multimodal treatment concepts.
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Affiliation(s)
- Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
- Correspondence: ; Tel.: +49-61-3117-7291
| | - Janine Baumgart
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Stefan Heinrich
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Tobias Huber
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Lisa-Katharina Heuft
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Rabea Margies
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Jens Mittler
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (F.H.); (R.K.)
| | - Tiemo S. Gerber
- Department of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (T.S.G.); (B.K.S.)
| | - Friedrich Foerster
- 1st Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (F.F.); (A.W.)
| | - Arndt Weinmann
- 1st Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (F.F.); (A.W.)
| | - Jens U. Marquardt
- 1st Department of Medicine, University Medical Centre Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany;
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (F.H.); (R.K.)
| | - Beate K. Straub
- Department of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (T.S.G.); (B.K.S.)
| | - Fabian Bartsch
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany; (J.B.); (S.H.); (T.H.); (L.-K.H.); (R.M.); (J.M.); (F.B.)
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Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data. J Clin Med 2021; 10:jcm10132745. [PMID: 34206469 PMCID: PMC8269152 DOI: 10.3390/jcm10132745] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/16/2021] [Accepted: 06/19/2021] [Indexed: 01/13/2023] Open
Abstract
Background: Syndecan-1 (CD138; SDC1) is a heparan sulfate proteoglycan that has been attributed a key role in cancer progression in ductal adenocarcinoma of the pancreas. We therefore aimed to investigate the role of syndecan-1 in cholangiocarcinoma. Methods: We analyzed syndecan-1 expression in a large, clinicopathologically well-characterized collective of 154 intrahepatic cholangiocarcinoma, 221 extrahepatic cholangiocarcinomas, and 95 gallbladder carcinomas as well as respective normal tissues and precursor lesions by immunohistochemistry with digital image analysis and correlated with recurrence-free survival and prognostic markers. Furthermore, we conducted an analysis of cancer genes in the cholangiocarcinoma cohort of The Cancer Genome Atlas (TCGA). Results: During cholangiocarcinogenesis, syndecan-1-expression decreased when compared to normal bile ducts and biliary intraepithelial neoplasia; however, syndecan-1 levels were found to be elevated in lymph node metastases. In the TCGA cohort, high mRNA SDC1 levels were associated with poor prognosis in intrahepatic cholangiocarcinoma. However, in our large cohort, the immunohistochemical syndecan-1 expression did not significantly correlate with recurrence-free survival. Conclusions: Syndecan-1 was found to be downregulated during cholangiocarcinogenesis, yet we could not show significant effects on prognosis on protein level. Further analyses are needed to further depict its specific role.
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Yin L, Zhao S, Zhu H, Ji G, Zhang X. Primary tumor resection improves survival in patients with multifocal intrahepatic cholangiocarcinoma based on a population study. Sci Rep 2021; 11:12166. [PMID: 34108604 PMCID: PMC8190174 DOI: 10.1038/s41598-021-91823-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 05/31/2021] [Indexed: 12/21/2022] Open
Abstract
The purpose of our study was to evaluate the effect of surgery on the survival and prognosis of patients with multifocal intrahepatic cholangiocarcinoma (ICCA). Patients with multifocal ICCA were selected from the SEER (Surveillance, Epidemiology, and End Results) database between 2010 and 2016. Kaplan–Meier analyses and log-rank tests were used to evaluate the difference in survival between the surgery group and the non-surgery group. We applied the Cox proportional hazards regression model to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). In total, 580 patients were enrolled in our study, including 151 patients who underwent surgery and 429 patients who did not. The median survival time of surgical patients was longer than non-surgical patients (OS: 25 months vs. 8 months, p < 0.001; CSS: 40 months vs. 25 months, p < 0.001). Similarly, the 5-year survival rate in the surgery group was significantly higher than those in the non-surgery group (5-year OS rate: 12.91% vs. 0%; p < 0.001; 5-year CSS rate:26.91% vs. 0%; p < 0.001). Multivariate Cox analysis showed that the OS (HR:0.299, 95% CI: 0.229–0.390, p < 0.001) and CSS (HR:0.305, 95% CI:0.222–0.419, p < 0.001) of patients undergoing surgical resection were significantly improved. Meanwhile, after propensity score matching (PSM) of the original data, we come to the same conclusion.
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Affiliation(s)
- Linlin Yin
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Si Zhao
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Hanlong Zhu
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Guozhong Ji
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
| | - Xiuhua Zhang
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
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Panayotova G, Guerra J, Guarrera JV, Lunsford KE. The Role of Surgical Resection and Liver Transplantation for the Treatment of Intrahepatic Cholangiocarcinoma. J Clin Med 2021; 10:2428. [PMID: 34070772 PMCID: PMC8199311 DOI: 10.3390/jcm10112428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 05/28/2021] [Indexed: 12/17/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a rare and complex malignancy of the biliary epithelium. Due to its silent presentation, patients are frequently diagnosed late in their disease course, resulting in poor overall survival. Advances in molecular profiling and targeted therapies have improved medical management, but long-term survival is rarely seen with medical therapy alone. Surgical resection offers a survival advantage, but negative oncologic margins are difficult to achieve, recurrence rates are high, and the need for adequate future liver remnant limits the extent of resection. Advances in neoadjuvant and adjuvant treatments have broadened patient treatment options, and these agents are undergoing active investigation, especially in the setting of advanced, initially unresectable disease. For those who are not able to undergo resection, liver transplantation is emerging as a potential curative therapy in certain cases. Patient selection, favorable tumor biology, and a protocolized, multidisciplinary approach are ultimately necessary for best patient outcomes. This review will discuss the current surgical management of locally advanced, liver-limited intrahepatic cholangiocarcinoma as well as the role of liver transplantation for select patients with background liver disease.
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Affiliation(s)
| | | | | | - Keri E. Lunsford
- Rutgers New Jersey Medical School, Department of Surgery, Division of Transplant and HPB Surgery, Newark, NJ 07103, USA; (G.P.); (J.G.); (J.V.G.)
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Kodali S, Shetty A, Shekhar S, Victor DW, Ghobrial RM. Management of Intrahepatic Cholangiocarcinoma. J Clin Med 2021; 10:jcm10112368. [PMID: 34072277 PMCID: PMC8198953 DOI: 10.3390/jcm10112368] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/20/2021] [Accepted: 05/22/2021] [Indexed: 01/04/2023] Open
Abstract
Cholangiocarcinoma is a tumor that arises as a result of differentiation of the cholangiocytes and can develop from anywhere in the biliary tree. Subtypes of cholangiocarcinoma are differentiated based on their location in the biliary tree. If diagnosed early these can be resected, but most cases of intrahepatic cholangiocarcinoma present late in the disease course where surgical resection is not an option. In these patients who are poor candidates for resection, a combination of chemotherapy, locoregional therapies like ablation, transarterial chemo and radioembolization, and in very advanced and metastatic disease, external radiation are the available options. These modalities can improve overall disease-free and progression-free survival chances. In this review, we will discuss the risk factors and clinical presentation of intrahepatic cholangiocarcinoma, diagnosis, available therapeutic options, and future directions for management options.
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Affiliation(s)
- Sudha Kodali
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA; (S.K.); (A.S.); (R.M.G.)
- Houston Methodist Research Institute, Houston, TX 77030, USA
| | - Akshay Shetty
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA; (S.K.); (A.S.); (R.M.G.)
- Houston Methodist Research Institute, Houston, TX 77030, USA
| | - Soumya Shekhar
- Texas A&M College of Medicine, Houston Campus, Houston, TX 77030, USA;
| | - David W. Victor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA; (S.K.); (A.S.); (R.M.G.)
- Houston Methodist Research Institute, Houston, TX 77030, USA
- Correspondence:
| | - Rafik M. Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA; (S.K.); (A.S.); (R.M.G.)
- Houston Methodist Research Institute, Houston, TX 77030, USA
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Lang H. Should all intrahepatic cholangiocarcinomas receive neoadjuvant chemotherapy before resection? Br J Surg 2021; 108:598-599. [PMID: 33723597 DOI: 10.1093/bjs/znab077] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/08/2021] [Indexed: 12/17/2022]
Affiliation(s)
- H Lang
- Department of General, Visceral and Transplant Surgery, University Medical Centre of Johannes Gutenberg-University Mainz, Mainz, Germany
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Beal EW, Cloyd JM, Pawlik TM. Surgical Treatment of Intrahepatic Cholangiocarcinoma: Current and Emerging Principles. J Clin Med 2020; 10:E104. [PMID: 33396821 PMCID: PMC7796337 DOI: 10.3390/jcm10010104] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 12/22/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare, aggressive cancer of the biliary tract. It often presents with locally advanced or metastatic disease, but for patients with early-stage disease, surgical resection with negative margins and portahepatis lymphadenectomy is the standard of care. Recent advancements in ICC include refinement of staging, improvement in liver-directed therapies, clarification of the role of adjuvant therapy based on new randomized controlled trials, and advances in minimally invasive liver surgery. In addition, improvements in neoadjuvant strategies and surgical techniques have enabled expanded surgical indications and reduced surgical morbidity and mortality. However, recurrence rates remain high and more effective systemic therapies are still necessary to improve recurrence-free and overall survival. In this review, we focus on current and emerging surgical principals for the management of ICC including preoperative evaluation, current indications for surgery, strategies for future liver remnant augmentation, technical principles, and the role of neoadjuvant and adjuvant therapies.
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Affiliation(s)
| | | | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH 43201, USA; (E.W.B.); (J.M.C.)
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