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He YG, Zhang LY, Li J, Wang Z, Zhao CY, Zheng L, Huang XB. Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids: A case report. World J Gastrointest Oncol 2024; 16:4274-4280. [PMID: 39473955 PMCID: PMC11514667 DOI: 10.4251/wjgo.v16.i10.4274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 08/20/2024] [Accepted: 08/28/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Patient-derived organoids (PDOs) have been demonstrated to predict the response to drugs in multiple cancer types. However, it remains unclear about its application in cholangiocarcinoma. CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months. According to relevant examinations, she was diagnosed as perihilar cholangiocarcinoma (pCCA) with intrahepatic metastasis and perihilar lymphatic metastasis. After multidisciplinary team discussion, percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction, and puncture biopsy was conducted to confirm the pathological diagnosis. Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib, but the levels of tumor markers including alpha fetal protein, carcinoembryonic antigen, carbohydrate antigen 15-3 and cancer antigen 125 were still raised. The PDO for drug screening showed sensitive to gemcitabine and cisplatin. Accordingly, the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib. After 4 cycles of treatment, the tumor was assessed resectable, and radical surgical resection was performed successfully. One year after surgery, the patient was still alive, and no recurrence or occurred. CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA, promoting conversion therapy and improving the prognosis.
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Affiliation(s)
- Yong-Gang He
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
| | - Ling-Yu Zhang
- School of Clinical Oncology, Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, Fujian Province, China
- Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, Fujian Province, China
| | - Jing Li
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
| | - Zheng Wang
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
| | - Chong-Yu Zhao
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
| | - Lu Zheng
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
| | - Xiao-Bing Huang
- Department of Hepatobiliary, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
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Yee EJ, Ziogas IA, Moris DP, Torphy RJ, Mungo B, Gleisner AL, Del Chiaro M, Schulick RD. Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review. Ann Surg Oncol 2024; 31:6504-6513. [PMID: 38972927 DOI: 10.1245/s10434-024-15567-4] [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: 02/23/2024] [Accepted: 05/22/2024] [Indexed: 07/09/2024]
Abstract
Resectable cholangiocarcinoma (CCA) arising from the middle of the extrahepatic biliary tree has historically been classified as perihilar or distal CCA, depending on the operation contemplated or performed, namely the associated hepatectomy or pancreaticoduodenectomy, respectively. Segmental bile duct resection is a less invasive alternative for select patients harboring true middle extrahepatic CCA (MCC). A small, yet growing body of literature has emerged detailing institutional experiences with bile duct resection versus pancreaticoduodenectomy or concomitant hepatectomy for MCC. Herein, we provide a brief overview of the epidemiology, preoperative evaluation, and emerging systemic therapies for MCC, and narratively review the existing work comparing segmental resection with pancreaticoduodenectomy or less commonly, hepatectomy, for MCC, with emphasis on the surgical management and oncologic implications of the approach used.
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Affiliation(s)
- Elliott J Yee
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Ioannis A Ziogas
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Dimitrios P Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Robert J Torphy
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Benedetto Mungo
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Ana L Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Cancer Center, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
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3
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Hall LA, Loader D, Gouveia S, Burak M, Halle-Smith J, Labib P, Alarabiyat M, Marudanayagam R, Dasari BV, Roberts KJ, Raza SS, Papamichail M, Bartlett DC, Sutcliffe RP, Chatzizacharias NA. Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy. World J Gastrointest Surg 2024; 16:2689-2701. [PMID: 39220089 PMCID: PMC11362928 DOI: 10.4240/wjgs.v16.i8.2689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 05/28/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse. AIM To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement. METHODS A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected. RESULTS Twelve studies were included. The definition of "unresectable" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively. CONCLUSION Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network® criteria for pancreatic ductal adenocarcinoma.
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Affiliation(s)
- Lewis A Hall
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Duncan Loader
- College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Santiago Gouveia
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Marta Burak
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - James Halle-Smith
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Peter Labib
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Moath Alarabiyat
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Ravi Marudanayagam
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Bobby V Dasari
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Syed S Raza
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Michail Papamichail
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Robert P Sutcliffe
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
- Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
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Esmail A, Badheeb M, Alnahar BW, Almiqlash B, Sakr Y, Al-Najjar E, Awas A, Alsayed M, Khasawneh B, Alkhulaifawi M, Alsaleh A, Abudayyeh A, Rayyan Y, Abdelrahim M. The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma. Pharmaceuticals (Basel) 2024; 17:910. [PMID: 39065760 PMCID: PMC11279608 DOI: 10.3390/ph17070910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06610, USA
| | | | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA;
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ali Awas
- Faculty of Medicine and Health Sciences, University of Science and Technology, Sanaa P.O. Box 15201-13064, Yemen
| | | | - Bayan Khasawneh
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | | | - Amneh Alsaleh
- Department of Medicine, Desert Regional Medical Center, Palm Springs, CA 92262, USA
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
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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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6
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Taghizadeh H, Dong Y, Gruenberger T, Prager GW. Perioperative and palliative systemic treatments for biliary tract cancer. Ther Adv Med Oncol 2024; 16:17588359241230756. [PMID: 38559612 PMCID: PMC10981863 DOI: 10.1177/17588359241230756] [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: 03/03/2023] [Accepted: 01/18/2024] [Indexed: 04/04/2024] Open
Abstract
Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established. The application of neoadjuvant therapy in locally advanced disease may be indicated, the routine use of systemic therapy prior to surgery for cholangiocarcinoma patients with an upfront resectable disease is less well established, but discussed and performed in selected cases. In advanced disease, only combination chemotherapy regimens have been demonstrated to achieve disease control in untreated patients. Molecular profiling of the tumor has demonstrated that many BTC might bear actionable targets, which might be addressed by biological treatments, thus improving the prognosis of the patients. Furthermore, the addition of the immunotherapy to standard chemotherapy might improve the prognosis in a subset of patients. This review seeks to give a comprehensive overview about the role of neoadjuvant as well as palliative systemic treatment approaches and an outlook about novel systemic treatment concept in BTC.
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Affiliation(s)
- Hossein Taghizadeh
- Division of Oncology, Department of Internal Medicine I, University Hospital St. Pölten, St. Pölten, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
- Karl Landsteiner Institute for Oncology and Nephrology, St. Pölten, Austria
- Medical University of Vienna, Center for Cancer Research, Vienna, Austria
- Medical University of Vienna, Department of Medicine I, Vienna, Austria
| | - Yawen Dong
- Department of Surgery, HPB Center, Health Network Vienna, Clinic Favoriten, Vienna, Austria
| | - Thomas Gruenberger
- Department of Surgery, HPB Center, Health Network Vienna, Clinic Favoriten, Vienna, Austria
| | - Gerald W. Prager
- Department of Medicine I, Medical University of Vienna, Comprehensive Cancer Center Vienna, Spitalgasse 23, Vienna AT1090, Austria
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7
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Wilbur HC, Soares HP, Azad NS. Neoadjuvant and adjuvant therapy for biliary tract cancer: Advances and limitations. Hepatology 2024:01515467-990000000-00725. [PMID: 38266282 DOI: 10.1097/hep.0000000000000760] [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: 09/06/2023] [Accepted: 12/31/2023] [Indexed: 01/26/2024]
Abstract
Biliary tract cancers (BTC) are a rare and aggressive consortium of malignancies, consisting of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma. While most patients present with metastatic disease, a minority of patients with BTC are eligible for curative surgical resection at the time of presentation. However, these patients have poor 5-year overall survival rates and high rates of recurrence, necessitating the improvement of the neoadjuvant and adjuvant treatment of BTC. In this review, we assess the neoadjuvant and adjuvant clinical trials for the treatment of BTC and discuss the challenges and limitations of clinical trials, as well as future directions for the treatment of BTC.
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Affiliation(s)
- H Catherine Wilbur
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Heloisa P Soares
- Division of Oncology, Department of Internal Medicine Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA
| | - Nilofer S Azad
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
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8
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Padmanaban V, Ruff SM, Pawlik TM. Multi-Disciplinary Care of Hilar Cholangiocarcinoma: Review of Guidelines and Recent Advancements. Cancers (Basel) 2023; 16:30. [PMID: 38201457 PMCID: PMC10778096 DOI: 10.3390/cancers16010030] [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: 11/21/2023] [Revised: 12/09/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a rare malignancy of the intrahepatic and extrahepatic biliary ducts. CCA is primarily defined by its anatomic location: intrahepatic cholangiocarcinoma versus extrahepatic cholangiocarcinoma. Hilar cholangiocarcinoma (HC) is a subtype of extrahepatic cholangiocarcinoma that arises from the common hepatic bile duct and can extend to the right and/or left hepatic bile ducts. Upfront surgery with adjuvant capecitabine is the standard of care for patients who present with early disease and the only curative therapy. Unfortunately, most patients present with locally advanced or metastatic disease and must rely on systemic therapy as their primary treatment. However, even with current systemic therapy, survival is still poor. As such, research is focused on developing targeted therapies and multimodal strategies to improve overall prognosis. This review discusses the work-up and management of HC focused on the most up-to-date literature and ongoing clinical trials.
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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 Comprehensive Cancer Center, Columbus, OH 43210, USA; (V.P.)
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9
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Abe Y, Itano O, Takemura Y, Minagawa T, Ojima H, Shinoda M, Kitago M, Obara H, Shigematsu N, Kitagawa Y. Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02). Ann Gastroenterol Surg 2023; 7:808-818. [PMID: 37663959 PMCID: PMC10472356 DOI: 10.1002/ags3.12682] [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: 01/25/2023] [Revised: 04/01/2023] [Accepted: 04/11/2023] [Indexed: 09/05/2023] Open
Abstract
Aim Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study. Methods Patients diagnosed with resectable stage II-IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S-1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one-step lower than the maximum-tolerated dose, which was defined when dose-limiting toxicity was observed in three or more of the six patients. Results Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose-limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum-tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery. Conclusion We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.
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Affiliation(s)
- Yuta Abe
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Osamu Itano
- Department of SurgeryKeio University School of MedicineTokyoJapan
- Department of Hepato‐Biliary‐Pancreatic and Gastrointestinal SurgeryInternational University of Health and Welfare School of MedicineChibaJapan
| | - Yusuke Takemura
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Takuya Minagawa
- Department of Hepato‐Biliary‐Pancreatic and Gastrointestinal SurgeryInternational University of Health and Welfare School of MedicineChibaJapan
| | - Hidenori Ojima
- Department of PathologyKeio University School of MedicineTokyoJapan
| | - Masahiro Shinoda
- Department of SurgeryKeio University School of MedicineTokyoJapan
- Digestive Disease CenterMita Hospital, International University of Health and WelfareTokyoJapan
| | - Minoru Kitago
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Hideaki Obara
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | | | - Yuko Kitagawa
- Department of SurgeryKeio University School of MedicineTokyoJapan
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10
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Takayama H, Kobayashi S, Gotoh K, Sasaki K, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Asaoka T, Noda T, Wada H, Takahashi H, Tanemura M, Doki Y, Eguchi H. SPARC accelerates biliary tract cancer progression through CTGF-mediated tumor-stroma interactions: SPARC as a prognostic marker of survival after neoadjuvant therapy. J Cancer Res Clin Oncol 2023; 149:10935-10950. [PMID: 37330435 DOI: 10.1007/s00432-023-04835-7] [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: 01/17/2023] [Accepted: 05/02/2023] [Indexed: 06/19/2023]
Abstract
PURPOSE In biliary tract cancer (BTC), malignancy is strongest at the invasion front. To improve the BTC prognosis, the invasion front should be controlled. We evaluated tumor-stroma crosstalk at the tumor center and at the invasion front of BTC lesions. We investigated the expression of SPARC, a marker of cancer-associated fibroblasts, and determined its ability to predict BTC prognosis after neoadjuvant chemoradiotherapy (NAC-RT). METHODS We performed immunohistochemistry to evaluate SPARC expression in resected specimens from patients that underwent BTC surgery. We established highly invasive (HI) clones in two BTC cell lines (NOZ, CCLP1), and performed mRNA microarrays to compare gene expression in parental and HI cells. RESULTS Among 92 specimens, stromal SPARC expression was higher at the invasion front than at the lesion center (p = 0.014). Among 50 specimens from patients treated with surgery alone, high stromal SPARC expression at the invasion front was associated with a poor prognosis (recurrence-free survival: p = 0.033; overall survival: p = 0.017). Coculturing fibroblasts with NOZ-HI cells upregulated fibroblast SPARC expression. mRNA microarrays showed that connective tissue growth factor (CTGF) was upregulated in NOZ-HI and CCLP1-HI cells. A CTGF knockdown suppressed cell invasion in NOZ-HI cells. Exogeneous CTGF upregulated SPARC expression in fibroblasts. SPARC expression at the invasion front was significantly lower after NAC-RT, compared to surgery alone (p = 0.003). CONCLUSION CTGF was associated with tumor-stroma crosstalk in BTC. CTGF activated stromal SPARC expression, which promoted tumor progression, particularly at the invasion front. SPARC expression at the invasion front after NAC-RT may serve as a prognosis predictor.
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Affiliation(s)
- Hirotoshi Takayama
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Rinku General Medical Center, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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11
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Bellefkih FZ, Benchakroun N, Lalya I, Amaoui B, El Kacemi H, Acharki A, El Hfid M, El Mazghi A, Chekrine T, Bouchbika Z, Jouhadi H, Sahraoui S, Tawfiq N, Michalet M. Radiotherapy in the management of rare gastrointestinal cancers: A systematic review. Cancer Radiother 2023; 27:622-637. [PMID: 37500390 DOI: 10.1016/j.canrad.2023.06.010] [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: 06/06/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 07/29/2023]
Abstract
The aim of this analysis is to assess radiotherapy's role and technical aspects in an array of rare gastrointestinal (GI) cancers for adult patients. Collection data pertaining to radiotherapy and digestive rare cancers were sourced from Medline, EMBASE, and Cochrane Library. Preoperative chemoradiotherapy improved outcomes for patients with esophageal undifferentiated carcinoma compared with esophageal salivary gland types of carcinomas. For rare gastric epithelial carcinoma, perioperative chemotherapy is the common treatment. Adjuvant chemoradiotherapy showed no benefice compared with adjuvant chemotherapy for duodenal adenocarcinoma. Small bowel sarcomas respond well to radiotherapy. By analogy to anal squamous cell carcinoma, exclusive chemoradiotherapy provided better outcomes for patients with rectal squamous cell carcinoma. For anal adenocarcinoma, neoadjuvant chemoradiotherapy, followed by radical surgery, was the most effective regimen. For pancreatic neuroendocrine tumors, chemoradiotherapy can be a suitable option as postoperative or exclusive for unresectable/borderline disease. The stereotactic body radiotherapy (SBRT) is a promising approach for hepatobiliary malignancy. Radiotherapy is a valuable option in gastrointestinal stromal tumors (GIST) for palliative intent, tyrosine kinase inhibitors (TKIs) resistant disease, and unresectable or residual disease. Involved field (IF) radiotherapy for digestive lymphoma provides good results, especially for gastric extranodal marginal zone lymphoma (MALT). In conclusion, radiotherapy is not an uncommon indication in this context. A multidisciplinary approach is needed for better management of digestive rare cancers.
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Affiliation(s)
- F Z Bellefkih
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco.
| | - N Benchakroun
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco; Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - I Lalya
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - B Amaoui
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - H El Kacemi
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - A Acharki
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - M El Hfid
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - A El Mazghi
- Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - T Chekrine
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - Z Bouchbika
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - H Jouhadi
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - S Sahraoui
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco; Association marocaine d'oncologie-radiothérapie (Aoram), Casablanca, Morocco
| | - N Tawfiq
- Department of Radiotherapy-Oncology, Ibn Rochd University Hospital, Hassan II University, Casablanca, Morocco
| | - M Michalet
- Service d'oncologie-radiothérapie, institut du cancer de Montpellier, Fédération d'oncologie-radiothérapie d'Occitanie Méditerranée (Forom), Montpellier, France
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12
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Clinical feasibility of curative surgery after nab-paclitaxel plus gemcitabine-cisplatin chemotherapy in patients with locally advanced cholangiocarcinoma. Surgery 2023; 173:280-288. [PMID: 36435652 DOI: 10.1016/j.surg.2022.09.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 08/25/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND This study was conducted to evaluate the clinical feasibility of nab-paclitaxel plus gemcitabine-cisplatin triplet chemotherapy in patients with locally advanced cholangiocarcinoma in real-world practice. METHODS We retrospectively reviewed patients with locally advanced cholangiocarcinoma who were treated with nab-paclitaxel plus gemcitabine-cisplatin between October 2019 and August 2021 at a single institution. The initial diagnosis of cholangiocarcinoma was histologically confirmed. RESULTS One hundred twenty-nine patients were included in this study. Among the patients with a measurable lesion (57.4%), the objective response rate and disease control were 60.8% and 91.9%, respectively. Seventy-seven patients (59.7%) were determined as resectable after triplet chemotherapy, but 73 (56.6%) underwent subsequent curative surgery. The major postoperative complication rate was 15.1%, and there were 2 postoperative mortalities (2.7%). There were 6 complete remission cases (8.2%) in the final pathology. The R0 resection was achieved in 67 patients (91.8%). Despite the initial locally advanced cholangiocarcinoma, a pathologic T stage of less than T2 was reported in 67 patients (91.8%). Fifty-two patients (71.2%) had no lymph node metastasis. Patients who underwent surgery after triplet chemotherapy had significantly higher 12-month overall survival (95.9% vs 76.8%; P < .001) than those treated with chemotherapy alone. CONCLUSION Nab-paclitaxel plus gemcitabine-cisplatin chemotherapy demonstrated a down-staging effect through a high response rate, indicating that this triplet chemotherapy is feasible as induction therapy in patients with locally advanced cholangiocarcinoma.
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13
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Sookprasert A, Wirasorn K, Chindaprasirt J, Watcharenwong P, Sanlung T, Putraveephong S. Systemic Treatment for Cholangiocarcinoma. Recent Results Cancer Res 2023; 219:223-244. [PMID: 37660335 DOI: 10.1007/978-3-031-35166-2_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Cholangiocarcinoma (CCA) is a diverse group of epithelial cancers that affect the biliary tree. The incidence of CCA is low in Western countries but significantly higher in endemic regions such as China and Thailand. Various risk factors contribute to the development of CCA. Recent studies have revealed molecular alterations in biliary tract cancers, providing insights into cholangiocarcinogenesis and potential targeted therapies. Surgical resection is the primary curative treatment for CCA. Adjuvant chemotherapy has been extensively studied, and some regimens have proven to be beneficial. Neoadjuvant chemotherapy has shown potential benefits in select cases, but its role remains controversial. In advanced stages, chemotherapy is the standard of care, and molecular profiling has identified potential targets such as FGFR, IDH1, HER2, and other tumor-agnostic therapies. Immunotherapy has demonstrated limited benefit in advanced CCA. This chapter provides an overview of the current evidence and ongoing research evaluating various chemotherapy regimens, targeted therapies, and immunotherapies across different stages of CCA.
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Affiliation(s)
- Aumkhae Sookprasert
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
| | - Kosin Wirasorn
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Jarin Chindaprasirt
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Piyakarn Watcharenwong
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Thanachai Sanlung
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Siraphong Putraveephong
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
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14
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Silver CM, Joung RH, Logan CD, Benson AB, Mahalingam D, D’Angelica MI, Bentrem DJ, Yang AD, Bilimoria KY, Merkow RP. Neoadjuvant therapy use and association with postoperative outcomes and overall survival in patients with extrahepatic cholangiocarcinoma. J Surg Oncol 2023; 127:90-98. [PMID: 36194064 PMCID: PMC9729397 DOI: 10.1002/jso.27112] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 09/18/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES Evidence for neoadjuvant therapy (NAT) in extrahepatic cholangiocarcinoma (eCCA) is limited. Our objectives were to: (1) characterize treatment trends, (2) identify factors associated with receipt of NAT, and (3) evaluate associations between NAT and postoperative outcomes. METHODS Retrospective cohort study of the National Cancer Database (2004-2017). Multivariable logistic regression assessed associations between NAT and postoperative outcomes. Stratified analysis evaluated differences between surgery first, neoadjuvant chemotherapy, and neoadjuvant chemoradiation (CRT). RESULTS Among 8040 patients, 417 (5.2%) received NAT. NAT increased during the study period 2.9%-8.4% (p < 0.001). Factors associated with receipt of NAT included age <50 (vs. >75, odds ratio [OR] 4.32, p < 0.001) and stage 3 disease (vs. 1, OR 1.68, p = 0.01). Compared with surgery first, patients who received NAT had higher odds of R0 resection (OR 1.49, p = 0.01) and lower 30-day mortality (OR 0.51, p = 0.04). On stratified analysis, neoadjuvant chemotherapy was not associated with differences in any outcomes. However, neoadjuvant CRT was associated with improvement in R0 resection (OR 3.52, <0.001) and median survival (47.8 vs. 25.3 months, log-rank < 0.001) compared to surgery first. CONCLUSIONS NAT, particularly neoadjuvant CRT, was associated with improved postoperative outcomes. These data suggest expanding the use of neoadjuvant CRT for eCCA.
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Affiliation(s)
- Casey M. Silver
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rachel H. Joung
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Charles D. Logan
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Al B. Benson
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
| | - Devalingam Mahalingam
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael I. D’Angelica
- Department of Surgery, Memorial Sloane Kettering Cancer Center, New York, New York, USA
| | - David J. Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Anthony D. Yang
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Karl Y. Bilimoria
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ryan P. Merkow
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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15
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Vatankhah F, Salimi N, Khalaji A, Baradaran B. Immune checkpoints and their promising prospect in cholangiocarcinoma treatment in combination with other therapeutic approaches. Int Immunopharmacol 2023; 114:109526. [PMID: 36481527 DOI: 10.1016/j.intimp.2022.109526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/21/2022] [Accepted: 11/27/2022] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma (CCA) is one of the malignant tumors that has shown rapid development in incidence and mortality in recent years. Like other types of cancer, patients with CCA experience alterations in the expression of immune checkpoints, indicating the importance of immune checkpoint inhibitors in treating CCA. The results of TCGA analysis in this study revealed a marginal difference in the expression of important immune checkpoints, Programmed cell death 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and their ligands in CCA samples compared to normal ones. This issue showed the importance of combination therapy in this cancer. This review considers CCA treatment and covers several therapeutic modalities or combined treatment strategies. We also cover the most recent developments in the field and outline the important areas of immune checkpoint molecules as prognostic variables and therapeutic targets in CCA.
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Affiliation(s)
- Fatemeh Vatankhah
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Salimi
- School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Amirreza Khalaji
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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16
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Adam MA, Glencer A, AlMasri S, Winters S, Bahary N, Singhi A, Lee KK, Paniccia A, Zureikat AH. Neoadjuvant Therapy Versus Upfront Resection for Nonpancreatic Periampullary Adenocarcinoma. Ann Surg Oncol 2023; 30:165-174. [PMID: 35925536 PMCID: PMC11186695 DOI: 10.1245/s10434-022-12257-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 05/30/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND In contrast to pancreatic ductal adenocarcinoma (PDAC), neoadjuvant therapy (NAT) for periampullary adenocarcinomas is not well studied, with data limited to single-institution retrospective reviews with small cohorts. We sought to compare outcomes of NAT versus upfront resection (UR) for non-PDAC periampullary adenocarcinomas. PATIENTS AND METHODS Using the National Cancer Database (NCDB), we identified patients who underwent surgery for extrahepatic cholangiocarcinoma, ampullary adenocarcinoma, or duodenal adenocarcinoma from 2006 to 2016. We compared outcomes between NAT versus UR groups for each tumor subtype with 1:3 propensity score matching. Cox regression was used to identify predictors of survival. RESULTS Among 7656 patients who underwent resection for non-PDAC periampullary adenocarcinoma, the proportion of patients who received NAT increased from 6 to 11% for cholangiocarcinoma (p < 0.01), 1 to 4% for ampullary adenocarcinoma (p = 0.01), and 5 to 8% for duodenal adenocarcinoma (p = 0.08). Length of stay, readmission, and 30-day mortality were comparable between NAT and UR. All tumor subtypes were downstaged following NAT (p < 0.01). The R0 resection rate was significantly higher in patients with extrahepatic cholangiocarcinoma who received NAT, and these patients had improved median overall survival (38 vs 26 months, p < 0.001). After adjustment for clinicopathologic factors and adjuvant chemotherapy, use of NAT was associated with improved survival in patients with cholangiocarcinoma [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.54-0.89, p = 0.004] but not duodenal or ampullary adenocarcinoma. The survival advantage for cholangiocarcinoma persisted after propensity matching. CONCLUSION This national cohort analysis suggests, for the first time, that neoadjuvant therapy is associated with improved survival in patients with extrahepatic cholangiocarcinoma.
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Affiliation(s)
- Mohamed Abdelgadir Adam
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, USA.
- Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
| | - Alexa Glencer
- Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Samer AlMasri
- UPMC Network Cancer Registry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Sharon Winters
- UPMC Network Cancer Registry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Nathan Bahary
- Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aatur Singhi
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kenneth K Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
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17
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Cremen S, Kelly ME, Gallagher TK. The role of neo-adjuvant therapy in cholangiocarcinoma: A systematic review. Front Oncol 2022; 12:975136. [PMID: 36568243 PMCID: PMC9779982 DOI: 10.3389/fonc.2022.975136] [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: 06/21/2022] [Accepted: 11/17/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Cholangiocarcinoma (CCA) is the most common malignancy affecting the biliary tree. The only curative treatment is surgical resection, aiming for negative margins (R0). For those who have locally advanced disease, which is borderline resectable, neoadjuvant chemoradiation presents an opportunity to reduce tumour size and allow for surgical resection. The aim of this review is to establish the role of neoadjuvant therapy in each subtype of CCA and establish its impact on survival. Methods Search terms such as 'neoadjuvant therapy' and 'cholangiocarcinoma' were searched on multiple databases, including Pubmed, Ovid and Embase. They were then reviewed separately by two reviewers for inclusion criteria. 978 studies were initially identified from the search strategy, with 21 being included in this review. Results 5,009 patients were included across 21 studies. 1,173 underwent neoadjuvant therapy, 3,818 had surgical resection alone. 359 patients received Gemcitabine based regimes, making it the most commonly utilised regimen for patients CCA and Biliary Tract Cancer (BTC). Data on tolerability of regimes was limited. All included papers were found to have low risk of bias when assessed using The Newcastle Ottawa Scale. Patients who underwent neoadjuvant therapy had a similar median overall survival compared to those who underwent upfront surgery (38.4 versus 35.1 months respectively). Pre-operative CA19-9, microvascular invasion, perineurial invasion and positive lymph nodes were of prognostic significance across BTC and CCA subtypes. Conclusion Neoadjuvant therapy and surgical resection is associated with improved patient outcomes and longer median overall survival compared to therapy and upfront surgery, however heterogeneity between research papers limited the ability to further analyse the significance of these results. Although initial studies are promising, further research is required in order to define suitable treatment protocols and tolerability of neoadjuvant regimes. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42020164781.
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Affiliation(s)
- Sinead Cremen
- Department of Hepatobiliary Surgery, St. Vincent’s University Hospital, Dublin, Ireland
| | - Michael E. Kelly
- Department of Surgery, Tallaght University Hospital, Tallaght, Dublin, Ireland
| | - Tom K. Gallagher
- Department of Hepatobiliary Surgery, St. Vincent’s University Hospital, Dublin, Ireland,*Correspondence: Tom K. Gallagher,
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18
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Woods E, Le D, Jakka BK, Manne A. Changing Landscape of Systemic Therapy in Biliary Tract Cancer. Cancers (Basel) 2022; 14:2137. [PMID: 35565266 PMCID: PMC9105885 DOI: 10.3390/cancers14092137] [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: 03/28/2022] [Revised: 04/17/2022] [Accepted: 04/22/2022] [Indexed: 12/19/2022] Open
Abstract
Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line. Newer targets and newer agents for established targets are being investigated, and this may change the BTC management landscape in the coming years from traditional CT to individualized therapy (TT) or ICI-centered combinations. The latter group may occupy major space in BTC management due to the paucity of targetable mutations and a greater toxicity profile.
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Affiliation(s)
- Edward Woods
- Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 432120, USA;
| | - Dat Le
- Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Institute at The Ohio State University, 460 W 10th Ave, Columbus, OH 43210, USA;
| | - Bharath Kumar Jakka
- Department of Internal Medicine, Baptist Medical Center South, Montgomery, AL 36116, USA;
| | - Ashish Manne
- Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
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19
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Wang N, Huang A, Kuang B, Xiao Y, Xiao Y, Ma H. Progress in Radiotherapy for Cholangiocarcinoma. Front Oncol 2022; 12:868034. [PMID: 35515132 PMCID: PMC9063097 DOI: 10.3389/fonc.2022.868034] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/23/2022] [Indexed: 12/30/2022] Open
Abstract
Cholangiocarcinoma (CCA) originates from the epithelium of the bile duct and is highly malignant with a poor prognosis. Radical resection is the only treatment option to completely cure primary CCA. Due to the insidious onset of CCA, most patients are already in an advanced stage at the time of the initial diagnosis and may lose the chance of radical surgery. Radiotherapy is an important method of local treatment, which plays a crucial role in preoperative neoadjuvant therapy, postoperative adjuvant therapy, and palliative treatment of locally advanced lesions. However, there is still no unified and clear recommendation on the timing, delineating the range of target area, and the radiotherapy dose for CCA. This article reviews recent clinical studies on CCA, including the timing of radiotherapy, delineation of the target area, and dose of radiotherapy. Further, we summarize large fraction radiotherapy (stereotactic body radiotherapy [SBRT]; proton therapy) in CCA and the development of immunotherapy and the use of targeted drugs combined with radiotherapy.
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Affiliation(s)
- Ningyu Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ai Huang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bohua Kuang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Xiao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yong Xiao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Hong Ma, ; Yong Xiao,
| | - Hong Ma
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Hong Ma, ; Yong Xiao,
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20
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Matsuyama R, Mori R, Ota Y, Homma Y, Yabusita Y, Hiratani S, Murakami T, Sawada Y, Miyake K, Shimizu Y, Kumamoto T, Endo I. Impact of Gemcitabine Plus S1 Neoadjuvant Chemotherapy on Borderline Resectable Perihilar Cholangiocarcinoma. Ann Surg Oncol 2022; 29:2393-2405. [PMID: 34994885 DOI: 10.1245/s10434-021-11206-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/30/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Surgical resection is the only curative strategy for perihilar cholangiocarcinoma (PHC), but recurrence rates are high even after purported curative resection. This study aimed to evaluate the efficacy and safety of gemcitabine/S-1 (GS) combination chemotherapy in the neoadjuvant setting. METHODS In an open-label, single-arm, phase 2 study, neoadjuvant chemotherapy (NAC) with GS, repeated every 21 days, was administered for three cycles to patients with histologic or cytologically confirmed borderline resectable (BR) PHC who were eligible for inclusion in the study. In this study, BR PHC was defined as positive for lymph node metastasis and for cancerous vascular invasion or Bismuth type 4 on preoperative imaging. The primary end point consisted of the 3- and 5-year survival rates. The secondary end points were feasibility, resection rate, and pathologic effect. RESULTS The study enrolled 60 patients between January 2011 and December 2016. With respect to toxicity, the major adverse effect was neutropenia, which reached grade 3 or 4 in 53.3% of cases. The overall disease control rate was 91.3%. The median survival time for the entire cohort was 30.3 months. For all the patients, the estimated 3-year survival rate was 44.1%, and the 5-year survival rate was 30.0%. Resection with curative intent was performed for 43 (71%) of the 60 patients. For 81% of the resected patients, R0 resection was performed, and Clavien-Dindo grade 3 complications or a higher morbidity rate was seen in 41% of the patients. The median survival time was 50.1 months for the resected and 14.8 months for the unresected patients. For the resected patients, the estimated 3-year survival rate was 55.8%, and the estimated 5-year survival rate was 36.4%. CONCLUSIONS Gemcitabine/S-1 combination NAC has promising efficacy and good tolerability for patients with BR PHC.
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Affiliation(s)
- Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
| | - Ryutaro Mori
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yohei Ota
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuki Homma
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yasuhiro Yabusita
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Seigo Hiratani
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takashi Murakami
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kentaro Miyake
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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21
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Oh MY, Kim H, Choi YJ, Byun Y, Han Y, Kang JS, Sohn H, Lee JM, Kwon W, Jang JY. Conversion surgery for initially unresectable extrahepatic biliary tract cancer. Ann Hepatobiliary Pancreat Surg 2021; 25:349-357. [PMID: 34402435 PMCID: PMC8382869 DOI: 10.14701/ahbps.2021.25.3.349] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/24/2021] [Accepted: 06/20/2021] [Indexed: 12/12/2022] Open
Abstract
Backgrounds/Aims Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents. Methods Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively. Results Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies. Conclusions Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.
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Affiliation(s)
- Moon Young Oh
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo Jin Choi
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yoonhyeong Byun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Heeju Sohn
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Min Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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22
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Zanetto A, Shalaby S, Gambato M, Germani G, Senzolo M, Bizzaro D, Russo FP, Burra P. New Indications for Liver Transplantation. J Clin Med 2021; 10:3867. [PMID: 34501314 PMCID: PMC8432035 DOI: 10.3390/jcm10173867] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases.
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Affiliation(s)
| | | | | | | | | | | | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (M.S.); (D.B.); (F.P.R.)
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23
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Choi SH, Rim CH, Shin IS, Yoon WS, Koom WS, Seong J. Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis. Liver Cancer 2021; 10:419-432. [PMID: 34721505 PMCID: PMC8527906 DOI: 10.1159/000518298] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/05/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS ART was shown to improve OS in all studies and in those selected for their reliable comparability.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea,*Chai Hong Rim,
| | - In-Soo Shin
- Graduate School of Education, AI Convergence Education, Dongguk University, Seoul, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
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24
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Lauterio A, De Carlis R, Centonze L, Buscemi V, Incarbone N, Vella I, De Carlis L. Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma. Cancers (Basel) 2021; 13:3657. [PMID: 34359560 PMCID: PMC8345178 DOI: 10.3390/cancers13153657] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/06/2021] [Accepted: 07/19/2021] [Indexed: 01/17/2023] Open
Abstract
Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.
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Affiliation(s)
- Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
| | - Vincenzo Buscemi
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
| | - Niccolò Incarbone
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
- School of Medicine and Surgery, University of Milano-Bicocca, 20162 Milan, Italy
| | - Ivan Vella
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
- Department of Surgical Sciences, University of Pavia, 27100 Pavia, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.L.); (R.D.C.); (V.B.); (N.I.); (I.V.); (L.D.C.)
- School of Medicine and Surgery, University of Milano-Bicocca, 20162 Milan, Italy
- International Center for Digestive Health, University of Milano-Bicocca, 20162 Milan, Italy
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25
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Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019. ACTA ACUST UNITED AC 2021; 28:1988-2006. [PMID: 34073199 PMCID: PMC8161825 DOI: 10.3390/curroncol28030185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/14/2021] [Accepted: 05/14/2021] [Indexed: 01/06/2023]
Abstract
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.
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26
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Nara S, Esaki M, Ban D, Takamoto T, Mizui T, Shimada K. Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer. Expert Rev Gastroenterol Hepatol 2021; 15:537-545. [PMID: 33793366 DOI: 10.1080/17474124.2021.1911645] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 03/30/2021] [Indexed: 12/13/2022]
Abstract
Introduction: Although the safety of biliary tract cancer resection has improved over the years, the recurrence rate is still high, and the postoperative prognosis remains low after biliary tract cancer resection. Therefore, the development of effective adjuvant therapy is essential to improve treatment outcomes. Because biliary tract cancer is rare compared with other gastrointestinal cancers, there have been only a small number of clinical trials of adjuvant therapy. However, in recent years, the results of several large-scale randomized controlled trials have been published, and clinical trials investigating the efficacy of new regimens are currently ongoing.Areas covered: This review presents the results of previously published important phase II and III clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and discusses their interpretation. The future direction of new research on resectable biliary tract cancer treatment is also discussed.Expert opinion: The foundations of large-scale clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer are underway, and new trials will establish evidence of their effectiveness. Additionally, breakthroughs in treatment through genetic and molecular research are expected.
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Affiliation(s)
- Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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27
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Rizzo A, Brandi G. Neoadjuvant therapy for cholangiocarcinoma: A comprehensive literature review. Cancer Treat Res Commun 2021; 27:100354. [PMID: 33756174 DOI: 10.1016/j.ctarc.2021.100354] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 03/11/2021] [Accepted: 03/13/2021] [Indexed: 02/07/2023]
Abstract
Biliary tract cancers (BTCs) comprise a heterogenous group of aggressive and rare malignancies arising in the bile duct outside or within the liver. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC) and ampulla of Vater cancer (AVC); according to the "historical" anatomical classification, CCAs are further subdivided into extrahepatic cholangiocarcinomas (eCCAs) - including distal (dCCA) and perihilar (pCCA) - and intrahepatic cholangiocarcinomas (iCCA). Notably enough, these subtypes reflect distinct features in terms of biology, epidemiology, prognosis and therapeutic strategies. Although surgical resection remains the only potentially curative treatment option for CCA patients, radical surgery is possible for only a small proportion of cases. Moreover, it has been observed that up to 50% of patients deemed resectable at diagnosis are found to be unresectable during exploratory laparotomy. Additionally, even following radical surgery, recurrence rates are high. Neoadjuvant therapy represents an appealing approach in this setting, where this therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant therapy in CCA and several questions remains unanswered, including the activity of systemic therapy in early stages of the disease, the optimal start time of treatment, patient selection and the length of neoadjuvant therapy. In this review, we will discuss available data on neoadjuvant systemic therapy in CCA, highlighting future directions in this setting, with a particular focus on recently published data and ongoing and recruiting trials.
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Affiliation(s)
- Alessandro Rizzo
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy.
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy; Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 15 Bologna, Italy
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28
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Fong ZV, Brownlee SA, Qadan M, Tanabe KK. The Clinical Management of Cholangiocarcinoma in the United States and Europe: A Comprehensive and Evidence-Based Comparison of Guidelines. Ann Surg Oncol 2021; 28:2660-2674. [PMID: 33646431 DOI: 10.1245/s10434-021-09671-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 01/18/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. METHODS We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. RESULTS There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. CONCLUSIONS Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.
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Affiliation(s)
- Zhi Ven Fong
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Sarah A Brownlee
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Motaz Qadan
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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29
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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30
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Moreau J, Lapeyre M, Benoit C, Pezet D, Biau J. [Intra and extra hepatic cholangiocarcinomas radiation therapy]. Cancer Radiother 2021; 25:175-181. [PMID: 33423966 DOI: 10.1016/j.canrad.2020.06.039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/09/2020] [Accepted: 06/13/2020] [Indexed: 01/06/2023]
Abstract
Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.
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Affiliation(s)
- J Moreau
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont Ferrand cedex 1, France.
| | - M Lapeyre
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont Ferrand cedex 1, France
| | - C Benoit
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont Ferrand cedex 1, France
| | - D Pezet
- Département de chirurgie digestive et hépatobiliaire, centre hospitalier universitaire hôpital Estaing, 63003 Clermont Ferrand cedex 1, France
| | - J Biau
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont Ferrand cedex 1, France
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31
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Gkika E, Hawkins MA, Grosu AL, Brunner TB. The Evolving Role of Radiation Therapy in the Treatment of Biliary Tract Cancer. Front Oncol 2021; 10:604387. [PMID: 33381458 PMCID: PMC7768034 DOI: 10.3389/fonc.2020.604387] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 11/04/2020] [Indexed: 12/13/2022] Open
Abstract
Biliary tract cancers (BTC) are a disease entity comprising diverse epithelial tumors, which are categorized according to their anatomical location as intrahepatic (iCCA), perihilar (pCCA), distal (dCCA) cholangiocarcinomas, and gallbladder carcinomas (GBC), with distinct epidemiology, biology, and prognosis. Complete surgical resection is the mainstay in operable BTC as it is the only potentially curative treatment option. Nevertheless, even after curative (R0) resection, the 5-year survival rate ranges between 20 and 40% and the disease free survival rates (DFS) is approximately 48–65% after one year and 23–35% after three years without adjuvant treatment. Improvements in adjuvant chemotherapy have improved the DFS, but the role of adjuvant radiotherapy is unclear. On the other hand, more than 50% of the patients present with unresectable disease at the time of diagnosis, which limits the prognosis to a few months without treatment. Herein, we review the role of radiotherapy in the treatment of cholangiocarcinoma in the curative and palliative setting.
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Affiliation(s)
- Eleni Gkika
- Department of Radiation Oncology, University Medical Centre Freiburg, Freiburg, Germany
| | - Maria A Hawkins
- Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, University Medical Centre Freiburg, Freiburg, Germany
| | - Thomas B Brunner
- Department of Radiation Oncology, University of Magdeburg, Magdeburg, Germany
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32
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Bennett S, Søreide K, Gholami S, Pessaux P, Teh C, Segelov E, Kennecke H, Prenen H, Myrehaug S, Callegaro D, Hallet J. Strategies for the delay of surgery in the management of resectable hepatobiliary malignancies during the COVID-19 pandemic. Curr Oncol 2020; 27:e501-e511. [PMID: 33173390 PMCID: PMC7606047 DOI: 10.3747/co.27.6785] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Objective We aimed to review data about delaying strategies for the management of hepatobiliary cancers requiring surgery during the covid-19 pandemic. Background Given the covid-19 pandemic, many jurisdictions, to spare resources, have limited access to operating rooms for elective surgical activity, including cancer, thus forcing deferral or cancellation of cancer surgeries. Surgery for hepatobiliary cancer is high-risk and particularly resource-intensive. Surgeons must critically appraise which patients will benefit most from surgery and which ones have other therapeutic options to delay surgery. Little guidance is currently available about potential delaying strategies for hepatobiliary cancers when surgery is not possible. Methods An international multidisciplinary panel reviewed the available literature to summarize data relating to standard-of-care surgical management and possible mitigating strategies to be used as a bridge to surgery for colorectal liver metastases, hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma. Results Outcomes of surgery during the covid-19 pandemic are reviewed. Resource requirements are summarized, including logistics and adverse effects profiles for hepatectomy and delaying strategies using systemic, percutaneous and radiation ablative, and liver embolic therapies. For each cancer type, the long-term oncologic outcomes of hepatectomy and the clinical tools that can be used to prognosticate for individual patients are detailed. Conclusions There are a variety of delaying strategies to consider if availability of operating rooms decreases. This review summarizes available data to provide guidance about possible delaying strategies depending on patient, resource, institution, and systems factors. Multidisciplinary team discussions should be leveraged to consider patient- and tumour-specific information for each individual case.
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Affiliation(s)
- S Bennett
- Canada: Department of Surgery, University of Toronto, Toronto, ON (Bennett, Callegaro, Hallet); Department of Radiation Oncology, University of Toronto, Toronto, ON (Myrehaug); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON (Hallet)
| | - K Søreide
- Norway: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, and Department of Clinical Medicine, University of Bergen, Bergen
| | - S Gholami
- United States: Division of Surgical Oncology, Department of Surgery, University of California, Davis, CA (Gholami); Virginia Mason Cancer Institute, Seattle, WA (Kennecke)
| | - P Pessaux
- France: Department of Surgery, Institut Hospitalo-Universitaire de Strasbourg, Strasbourg
| | - C Teh
- Philippines: Institute of Surgery, St. Luke's Medical Center, Quezon City; Department of Surgery, Makati Medical Center, Makati; and Department of General Surgery, National Kidney and Transplant Institute, Quezon City
| | - E Segelov
- Australia: Monash University and Monash Health, Melbourne
| | - H Kennecke
- United States: Division of Surgical Oncology, Department of Surgery, University of California, Davis, CA (Gholami); Virginia Mason Cancer Institute, Seattle, WA (Kennecke)
| | - H Prenen
- Belgium: Department of Oncology, University Hospital Antwerp, Antwerp
| | - S Myrehaug
- Canada: Department of Surgery, University of Toronto, Toronto, ON (Bennett, Callegaro, Hallet); Department of Radiation Oncology, University of Toronto, Toronto, ON (Myrehaug); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON (Hallet)
| | - D Callegaro
- Canada: Department of Surgery, University of Toronto, Toronto, ON (Bennett, Callegaro, Hallet); Department of Radiation Oncology, University of Toronto, Toronto, ON (Myrehaug); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON (Hallet)
- Italy: Department of Surgery, Fondazione irccs Istituto Nazionale Tumori, Milan
| | - J Hallet
- Canada: Department of Surgery, University of Toronto, Toronto, ON (Bennett, Callegaro, Hallet); Department of Radiation Oncology, University of Toronto, Toronto, ON (Myrehaug); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON (Hallet)
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Le VH, O'Connor VV, Li D, Melstrom LG, Fong Y, DiFronzo AL. Outcomes of neoadjuvant therapy for cholangiocarcinoma: A review of existing evidence assessing treatment response and R0 resection rate. J Surg Oncol 2020; 123:164-171. [PMID: 32974932 DOI: 10.1002/jso.26230] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/03/2020] [Accepted: 09/05/2020] [Indexed: 12/15/2022]
Abstract
Adjuvant chemotherapy for cholangiocarcinoma (CCA) has not been shown to gain significant improvements in survival. Factors contributing to suboptimal treatment response include aggressive disease biology and late clinical presentation. When feasible, surgical resection is the first line of treatment. Yet, recurrence remains high and long-term survival is rare. Neoadjuvant therapy is an appealing approach, with oncologic advantages in allowing the treatment of occult systemic disease and selection of patients most likely to benefit from radical surgery. However, given the surgery-first treatment paradigm for CCA, there is a paucity of data supporting neoadjuvant therapy. This review summarizes the current evidence on treatment response and margin-negative (R0) resection rate associated with neoadjuvant therapy for CCA.
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Affiliation(s)
- Viet H Le
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Victoria V O'Connor
- Department of Surgery, Kaiser Permanente - Los Angeles Medical Center, Los Angeles, California, USA
| | - Daneng Li
- Department of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, California, USA
| | - Laleh G Melstrom
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Andrew L DiFronzo
- Department of Surgery, Kaiser Permanente - Los Angeles Medical Center, Los Angeles, California, USA
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Ku D, Tang R, Pang T, Pleass H, Richardson A, Yuen L, Lam V. Survival outcomes of hepatic resections in Bismuth-Corlette type IV cholangiocarcinoma. ANZ J Surg 2020; 90:1604-1614. [PMID: 31840387 DOI: 10.1111/ans.15531] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/22/2019] [Accepted: 09/26/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Surgical resection for Bismuth-Corlette type IV (BC-IV) hilar cholangiocarcinomas, also termed Klatskin tumours are technically challenging and were once considered unresectable tumours. Following advances in hepatobiliary imaging and surgical techniques, emerging evidence suggests that surgical resection is a viable avenue for long-term survival. We aimed to identify factors affecting survival outcomes of hepatic resections for BC-IV cholangiocarcinomas. METHOD A systematic review was performed across multiple databases and several clinical trial registries. Two reviewers independently screened and selected papers that contained survival data on BC-IV cholangiocarcinoma after hepatic resections. RESULTS Of 13 499 papers from our search result, 21 papers satisfied the inclusion criteria. The median post-operative survival was 30.8 months. The average 1- and 5-year post-operative survivals were 61.6 and 33.3%, respectively. Predictors of long-term survival included achievement of R0 margins, minimisation of operative time and reduction intra-operative blood loss. CONCLUSION Our analysis demonstrates improving post-operative outcomes and survival in surgical resection of BC-IV cholangiocarcinoma and suggests that radical surgical resection is a valid treatment option for the disease.
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Affiliation(s)
- Dominic Ku
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Reuben Tang
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
| | - Tony Pang
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Henry Pleass
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Arthur Richardson
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Lawrence Yuen
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Vincent Lam
- General Surgical Department, Westmead Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
- Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
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Kaiser GM, Paul A, Sgourakis G, Molmenti EP, DechÊNe A, Trarbach T, Stuschke M, Baba HA, Gerken G, Sotiropoulos GC. Novel Prognostic Scoring System after Surgery for Klatskin Tumor. Am Surg 2020. [DOI: 10.1177/000313481307900136] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Klatskin tumor is a rare hepatobiliary malignancy whose outcome and prognostic factors are not clearly documented. Between April 1998 and January 2007, 96 patients with hilar cholangiocarcinoma underwent resection. Data were collected prospectively. Thirty-one variables were evaluated for prognostic significance. There were 40 trisectionectomies, 40 hemihepatectomies, five central hepatectomies, and 11 biliary hilar resections. Thirty-seven (n = 37) patients required vascular reconstruction. There were 68 R0, 26 R1, and two R2 resections. Age ( P = 0.048), pT status ( P = 0.046), R class ( P = 0.034), and adjuvant chemoradiation ( P = 0.045) showed predictive significance by multivariate Cox proportional hazard regression analysis. A point scoring system was determined as follows: age younger than 62 years:age 62 years or older = 1:2 points; pT1:pT2 to 4 = 1:2 points; R0:R1/2 = 1:2 points; and chemoradiation yes:no = 1:2 points. The only model that reached statistical significance ( P = 0.0332) described the following three groups: score 6 or less; score = 7; and score = 8. Median survival for score 6 or less, score = 7, and score = 8 was 26.5, 12, and 2.2 months, respectively ( P = 0.032). The corresponding 1- and 3-year survival rates were 73 to 56 per cent, 52 to 38 per cent, and 17 to 0 per cent, respectively. We propose a scoring system predictive of long-term surgical outcome that could potentially improve patient selection for further postoperative oncologic treatment for Klatskin tumors.
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Affiliation(s)
- Gernot M. Kaiser
- Department of General, Visceral and Transplantation Surgery, the
| | - Andreas Paul
- Department of General, Visceral and Transplantation Surgery, the
| | - George Sgourakis
- Department of General, Visceral and Transplantation Surgery, the
| | | | | | | | | | - Hideo A. Baba
- Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, the
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Abstract
Distal cholangiocarcinoma is a rare malignancy with a dismal prognosis. Because of its location and aggressive nature, patients often present with locally advanced or metastatic disease, and effective treatment options are limited. For patients with resectable disease, surgery is the only chance for cure, but achieving an R0 resection is paramount. Optimal adjuvant therapy in resectable disease remains under investigation. Randomized controlled trials investigating neoadjuvant therapy and its impact on resectability and long-term outcomes are needed to continue to improve the outcomes of patients with distal cholangiocarcinoma.
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Affiliation(s)
- Rachel M Lee
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, 4th Floor, Atlanta, GA 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Emory Liver and Pancreas Center, Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, 4th Floor, Atlanta, GA 30322, USA.
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Sapisochin G, Ivanics T, Subramanian V, Doyle M, Heimbach JK, Hong JC. Multidisciplinary treatment for hilar and intrahepatic cholangiocarcinoma: A review of the general principles. Int J Surg 2020; 82S:77-81. [PMID: 32380231 DOI: 10.1016/j.ijsu.2020.04.067] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/25/2020] [Accepted: 04/28/2020] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.
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Affiliation(s)
- Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
| | - Tommy Ivanics
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
| | - Vijay Subramanian
- Transplant, Hepatobiliary and Pancreatic Surgery, Tampa General Hospital, Tampa, FL, USA
| | - Majella Doyle
- Division of Transplant and Hepatobiliary and Pancreatic Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | - Julie K Heimbach
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Johnny C Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
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Miyahara Y, Takashi S, Shimizu Y, Ohtsuka M. The prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with distal bile duct cancer. World J Surg Oncol 2020; 18:78. [PMID: 32321522 PMCID: PMC7178599 DOI: 10.1186/s12957-020-01847-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
Background A growing body of evidence suggests that inflammatory response markers such as the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are associated with outcomes of various malignancies. However, no study has reported the prognostic value of NLR and LMR in patients with distal bile duct cancer (DBDC) to date. We investigated the prognostic significance of these inflammatory markers in patients with DBDC who underwent radical resection. Methods The study included 40 patients diagnosed with DBDC who underwent pancreaticoduodenectomy at Narita Red Cross Hospital between January 2000 and December 2017. The cutoff values for these markers were determined by receiver operating characteristic curve analysis. Survival curves are estimated for each group in the study considered separately using the Kaplan-Meier method. The association between overall survival (OS) and the NLR, LMR, and other prognostic factors was investigated using log-rank test and multivariate Cox proportional hazards regression analysis. Results Corresponding to the point with the maximum combined sensitivity and specificity on the ROC curve, the best cutoff value for NLR and LMR was determined to be 3.14 and 4.55, respectively. Most clinicopathological factors were not associated with the NLR and LMR based on these cutoff values. However, serum albumin levels were associated with both the NLR and LMR (P = 0.011 and P = 0.023, respectively), and serum carbohydrate antigen 19-9 (CA 19-9) levels were also associated with the LMR (P = 0.030). Univariate analysis showed that a high NLR (P < 0.001), low LMR (P = 0.002), hypoalbuminemia (P = 0.004), high serum CA 19-9 levels (P = 0.008), and lymph node metastasis (P = 0.033) were significantly associated with poor survival rates. Multivariate analysis showed that a high NLR (hazard ratio 5.799, 95% confidence interval 1.188–28.32, P = 0.030) and a low LMR (hazard ratio 4.837, 95% confidence interval 1.826–2.331, P = 0.025) were independent prognostic factors for OS. Conclusion Both NLR and LMR may serve as significant independent preoperative prognostic indicators of disease in patients with DBDC who undergo radical resection.
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Affiliation(s)
- Yoji Miyahara
- Department of Surgery, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita-shi, Chiba Prefecture, 286-0041, Japan. .,Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba Prefecture, 260-8677, Japan.
| | - Shida Takashi
- Shida Clinic, 1970-1-2 Ne, Shiroi-shi, Chiba Prefecture, 270-1431, Japan
| | - Yoshiaki Shimizu
- Department of Surgery, Japanese Red Cross Narita Hospital, 90-1 Iida-cho, Narita-shi, Chiba Prefecture, 286-0041, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba Prefecture, 260-8677, Japan
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Baltatzis M, Jegatheeswaran S, Siriwardena AK. Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review. Hepatobiliary Pancreat Dis Int 2020; 19:103-108. [PMID: 32147487 DOI: 10.1016/j.hbpd.2020.02.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 02/17/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase II studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA. DATA SOURCES A systematic review of the literature for reports of patients undergoing resection of PH-CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings "hilar cholangiocarcinoma", "Klatskin", "chemoradiotherapy" and "chemotherapy" were used. Data were extracted on demographic profile, disease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. RESULTS There were seven reports on this topic, with median recruitment period of 14 (range 4-31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9-28) months and 5-year survival 20%. CONCLUSIONS There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.
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Affiliation(s)
- Minas Baltatzis
- Regional Hepato-Pancreato-Biliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK
| | - Santhalingam Jegatheeswaran
- Regional Hepato-Pancreato-Biliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK
| | - Ajith K Siriwardena
- Regional Hepato-Pancreato-Biliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK; Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9WL, UK.
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40
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Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Turgeon MK, Maithel SK. Cholangiocarcinoma: a site-specific update on the current state of surgical management and multi-modality therapy. Chin Clin Oncol 2019; 9:4. [PMID: 31500433 DOI: 10.21037/cco.2019.08.09] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 08/07/2019] [Indexed: 12/14/2022]
Abstract
Biliary tract cancers (BTC) are rare, heterogeneous malignancies that include cholangiocarcinoma and gallbladder cancer (GBC). Cholangiocarcinoma subtypes differ by anatomic location and molecular profile. Currently, resection with lymphadenectomy is the only curative treatment of locally advanced cholangiocarcinoma. Given the high risk of recurrence, multi-modality therapy spanning surgery, chemotherapy, and radiation therapy should be considered. Current data is discordant and there is limited prospective data to support an optimal treatment regimen, though recent studies have demonstrated the utility of adjuvant chemotherapy and chemoradiation in specific settings and patient populations. There is a potential role for neoadjuvant chemotherapy in patients with resectable disease or chemoradiation in select patients with unresectable, locally advanced disease. Randomized clinical trials are necessary to establish the effectiveness of therapies specific to disease sites, especially with the emerging role of immunotherapy and targeted therapy to actionable mutations.
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Affiliation(s)
- Michael K Turgeon
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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Moris D, Kostakis ID, Machairas N, Prodromidou A, Tsilimigras DI, Ravindra KV, Sudan DL, Knechtle SJ, Barbas AS. Comparison between liver transplantation and resection for hilar cholangiocarcinoma: A systematic review and meta-analysis. PLoS One 2019; 14:e0220527. [PMID: 31365594 PMCID: PMC6668826 DOI: 10.1371/journal.pone.0220527] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 07/17/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hilar cholangiocarcinoma (hCCA) is a rare and aggressive malignancy with R0 resection being currently the only option for long-term survival. With the improvement in the outcomes of liver transplantation (LT), the indications for LT have expanded to include other malignant tumors, such as hCCA. The aim of the present analysis is to demonstrate and critically evaluate the outcomes of LT compared to resection with curative intent in patients with hCCA. METHODS We systematically searched the literature for articles published up to May 2018. The following algorithm was applied ((hilar cholangiocarcinoma) OR (perihilar cholangiocarcinoma) OR klatskin$ OR (bile duct neoplasm) OR cholangiocarcinoma) AND (transplant$ OR graft$). RESULTS Neoadjuvant treatment with chemotherapy and radiation therapy was far more common in the LT group, with very few patients having received preoperative therapy in the resection group (p = 0.0005). Moreover, length of hospital stay was shorter after LT than after resection (p<0.00001). In contrast, no difference was found between the two treatment methods concerning postoperative mortality (p = 0.57). There was a trend towards longer overall survival after LT in comparison with resection. This was not obvious in the first year postoperatively, however, the advantage of LT over resection became obvious at 3 years after the operation (p = 0.02). CONCLUSIONS In non-disseminated unresectable tumors, LT seems to have a non-inferior survival. In the same patients, neoadjuvant chemoradiotherapy and/or strict selection criteria may contribute to superior survival outcomes compared to curative-intent resection. Due to the scarcity of level 1 evidence, it remains unclear whether LT should be increasingly considered for technically resectable early stage hCCA.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Ioannis D. Kostakis
- Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Nikolaos Machairas
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Prodromidou
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Diamantis I. Tsilimigras
- Third Department of Surgery, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kadiyala V. Ravindra
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Debra L. Sudan
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Stuart J. Knechtle
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
| | - Andrew S. Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC, United States of America
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Cloyd JM, Prakash L, Vauthey JN, Aloia TA, Chun YS, Tzeng CW, Kim MP, Lee JE, Katz MHG. The role of preoperative therapy prior to pancreatoduodenectomy for distal cholangiocarcinoma. Am J Surg 2019; 218:145-150. [PMID: 30224070 DOI: 10.1016/j.amjsurg.2018.08.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 07/31/2018] [Accepted: 08/31/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Although increasingly administered to patients with pancreatic ductal adenocarcinoma, the role of preoperative therapy for patients with distal cholangiocarcinoma is undefined. METHODS All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between 1999 and 2014 were retrospectively reviewed. Differences in clinicopathologic characteristics and overall survival (OS) were compared between patients who underwent surgery de novo and those who received preoperative therapy. RESULTS Twenty-one patients (46.7%) received preoperative therapy and 24 (53.3%) did not. Five-year OS rates were not statistically significantly different between patients who received preoperative therapy and those who did not (46.6% vs 49.1%, p > 0.05). On multivariate cox proportional hazards analysis, lymph node positivity was the strongest predictor of OS (HR 4.68 (95%CI 1.52-14.42)). Whereas preoperative therapy was not associated with improved OS (HR 1.06 (95%CI 0.42-2.66)), the receipt of either pre- or post-operative therapy was (HR 0.40 (95%CI 0.16-1.00)). CONCLUSION While these results do not support the routine administration of preoperative therapy to patients with distal cholangiocarcinoma, it may be an alternative treatment strategy appropriate for a subset of patients with high risk clinical or pathologic features.
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Affiliation(s)
- Jordan M Cloyd
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
| | - Laura Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Michel P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA
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Frosio F, Mocchegiani F, Conte G, Bona ED, Vecchi A, Nicolini D, Vivarelli M. Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma: Review of the literature. World J Gastrointest Surg 2019; 11:279-286. [PMID: 31367275 PMCID: PMC6658363 DOI: 10.4240/wjgs.v11.i6.279] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 05/29/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA (iCCA), hilar CCA (hCCA) and distal CCA (dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy (RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant (OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.
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Affiliation(s)
- Fabio Frosio
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Federico Mocchegiani
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Grazia Conte
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Enrico Dalla Bona
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Andrea Vecchi
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Daniele Nicolini
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
| | - Marco Vivarelli
- Unit of Hepato-pancreato-biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60126, Italy
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Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol 2019; 45:1432-1438. [PMID: 30914290 DOI: 10.1016/j.ejso.2019.03.023] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/01/2019] [Accepted: 03/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear. PATIENTS AND METHODS Using the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model. RESULTS Of the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64-0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group. CONCLUSION In this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.
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Affiliation(s)
| | - Hao Xie
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Irbaz Bin-Riaz
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Prabin Sharma
- Department of Gastroenterology, Yale New Haven Health - Bridgeport Hospital, Bridgeport, CT, 06610, USA
| | - Urshila Durani
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Gaurav Goyal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Bijan Borah
- Robert D. and Patricia E. Kern Mayo Clinic Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Mitesh J Borad
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA
| | | | - Amit Mahipal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
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Endo I. Congress presidential address to the 30th meeting of the JSHBPS: the second opening of Japan on the way to a bright future. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:1-8. [PMID: 30575328 DOI: 10.1002/jhbp.595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
The 30th meeting of the JSHBPS is the first domestic meeting of our society to have been organized completely in English. In that sense, we have established the theme of the 30th meeting of the JSHBPS as "The Second Opening of Japan on the Way to a Bright Future". Last 30 years, several strategies have been undertaken to battle hepatobiliary (HPB) malignancies, such as aggressive operative procedures, operative planning using state-of-the-art technologies, neoadjuvant therapy, conversion surgery for initially unresectable diseases, and immunomodulation. According to the rapid development of precision medicine, HBP surgeons should have a literacy for individualized therapy. Here, I review recent improvements in regard to HBP surgery. In addition, education for the next generations should be our highest priority. Collaboration with foreign researchers is the most effective tool to promote personal growth.
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Affiliation(s)
- Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
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Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, Matsumoto M, Hata Y, Noda Y, Sui K, Sueda T. Chemoradiotherapy for Initially Unresectable Locally Advanced Cholangiocarcinoma. World J Surg 2018; 42:2910-2918. [PMID: 29511872 DOI: 10.1007/s00268-018-4558-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. METHODS Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50 Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. RESULTS Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37 months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10 months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). CONCLUSIONS Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan.
| | - Yasuo Shima
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Takehiro Okabayashi
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Yuji Negoro
- Department of Medical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Yasuhiro Shimada
- Department of Medical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Jun Iwata
- Departments of Diagnostic Pathology, Kochi Health Sciences Center, Kochi, Japan
| | - Manabu Matsumoto
- Departments of Diagnostic Pathology, Kochi Health Sciences Center, Kochi, Japan
| | - Yasuhiro Hata
- Departments of Radiology, Kochi Health Sciences Center, Kochi, Japan
| | - Yoshihiro Noda
- Departments of Radiology, Kochi Health Sciences Center, Kochi, Japan
| | - Kenta Sui
- Departments of Gastroenterological Surgery, Kochi Health Sciences Center, 2125 Ike, Kochi, Japan
| | - Taijiro Sueda
- Department of Surgery, Applied Life Sciences Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Wiggers JK, Groot Koerkamp B, van Klaveren D, Coelen RJ, Nio CY, Allen PJ, Besselink MG, Busch OR, D'Angelica MI, DeMatteo RP, Kingham TP, van Gulik TM, Jarnagin WR. Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging. J Am Coll Surg 2018; 227:238-246.e2. [PMID: 29627334 PMCID: PMC6089225 DOI: 10.1016/j.jamcollsurg.2018.03.041] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 03/20/2018] [Accepted: 03/21/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Many patients with resectable perihilar cholangiocarcinoma (PHC) on imaging are diagnosed intraoperatively with occult metastatic or locally advanced disease, precluding a curative-intent resection. This study aimed to develop and validate a preoperative risk score. STUDY DESIGN Patients with resectable PHC on imaging who underwent operations in 2 high-volume centers (US and Europe) between 2000 and 2015 were included. Multivariable logistic regression analysis was used to develop the risk score. Cross-validation was used to validate the score, alternating the 2 centers as "training" and "testing" datasets. RESULTS Of 566 patients who underwent operations, 309 (55%) patients had a resection, and in 257 (45%) patients, a curative-intent resection was precluded due to distant metastasis (n = 151 [27%]) or locally advanced disease (n = 106 [19%]). Preoperative predictors included bilirubin >2 mg/dL, bile duct involvement on imaging, portal vein involvement on imaging (≥180 degrees), hepatic artery involvement on imaging (≥180 degrees), and suspicious lymph nodes on imaging. The new risk score (c-index 0.75 after cross-validation) provided significantly more accurate predictions than the Bismuth classification (c-index 0.62), Blumgart T-staging (c-index 0.67), and cTNM staging (c-index 0.68). The new risk score identified 4 risk groups for occult metastatic or locally advanced disease: low (14.7%), intermediate (29.5%), high (47.3%), and very high risk (81.3%). The preoperative score groups also predicted survival after operation, irrespective of intraoperative findings (p < 0.001). CONCLUSIONS The validated risk score can predict occult distant metastatic or locally advanced PHC based on 5 preoperatively available factors. The score can be useful in preoperative shared decision making and selection of patients in neoadjuvant clinical trials.
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Affiliation(s)
- Jimme K Wiggers
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David van Klaveren
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Robert J Coelen
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - C Yung Nio
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | | | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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Lidsky ME, Jarnagin WR. Surgical management of hilar cholangiocarcinoma at Memorial Sloan Kettering Cancer Center. Ann Gastroenterol Surg 2018; 2:304-312. [PMID: 30003193 PMCID: PMC6036362 DOI: 10.1002/ags3.12181] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 05/20/2018] [Indexed: 02/06/2023] Open
Abstract
Hilar cholangiocarcinoma, which represents approximately 60% of biliary tract malignancies, is increasing in incidence and presents an ongoing challenge for patients and hepatobiliary surgeons. Although the majority of patients present with advanced disease, the remaining minority of patients are best treated with surgical resection or transplant. Transplant is typically reserved for locally unresectable tumors often in the setting of underlying hepatic dysfunction and will not be discussed herein. This review, therefore, focuses on oncological resection and the strategies implemented for the treatment of hilar cholangiocarcinoma at a quaternary referral center, including preoperative considerations such as patient selection and optimization of the future liver remnant, nuances to the operative approach for these tumors such as resection under low central venous pressure and management of the bile duct, as well as postoperative management.
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Affiliation(s)
- Michael E. Lidsky
- Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkNYUSA
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Abstract
Liver transplant (LT) for perihilar cholangiocarcinoma (CCA) offers an opportunity for survival among patients with early-stage but anatomically unresectable disease. The 5-year survival rate after LT is 65% to 70%, higher among patients with primary sclerosing cholangitis, who are often diagnosed earlier, and lower among patients with de novo CCA. The results of LT for hilar CCA, along with recent limited data suggesting favorable survival among patients with very early intrahepatic CCA (ICC), have reignited interest in the subject. This article discusses LT following neoadjuvant therapy for CCA and the early data on LT alone for ICC.
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Affiliation(s)
- Daniel Zamora-Valdes
- Division of Transplantation Surgery, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA
| | - Julie K Heimbach
- Division of Transplantation Surgery, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA.
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