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Kawashima J, Akabane M, Khalil M, Woldesenbet S, Endo Y, Sahara K, Cauchy F, Aucejo F, Marques HP, Lopes R, Rodriguea A, Hugh T, Shen F, Maithel SK, Groot Koerkamp B, Popescu I, Kitago M, Weiss MJ, Martel G, Pulitano C, Aldrighetti L, Poultsides G, Ruzzenente A, Bauer TW, Gleisner A, Endo I, Pawlik TM. Tumour burden predicts outcomes after curative resection of multifocal intrahepatic cholangiocarcinoma. Br J Surg 2025; 112:znaf050. [PMID: 40156894 DOI: 10.1093/bjs/znaf050] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/17/2025] [Accepted: 02/11/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Liver resection for multifocal intrahepatic cholangiocarcinoma (ICC) remains controversial due to a poor prognosis, driven by aggressive tumour biology. The aim of this study was to stratify multifocal ICC patients to identify those who are likely to benefit from resection. METHODS Patients who underwent upfront curative-intent hepatectomy for ICC were identified from an international multi-institutional database. Among patients with multifocal tumours, overall survival (OS) was analysed using multivariable Cox regression to identify prognostic factors. Tumour burden score (TBS) was used for stratification of multifocal ICC, with the optimal cut-off determined via restricted cubic spline (RCS) analysis. RESULTS Of 1502 patients, 208 (13.8%) had multifocal ICC. Among them, independent predictors of prognosis included TBS (HR 1.09), ASA grade >II (HR 1.48), cirrhosis (HR 2.05), periductal infiltrating/mass forming plus periductal infiltrating morphological subtype (HR 1.58), and receipt of adjuvant chemotherapy (HR 0.59). RCS analysis identified a TBS of 7.0 as the optimal cut-off. Notably, multifocal ICC patients with a low TBS (<7.0) demonstrated comparable 3-year OS to solitary ICC patients with AJCC stage II/III. In contrast, patients with a high TBS (≥7.0) and multifocal ICC exhibited the worst prognosis (3-year OS: stage I and solitary 67.1%, stage II/III and solitary 43.2%, low TBS and multifocal 43.4%, and high TBS and multifocal 17.8% (P < 0.001)). CONCLUSION Whereas patients with high-TBS multifocal ICC had a poor prognosis, individuals with low-TBS multifocal ICC demonstrated survival outcomes comparable to solitary ICC patients. These findings emphasize the importance of stratifying patients by tumour burden to guide surgical decision-making and optimize treatment strategies for multifocal ICC.
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Affiliation(s)
- Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Mujtaba Khalil
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Yutaka Endo
- Department of Transplant Surgery, University of Rochester Medical Center, Rochester, New York, USA
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - François Cauchy
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - Federico Aucejo
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, Ohio, USA
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Rita Lopes
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Tom Hugh
- Department of Surgery, The University of Sydney, Sydney, New South Wales, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institution, Emory University, Atlanta, Georgia, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Matthew J Weiss
- Department of Surgery, Cancer Institute, Northwell Health, New Hyde Park, New York, USA
| | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | | | - George Poultsides
- Department of Surgery, Stanford University, Stanford, California, USA
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Ana Gleisner
- Department of Surgery, University of Colorado Denver, Denver, Colorado, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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Park W, Lee SK, Gwack J, Lee SY, Cho YG, Kang SB, Park J. Dysbiosis of Bile Microbiota in Cholangiocarcinoma Patients: A Comparison with Benign Biliary Diseases. Int J Mol Sci 2025; 26:1577. [PMID: 40004041 PMCID: PMC11855699 DOI: 10.3390/ijms26041577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary diseases as a control (CTR) group. Microbial profiling was conducted using next-generation sequencing (NGS), targeting the V3-V4 regions of the 16S rRNA gene, followed by bioinformatics analysis using the VSEARCH and EzBioCloud platforms. Alpha and beta diversity analyses were performed to assess microbial richness and structural differences. The linear discriminant analysis effect size (LEfSe) was utilized to identify potential microbial biomarkers. Results: This study identified distinct microbial profiles in the two groups at both the phylum and genus levels. In the CTR group, Pseudomonadota (65%) was the dominant phyla, while Bacillota (49%) was more abundant in the CCA group. At the genus level, Escherichia (29%), Enterobacteriaceae (12%), Enterococcus (8%), Ralstonia (8%), and Clostridium (5%) were more prevalent in the CTR group, whereas Streptococcus (34%), Ralstonia (8%), and Veillonella (5%) were dominant in the CCA group. Although an alpha diversity analysis showed no statistically significant differences in species richness or diversity between groups, a beta diversity analysis revealed significant structural differences associated with disease severity. Our comparative microbiome study using LEfSe analysis suggested a statistically significant inhibition of normal intestinal bacterial flora in patients with CCA who had not received any treatment. These findings suggest that microbial dysbiosis may play a role in the pathogenesis of CCA. Specific microbial taxa were identified as potential biomarkers for distinguishing benign from malignant diseases. These results underscore the potential role of microbial dysbiosis in CCA pathogenesis and highlight the bile microbiota's utility as a diagnostic marker for biliary diseases.
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Affiliation(s)
- Wonsuk Park
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Sang Kuon Lee
- Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Jin Gwack
- Department of Prevention Medicine, College of Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea;
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
| | - Seung Yeob Lee
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Yong Gon Cho
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
| | - Sang-Bum Kang
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
| | - Joonhong Park
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (S.Y.L.); (Y.G.C.)
- Department of Laboratory Medicine, Jeonbuk National University College of Medicine and Hospital, Jeonju 54907, Republic of Korea
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Cai Y, Wen W, Xia Y, Wan R. The Efficacy and Safety of Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Programmed Death (PD)-1 Inhibitors for Unresectable Intrahepatic Cholangiocarcinoma: A Retrospective Study. Curr Oncol 2025; 32:87. [PMID: 39996887 PMCID: PMC11854701 DOI: 10.3390/curroncol32020087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/19/2025] [Accepted: 01/23/2025] [Indexed: 02/26/2025] Open
Abstract
Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3-4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases.
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Affiliation(s)
| | | | | | - Renhua Wan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang 330006, China
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Maspero M, Sposito C, Bongini MA, Cascella T, Flores M, Maccauro M, Chiesa C, Niger M, Pietrantonio F, Leoncini G, Bellia V, Bhoori S, Mazzaferro V. Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study. Transpl Int 2024; 37:13641. [PMID: 39544321 PMCID: PMC11560448 DOI: 10.3389/ti.2024.13641] [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: 08/09/2024] [Accepted: 10/18/2024] [Indexed: 11/17/2024]
Abstract
Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.
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Affiliation(s)
- Marianna Maspero
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Marco A. Bongini
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Tommaso Cascella
- Interventional Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Marco Maccauro
- Nuclear Medicine and Physics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Chiesa
- Nuclear Medicine and Physics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Monica Niger
- Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | | | - Valentina Bellia
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sherrie Bhoori
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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5
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Dong X, Zhang P, Ye C, Li L. A personalized prognostic model for long-term survival in patients with intrahepatic cholangiocarcinoma: a retrospective cohort study. Ann Surg Treat Res 2024; 107:16-26. [PMID: 38978684 PMCID: PMC11227918 DOI: 10.4174/astr.2024.107.1.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 03/30/2024] [Accepted: 04/19/2024] [Indexed: 07/10/2024] Open
Abstract
Purpose This study aimed to determine the optimal cutoff points for age and tumor size of patients with intrahepatic cholangiocarcinoma (ICC) and to establish and verify a predictive nomogram of overall survival at 1, 3, and 5 years. Methods From the SEER (Surveillance, Epidemiology, and End Results) database, 1,325 ICC patients were selected and randomly divided into training and testing cohorts at a 7:3 ratio. Using the X-tile software, age and tumor size were classified into 3 subgroups: ≤61, 62-74, and ≥75 years and ≤35, 36-55, and ≥56 mm. Subsequently, univariate and multivariate Cox regression analyses were performed using the R software in the training cohort to determine independent risk factors, compile the prediction nomogram, and verify it with the testing cohort findings. Results The C-indexes of the new prediction nomograms in the training and testing cohorts were 0.738 (95% confidence interval [CI], 0.718-0.758) and 0.750 (95% CI, 0.72-0.78), respectively. Furthermore, the areas under the 1-, 3-, and 5-year receiver operating characteristic (ROC) curves based on the nomogram were 0.792, 0.853, and 0.838, respectively, higher than the ROC based on the 7th and 8th editions of the American Joint Cancer Commission (AJCC) staging system. Conclusion This study established and verified a prognostic nomogram that improved the accuracy of the 1-, 3-, and 5-year survival predictions for ICC patients, compared with that based on the 7th and 8th editions of the AJCC staging system, and can help clinicians make personalized survival predictions.
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Affiliation(s)
- Xianhui Dong
- Center for Pre-Disease Treatment and Health Management, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
| | - Pengwei Zhang
- Center for Pre-Disease Treatment and Health Management, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
| | | | - Li Li
- Hangzhou Normal University, Hangzhou, China
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Wang WQ, Li J, Lv X, Wang JL, Zhang EL, Zhang BH, Xiao ZY, Liang BY, Huang ZY. Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis. HPB (Oxford) 2024; 26:753-763. [PMID: 38485565 DOI: 10.1016/j.hpb.2024.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 12/27/2023] [Accepted: 01/26/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.
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Affiliation(s)
- Wen-Qiang Wang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.; Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xing Lv
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-Lin Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Hao Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhen-Yu Xiao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China..
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China..
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7
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Hissong E, Assaad MA, Bal M, Reed KA, Fornelli A, Levine MF, Gundem G, Semaan A, Orr CE, Sakhadeo U, Manohar J, Sigouros M, Wilkes D, Sboner A, Montgomery EA, Graham RP, Medina-Martínez JS, Robine N, Fang JM, Choi EYK, Westerhoff M, la Mora JDD, Caudell P, Yantiss RK, Papaemmanuil E, Elemento O, Sigel C, Jessurun J, Mosquera JM. NIPBL::NACC1 Fusion Hepatic Carcinoma. Am J Surg Pathol 2024; 48:183-193. [PMID: 38047392 PMCID: PMC11238093 DOI: 10.1097/pas.0000000000002159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.
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Affiliation(s)
- Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Majd Al Assaad
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
| | - Munita Bal
- Department of Pathology, Tata Memorial Centre, Mumbai, India
| | - Katelyn A. Reed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Adele Fornelli
- U.O. Anatomia Patologica, Ospedale Maggiore, Bologna, Italy
| | | | | | - Alissa Semaan
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
| | - Christine E. Orr
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Uma Sakhadeo
- Department of Pathology, Tata Memorial Centre, Mumbai, India
| | - Jyothi Manohar
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
| | - Michael Sigouros
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
| | - David Wilkes
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
| | - Andrea Sboner
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY
| | - Elizabeth A. Montgomery
- Department of Pathology and Laboratory Medicine, University of Miami Hospital (UMH), Miami, FL
| | - Rondell P. Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | | | | | - Jiayun M Fang
- Department of Pathology, University of Michigan, Ann Arbor, MI
| | | | | | - Jesus Delgado-de la Mora
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de México, CDMX, Mexico
| | | | - Rhonda K. Yantiss
- Department of Pathology and Laboratory Medicine, University of Miami Hospital (UMH), Miami, FL
| | | | - Olivier Elemento
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY
| | - Carlie Sigel
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - José Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Juan Miguel Mosquera
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
- Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian, New York, NY
- New York Genome Center, New York, NY
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8
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Lozada ME, Zhang N, Jin W, Wongjarupong N, Yang JD, Petersen MM, Prasai K, Amakye DO, Harmsen WS, Chaudhary S, Bathe O, Borad M, Patel TC, Gores GJ, Therneau TM, Roberts LR. CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation. Am J Gastroenterol 2023; 118:2173-2183. [PMID: 36940423 PMCID: PMC10739641 DOI: 10.14309/ajg.0000000000002258] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 02/06/2023] [Indexed: 03/22/2023]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.
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Affiliation(s)
- Maria E. Lozada
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Department of Surgery, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, United States
| | - Ning Zhang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Integrated TCM & Western Medicine Department, the Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Weidong Jin
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Department of General Surgery, Wuhan General Hospital of Guangzhou Military, Wuhan, China
| | - Nicha Wongjarupong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN
| | - Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Division of Digestive and Liver Diseases, Department of Internal Medicine, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Molly M. Petersen
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Kritika Prasai
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
| | - Dominic O. Amakye
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, Athens, GA
| | - William S. Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN
| | | | - Oliver Bathe
- Department of Surgery, University of Calgary, Alberta, Canada
| | - Mitesh Borad
- Division of Hematology and Medical Oncology, Mayo Clinic Hospital, Phoenix, AZ, United States
| | - Tushar C. Patel
- Department of Transplantation and Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
| | - Terry M. Therneau
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN 55905, United States
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Huang S, Song JL, Li B, Yi PS, Yang J. Should lymphadenectomy performed routinely in patients with primary intrahepatic cholangiocarcinoma undergoing curative hepatectomy? A retrospective cohort study with propensity-score matching analysis. BMC Surg 2023; 23:364. [PMID: 38036995 PMCID: PMC10688469 DOI: 10.1186/s12893-023-02255-5] [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: 11/07/2022] [Accepted: 11/02/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND The benefit of routine lymphadenectomy (LD) in improving outcomes for patients with primary intrahepatic cholangiocarcinoma (ICC) undergoing curative hepatectomy remains unclear. MATERIALS AND METHODS This study enrolled 269 consecutive patients who underwent liver resection for primary ICC from January 2009 to July 2020 in West China Hospital. The association of the nodal status with disease-free survival (DFS) and overall survival (OS) was analyzed using the Cox proportional hazards model and 1:1 propensity score matching (PSM) analysis. RESULTS Seventy-five (27.9%) patients underwent curative liver resection combined with LD (LD+ group), while 194 (72.1%) patients received curative liver resection without LD (LD- group and Nx group). Among the LD+ group, metastatic disease was present in 36 patients (48%, N1 group) and absent in 39 patients (N0 group). During the follow-up period, 116 patients (43.1%) experienced tumor recurrence and 101 patients (37.5%) died due to recurrence. Multivariate analysis revealed that lymph node metastasis (N1, HR 3.682, 95% CI 1.949-6.957, p < 0.001) was associated with worse OS, while LD+ status (HR 0.504, 95% CI 0.298-0.853, p = 0.011) was associated with improved OS. Adjuvant therapy was a protective factor for both DFS (HR 0.602, 95% CI, 0.447-0.810, p = 0.001) and OS (HR 0.683, 95% CI 0.484-0.963, p = 0.030). After 1:1 PSM, the LD+ patients (n = 74) displayed similar 1-, 3- and 5-year DFS rates (40.0, 7.9 and 7.9% vs. 29.0, 13.7 and 13.7%, p = 0.741) and OS rates (56.0, 26.6 and 22.2% vs. 58.9, 25.6, and 16.4%, p = 0.644) to the LD- patients (n = 74). Additionally, among the 75 LD+ patients, 48 patients underwent hepatic hilar lymphadenectomy (HHL), and 27 patients underwent extended hepatic hilar lymphadenectomy (EHL). Both DFS (p = 0.504) and OS (p = 0.215) were similar between the HHL and EHL groups. CONCLUSION Routine LD and adjuvant therapy may contribute to improved OS according to the crude analysis. LD could provide accurate staging without excessive risk and guide adjuvant therapy based on the tumor stage, potentially resulting in better survival. These results suggest that a routine LD should be considered during curative hepatectomy for ICC.
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Affiliation(s)
- Shan Huang
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Sichuan Province, Chengdu, 610072, China
| | - Jiu-Lin Song
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Bo Li
- Department of Vascular Surgery, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Peng-Sheng Yi
- Affiliated Hospital of North Sichuan Medical College, Sichuan Province, the Nanchong City, China
| | - Jian Yang
- Department of Liver Transplantation Center, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China.
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Dhote A, Tzedakis S, Shapira OI, Nassar A, Boudjema K, Fuks D. Current status and perspectives in the surgical and oncological management of intrahepatic cholangiocarcinoma. J Visc Surg 2023; 160:346-355. [PMID: 37563006 DOI: 10.1016/j.jviscsurg.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor after hepatocellular carcinoma (HCC). Management depends on their resectability at the time of diagnosis. Two types can be distinguished by imaging: resectable ICCs amenable to surgery and locally advanced and/or metastatic ICCs, that are treated by chemotherapy, radiotherapy or loco-regional treatment (radioembolization, chemoembolization, intra-arterial chemotherapy and thermoablation). Over the last decade, the management strategy for these tumors has been modified by the appearance of loco-regional treatments as well as the introduction of immunotherapy that have shown their efficacy in the control of ICC. The aim of this review is to describe the current status of treatments for ICCs, as well as the different therapeutic strategies being assessed.
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Affiliation(s)
- Alix Dhote
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris-Sorbonne University, Paris, France
| | - Stylianos Tzedakis
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France
| | - Ortal Itzaki Shapira
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France
| | - Alexandra Nassar
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France
| | - Karim Boudjema
- Hepatobiliary and Digestive Surgery Department, Pontchaillou Hospital, Rennes 1 University, Rennes, France
| | - David Fuks
- AP-HP, Cochin Port Royal Hospital Group, DMU Cancerology and medical-surgical specialties, Digestive, Hepatobiliary and Endocrine Surgery Department, Paris, France; Paris Cité University, Paris, France.
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Zhang X, Zhu WY, Shen SY, Shen JH, Chen XD. Biological roles of RNA m7G modification and its implications in cancer. Biol Direct 2023; 18:58. [PMID: 37710294 PMCID: PMC10500781 DOI: 10.1186/s13062-023-00414-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/07/2023] [Indexed: 09/16/2023] Open
Abstract
M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research's future directions and trends.
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Affiliation(s)
- Xin Zhang
- Department of Dermatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
| | - Wen-Yan Zhu
- Department of Dermatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
| | - Shu-Yi Shen
- Department of Dermatology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jia-Hao Shen
- Department of Dermatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
| | - Xiao-Dong Chen
- Department of Dermatology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
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12
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Zhang Z, Wang X, Li H, Sun H, Chen J, Lin H. Case Report: Camrelizumab combined with gemcitabine and oxaliplatin in the treatment of advanced intrahepatic cholangiocarcinoma: a case report and literature review. Front Immunol 2023; 14:1230261. [PMID: 37671157 PMCID: PMC10475830 DOI: 10.3389/fimmu.2023.1230261] [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: 05/28/2023] [Accepted: 08/08/2023] [Indexed: 09/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the most common invasive malignant tumors, with a 5-year survival rate of less than 5%. Currently, radical surgical resection is the preferred treatment for ICC. However, most patients are only diagnosed at an advanced stage and are therefore not eligible for surgery. Herein, we present a case of advanced ICC in which radical surgery was not possible due to tumor invasion of the second porta hepatis and right hepatic artery. Six treatment cycles with a gemcitabine and oxaliplatin (GEMOX) regimen combined with camrelizumab immunotherapy achieved a partial response and successful tumor conversion, as tumor invasion of the second porta hepatis and right hepatic artery was no longer evident. The patient subsequently underwent successful radical surgical resection, including hepatectomy, caudate lobe resection, and cholecystectomy combined with lymph node dissection. Cases of patients with advanced ICC undergoing surgical resection after combined immunotherapy and chemotherapy are rare. The GEMOX regimen combined with camrelizumab demonstrated favorable antitumor efficacy and safety, suggesting that it might be a potential feasible and safe conversion therapy strategy for patients with advanced ICC.
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Affiliation(s)
- Zhongyan Zhang
- Department of Hepatobiliary Surgery, Weifang People’s Hospital, Weifang, China
| | - Xin Wang
- Department of Hepatobiliary Surgery, Weifang People’s Hospital, Weifang, China
| | - Hehe Li
- Department of Geriatrics, Weifang People’s Hospital, Weifang, China
| | - Huimin Sun
- Department of Pathology, Weifang People’s Hospital, Weifang, China
| | - Jianhong Chen
- Department of Hepatobiliary Surgery, Weifang People’s Hospital, Weifang, China
| | - Hongfeng Lin
- Department of Hepatobiliary Surgery, Weifang People’s Hospital, Weifang, China
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13
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Liao S, Liao R, Wu H, Wang S, Zhou Y. Proposal for a new N-stage classification system for intrahepatic cholangiocarcinoma. Front Oncol 2023; 13:1149211. [PMID: 37637053 PMCID: PMC10455933 DOI: 10.3389/fonc.2023.1149211] [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: 01/21/2023] [Accepted: 06/22/2023] [Indexed: 08/29/2023] Open
Abstract
Background The number of metastatic lymph nodes (MLNs) is not considered in the nodal status (N classification) of intrahepatic cholangiocarcinoma (ICC) in the current 8thEdition of the American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to find out the optimal cut-off point based on the number of MLNs and establish a modified AJCC staging system for ICC according to the new N category. Methods A total of 675 ICC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. The optimal cut-off value of MLNs affecting survival was determined by X-tile software. The relative discriminative power was assessed by Harrell's concordance index (C-index) and Akaike information criterion (AIC). Results The proposed new nodal category subdivided patients into three groups (N0, no MLN; N1, 1-3 MLNs; and N2, ≥ 4 MLNs) with significantly different overall survival (P < 0.001). Multivariable analysis revealed that the new nodal category was an independent prognostic factor (P < 0.001). Both the C-index and AIC for our modified staging system were better than those for the 8th AJCC edition (0.574 [95% confidence interval 0.533-0.615] versus 0.570 [95% confidence interval 0.527-0.613], and 853.30 versus 854.21, respectively). Conclusion The modified AJCC staging system based on the number of MLNs may prove to be a useful alternative for predicting survival of ICC patients in clinical practice.
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Affiliation(s)
- Shan Liao
- Department of General Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Ruizhe Liao
- Department of General Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Huaxing Wu
- Department of General Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Shijie Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Yanming Zhou
- Department of General Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
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14
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Zhao C, Li X, Luo L, Chen C, He C. Modified staging system of positive lymph nodes based nomogram in intrahepatic cholangiocarcinoma. Cancer Cell Int 2023; 23:148. [PMID: 37516863 PMCID: PMC10386250 DOI: 10.1186/s12935-023-03005-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 07/26/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram. METHOD Clinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort. RESULTS In those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P < 0.0001). Moreover, there was a significant correlation between the new PLN classification and adverse clinical characteristic including Micro Invasion (P = 0.001), Lymph Vessel Invasion (P = 0.040), Satellite Sites (P < 0.001), and Tumor Size (P = 0.005). The PLN and ELN were both independent prognostic factors for survival outcomes in the multivariate analysis, and further showed large contribution to the nomogram. The nomogram achieved a satisfied C-index of 0.813 for overall survival (OS), 0.869 for progression-free survival (PFS) in the primary cohort, and 0.787 for OS, 0.762 for PFS in the validation cohort. CONCLUSION The modified classification of PLN in iCCA could accurately stratify the N1 stage patients in 8th TNM staging system into two groups with significantly different overall survival. The development of this nomogram can offer new evidence to precisely post-operative management of iCCA patients.
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Affiliation(s)
- Chongyu Zhao
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Army Medical University, Chongqing, P. R. China
| | - Xiyuan Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Li Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Cheng Chen
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, P. R. China
| | - Chaobin He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
- Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
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Sun D, Xu Z, Cao S, Wu H, Lu M, Xu Q, Wang K, Ji G. Imaging features based on CT and MRI for predicting prognosis of patients with intrahepatic cholangiocarcinoma: a single-center study and meta-analysis. Cancer Imaging 2023; 23:56. [PMID: 37287062 PMCID: PMC10245452 DOI: 10.1186/s40644-023-00576-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 05/22/2023] [Indexed: 06/09/2023] Open
Abstract
BACKGROUND To evaluate the prognostic role of imaging features based on CT and MRI in intrahepatic cholangiocarcinoma (ICC). METHODS Two hundred and four patients from a single-center database who underwent radical ICC surgery from 2010 to 2019 were enrolled in the study. Cox proportional hazard model was used for survival analysis of imaging features. A meta-analysis was performed to determine imaging features that predict overall survival (OS) and event-free survival (EFS) in ICC. RESULTS In the CT group of the retrospective cohort, tumor multiplicity, infiltrative tumor margin, lymph node metastasis, enhancement pattern in hepatic arterial phase and tumor necrosis correlated with poorer EFS and OS; moreover, enhancing capsules, high carcinoembryonic antigen levels contributed to poor OS. In the MRI group, tumor multiplicity and enhancement pattern were prognostic factors for OS; tumor multiplicity and enhancement pattern resulted in poor EFS. A total of 13 articles containing 1822 patients with ICC were enrolled in the adjusted hazard ratios meta-analysis. The results showed that enhancement pattern and infiltrative tumor margin were predictors of OS and EFS, whereas bile duct invasion was a predictor of OS. CONCLUSIONS Arterial enhancement patterns and tumor margin status were associated with both OS and EFS of ICC patients following resection.
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Affiliation(s)
- Dongwei Sun
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China
| | - Zhenggang Xu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China
| | - Shuya Cao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China
| | - Huaiyu Wu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China
| | - Ming Lu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Jiangsu Province, China
| | - Qing Xu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Jiangsu Province, China
| | - Ke Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China.
| | - Guwei Ji
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
- NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, 300 Guangzhou RoadJiangsu Province, Nanjing, People's Republic of China.
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Moazzam Z, Alaimo L, Endo Y, Lima HA, Ruzzenente A, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Cloyd J, Ejaz A, Pawlik TM. Combined Tumor Burden Score and Carbohydrate Antigen 19-9 Grading System to Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma. J Am Coll Surg 2023; 236:804-813. [PMID: 36728327 DOI: 10.1097/xcs.0000000000000557] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The interplay of carbohydrate antigen 19-9 (CA19-9) and tumor burden score (TBS) within intrahepatic cholangiocarcinoma remains ill-defined. We evaluated the roles of TBS and CA19-9 relative to overall survival (OS) and recurrence, as well as the predictive ability of the combined TBS and CA19-9 (CTC) grading system. STUDY DESIGN Patients undergoing liver resection for intrahepatic cholangiocarcinoma between 2000 and 2020 were identified using a multi-institutional database. The impact of CA19-9 and TBS on 5-year OS and 3-year recurrence was assessed, along with the prognostic accuracy of the CTC grading system (ie the composite score of CA19-9 level and TBS). RESULTS Among 831 patients, the median age was 58.2 years and 482 (58.0%) were male. The median [IQR] CA19-9 level was 49.7 [17.0, 221.0] U/mL and TBS was 6.1 [4.1, 8.3]. Median [IQR] and 5-year OS were 36.9 [32.3, 43.1] months and 38.9%, respectively; 3-year recurrence was 68.9%. Five-year survival varied relative to CA19-9 (low vs high, 49.0% vs 19.7%) and TBS (low vs high, 53.6% vs 26.9%) (p < 0.001 for both). On multivariable analysis, high CA19-9 (hazard ratio [HR] 2.02, 95% CI 1.64 to 2.49) and high TBS (HR 1.64, 95% CI 1.32 to 2.06) remained independently associated with OS. In turn, the CTC grading score stratified 5-year OS (low vs intermediate vs high CTC, 57.7% vs 39.9% vs 12.6%; p < 0.001) and remained an independent prognostic factor (referent, low CTC; [intermediate CTC] HR 1.54, 95% CI 1.18 to 2.01; [high CTC] HR 3.28, 95% CI 2.47 to 4.36). CONCLUSIONS The interplay between tumor morphology and biology dictates long-term prognosis after liver resection for intrahepatic cholangiocarcinoma. Prognostic models such as the CTC grading system may inform discussions around prognosis, as well as help identify which patients with ICC may benefit more from neoadjuvant chemotherapy rather than up-front surgery.
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Affiliation(s)
- Zorays Moazzam
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Laura Alaimo
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Yutaka Endo
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Henrique A Lima
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Andrea Ruzzenente
- Department of Surgery, University of Verona, Verona, Italy (Ruzzenente, Guglielmi)
| | - Alfredo Guglielmi
- Department of Surgery, University of Verona, Verona, Italy (Ruzzenente, Guglielmi)
| | - Luca Aldrighetti
- Department of Surgery, Ospedale San Raffaele, Milan, Italy (Aldrighetti)
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD (Weiss)
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA (Bauer)
| | - Sorin Alexandrescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania (Alexandrescu)
| | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal (Marques)
| | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada (Martel)
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia (Pulitano)
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China (Shen)
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France (Cauchy)
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands (Koerkamp)
| | - Itaru Endo
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan (Endo)
| | - Jordan Cloyd
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Aslam Ejaz
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
| | - Timothy M Pawlik
- From the Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH (Moazzam, Alaimo, Endo, Lima, Cloyd, Ejaz, Pawlik)
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17
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Survival Benefit of Surgical Treatment for Elderly Patients with Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Study in the SEER Database by Propensity Score Matching Analysis. Curr Oncol 2023; 30:2642-2652. [PMID: 36975414 PMCID: PMC10047145 DOI: 10.3390/curroncol30030201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/17/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023] Open
Abstract
Despite a rising trend in intrahepatic cholangiocarcinoma (ICC) incidence in the elderly population worldwide, the benefit of surgery for those patients is still controversial. Data from 811 elderly patients diagnosed with non-metastatic ICC were obtained from the US surveillance, epidemiology, and end results (SEER) program database. Propensity score matched (PSM) was conducted for the better balance of baseline. The associations between tumor characteristics and surgery with overall survival (OS) and cancer specific survival (CSS) were estimated using hazard ratios (HR) and 95% confidence intervals (CI). The results showed that ICC patients above 60 years old taking surgery had better OS (hazard ratio [HR], 0.258; 95% CI, 0.205–0.324) and CSS (hazard ratio [HR], 0.239; 95% CI, 0.188–0.303) than patients without surgery. Similar trends in patients above 65 years old, above 70 years old, above 75 years old, and above 80 years old were observed, separately. This benefit was also showed in lymph node-negative (N0) and lymph node-positive (N1) subgroups and N0 patients are more likely to take an advantage from surgery than N1 patients. The different outcomes between surgery and non-surgery suggest that surgical treatment may be recommended for elderly ICC if the tumor is resectable to ensure optimal treatment.
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18
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Sumiyoshi T, Uemura K, Shintakuya R, Okada K, Otsuka H, Serikawa M, Ishii Y, Tsuboi T, Arihiro K, Takahashi S. A case of unresectable locally advanced intrahepatic cholangiocarcinoma that achieved pathological complete response after gemcitabine and S1 chemotherapy. Clin J Gastroenterol 2022; 15:1164-1168. [DOI: 10.1007/s12328-022-01700-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/04/2022] [Indexed: 11/27/2022]
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19
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Wang Y, Strazzabosco M, Madoff DC. Locoregional Therapy in the Management of Intrahepatic Cholangiocarcinoma: Is There Sufficient Evidence to Guide Current Clinical Practice? Curr Oncol Rep 2022; 24:1741-1750. [PMID: 36255606 PMCID: PMC10878124 DOI: 10.1007/s11912-022-01338-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2022] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW Intrahepatic cholangiocarcinoma (iCCA) carries a dismal prognosis and, despite increasing incidence, still lacks effective treatments. In this scenario, locoregional therapies (LRT) are gaining interest as they may be effective at local tumor control and complementary to surgical and non-surgical approaches. In this article, we will review the evolving role of LRT performed by interventional radiologists in the management of iCCA. RECENT FINDINGS Accumulating retrospective evidence indicates that ablative therapies and transarterial embolizations are of benefit for iCCA with unresectable disease, demonstrating promising safety profiles and prolonged or comparable survival outcomes compared to systemic therapy and surgery. Additionally, for surgical candidates, portal ± hepatic venous embolization can improve the safety of hepatectomy by inducing preoperative hypertrophy of the non-involved liver lobe. LRTs are playing an increasingly important role in the multimodal treatment of iCCA from various perspectives with reduced toxicity relative to traditional treatments. To expand the scope of applications for LRTs in this setting, future prospective randomized studies are needed to confirm their efficacy and advantage.
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Affiliation(s)
- Yifan Wang
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
| | - Mario Strazzabosco
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - David C Madoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA.
- Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
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20
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Yu Z, Ni Q, Jia H, Gao H, Yang F, Zhu H, Liu F, Wang J, Zhou X, Chang H, Lu J. Prognostic analysis of radical resection for iCCA phl and iCCA pps: A retrospective cohort study. Front Oncol 2022; 12:992606. [PMID: 36479069 PMCID: PMC9721347 DOI: 10.3389/fonc.2022.992606] [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: 08/12/2022] [Accepted: 10/24/2022] [Indexed: 11/07/2023] Open
Abstract
BACKGROUD At present, there is no definitive conclusion about the relative prognostic factors on intrahepatic cholangiocarcinoma perihilar large duct type (iCCAphl) and iCCA peripheral small duct type (iCCApps). AIM OF THE STUDY To compare the prognoses of two different types of iCCA, and identify the independent risk factors affecting the long-term survival of patients undergoing radical resection for iCCA. METHODS This study included 89 patients with iCCA who underwent radical resection at the Department of Hepatobiliary Surgery of the East Yard of the Shandong Provincial Hospital between January 2013 and March 2022. According to the tumor origin, these patients were divided into the iCCAphl group (n = 37) and iCCApps group (n = 52). The prognoses of the two groups were compared using Kaplan-Meier analysis, whereas the independent risk factors of their prognoses were identified using Cox univariate and multivariate regression analyses. RESULTS In the iCCApps group, the independent risk factors for overall survival included diabetes history (p = 0.006), lymph node metastasis (p = 0.040), and preoperative carbohydrate antigen 19-9 (p = 0.035). In the iCCAphl group, the independent risk factors for overall survival included multiple tumors (p = 0.010), tumor differentiation grade (p = 0.008), and preoperative jaundice (p = 0.009). CONCLUSIONS Among the iCCA patients who underwent radical resection, the long-term prognosis of iCCApps maybe better than that of iCCAphl. The prognoses of these two types of iCCA were affected by different independent risk factors.
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Affiliation(s)
- Zetao Yu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Qingqiang Ni
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hongtao Jia
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hengjun Gao
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Faji Yang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Huaqiang Zhu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Fangfeng Liu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jianlu Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xu Zhou
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hong Chang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jun Lu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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21
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Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision. Cancers (Basel) 2022; 14:cancers14205074. [PMID: 36291857 PMCID: PMC9600404 DOI: 10.3390/cancers14205074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/09/2022] [Accepted: 10/12/2022] [Indexed: 11/30/2022] Open
Abstract
Simple Summary Cholangiocarcinoma is a relatively rare but deadly disease with traditionally limited treatment options. The disease can be categorized by anatomic location within the biliary tree, with different associated risk factors and molecular profiles. Recent years have seen a burgeoning of targeted therapies that have enhanced survival in subsets of patients with certain mutations. We herein discuss these more recent advances as well as providing an overview of more well-known treatment modalities, with the goal of providing an accessible source for practicing clinicians. Abstract A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated with a median overall survival (OS) of 40 months, this number drastically decreases for unresectable advanced cholangiocarcinoma (CCA), which is treated with systemic therapy. The first-line chemotherapy regimen of gemcitabine and cisplatin is associated with a median overall survival of only 11.7 months. Since the Food and Drug Administration (FDA)’s approval of the isocitrate dehydrogenase (IDH) 1 inhibitor ivosidenib in August 2021, there has been increasing interest in targeted therapy for CCA patients harboring mutations in fibroblast growth factor receptor (FGFR) 2, neurotrophic receptor tyrosine kinase (NTRK), B-raf kinase (BRAF), and HER2. At the same time, immunotherapy with immune checkpoint inhibitors isalso being used in relapsed CCA. This review looks into the most recently completed and ongoing studies of targeted therapy as monotherapy or in combination with chemo- and/or immunotherapy. Whether it is resection, liver transplant, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or any combination of these treatment modalities, great strides are being made to improve outcomes for this challenging disease.
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22
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Li H, Liu R, Li J, Li J, Wu H, Wang G, Li D. Tumor location influences perioperative and oncologic outcomes in solitary intrahepatic cholangiocarcinoma following curative resection: a multi-center analysis. HPB (Oxford) 2022; 24:1543-1550. [PMID: 35393220 DOI: 10.1016/j.hpb.2022.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 01/13/2022] [Accepted: 03/14/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND To compare perioperative and oncologic outcomes of patients with different locations of intrahepatic cholangiocarcinoma (ICC). METHODS A total of 352 ICC patients underwent curative intent hepatectomy were included. Clinical outcomes were compared between ICC patients with tumors located at subcapsular and non-subcapsular, perihepatic vein (pHV) and non-pHV, or periportal vein (pPV) and non-pPV. Kaplan-Meier curves were used to evaluate the influence of tumor location on survival outcomes. RESULTS Surgical procedures for pPV ICC were associated with longer operative time and elevated intraoperative blood loss compared to non-pPV. Patients with pPV ICC significantly correlated to increased frequency of log odds of positive lymph nodes (LODDS) classification 3-4. In addition, the ICC located at pPV was correlated with both worse overall survival (OS) and disease-free survival (DFS) compared to non-pPV, whereas no significant difference was observed between subcapsular and non-subcapsular or between pHV and non-pHV. CONCLUSIONS A pPV location contributed to poor perioperative outcomes and quick tumor recurrence for patients with solitary ICC undergoing curative resection. A pPV location also contributed to regional lymph node metastases and was a risk factor for intrahepatic recurrence. Subcapsular and pHV locations did not influence clinical outcomes of ICC patients.
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Affiliation(s)
- Hui Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Rongqiang Liu
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Jiawang Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Jiaxin Li
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Wu
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510006, China.
| | - Dewei Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China.
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23
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Zhou SN, Lu SS, Ju DW, Yu LX, Liang XX, Xiang X, Liangpunsakul S, Roberts LR, Lu YY, Zhang N. A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma. J Clin Transl Hepatol 2022; 10:254-262. [PMID: 35528972 PMCID: PMC9039701 DOI: 10.14218/jcth.2021.00099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/18/2021] [Accepted: 06/12/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy that causes a poor survival. We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages. METHODS A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled. Subjects were followed for survival status until June 30, 2020. A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model, and was then validated in the validation cohort. RESULTS The median age was 55 years. With a median follow-up of 50.4 months, 337 patients died. The median survival was 11.6 months, with 1-, 3- and 5-year survival rates of 48.3%, 22.7% and 16.2%, respectively. Factors associated with overall survival were multiple tumors, lymph node involvement, vascular invasion, distant metastasis, decreased albumin, elevated lactate dehydrogenase (LDH), decreased iron, elevated fibrinogen, elevated CA125 and elevated CA19-9. A nomogram predicting survival of ICC patients at the time of diagnosis achieved a Harrel's c-statistic of 0.758, significantly higher than the 0.582 of the TNM stage alone. Predicted median survivals of those within the low, mid and high-risk subgroups were 35.6, 12.1 and 6.2 months, respectively. CONCLUSIONS A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC. Further studies are needed to validate the prognostic capability of our new model.
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Affiliation(s)
- Shuang-Nan Zhou
- Department of Infectious Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shan-Shan Lu
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Da-Wei Ju
- Central Theater Command General Hospital of The Chinese People’s Liberation Army, Wuhan, Hubei, China
| | - Ling-Xiang Yu
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiao-Xiao Liang
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Beijing Chaoyang Integrative Medicine Emergency Medical Center, Beijing, China
| | - Xiao Xiang
- BeiGene (Beijing) Co. Ltd, Beijing, China
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, IN, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Yin-Ying Lu
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Correspondence to: Ning Zhang and Yinying Lu,, Department of Liver Disease, the Fifth Medical Center, Chinese PLA General Hospital, Beijing 100039, China. ORCID: https://orcid.org/0000-0002-6826-9175 (NZ). Tel: +86-10-66949711 (NZ) and +86-10-66933380 (YL), E-mail: (NZ) and (YL)
| | - Ning Zhang
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Correspondence to: Ning Zhang and Yinying Lu,, Department of Liver Disease, the Fifth Medical Center, Chinese PLA General Hospital, Beijing 100039, China. ORCID: https://orcid.org/0000-0002-6826-9175 (NZ). Tel: +86-10-66949711 (NZ) and +86-10-66933380 (YL), E-mail: (NZ) and (YL)
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24
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Rhee H, Choi SH, Park JH, Cho ES, Yeom SK, Park S, Han K, Lee SS, Park MS. Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma. Liver Int 2022; 42:930-941. [PMID: 35152534 DOI: 10.1111/liv.15196] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS As most staging systems for intrahepatic cholangiocarcinoma (iCCA) are based on pathological results, preoperative prognostic prediction is limited. This study aimed to develop and validate a prognostic model for the overall survival of patients with mass-forming iCCA (MF-iCCA) using preoperative magnetic resonance imaging (MRI) and clinical findings. METHODS We enrolled a total of 316 patients who underwent preoperative MRI and surgical resection for treatment-naive MF-iCCA from six institutions, between January 2009 and December 2015. The subjects were randomly assigned to a training set (n = 208) or validation set (n = 108). The MRIs were independently reviewed by three abdominal radiologists. Using MRI and clinical findings, an MRI prognostic score was established. We compared the discrimination performance of MRI prognostic scores with those of conventional pathological staging systems. RESULTS We developed an MRI prognostic score consisting of serum CA19-9 and three MRI findings (tumour multiplicity, lymph node metastasis and bile duct invasion). The MRI prognostic score demonstrated good discrimination performance in both the training set (C-index, 0.738; 95% confidence interval [CI], 0.698-0.780) and validation set (C-index, 0.605; 95% CI, 0.526-0.680). In the validation set, MRI prognostic score showed no significant difference with AJCC 8th TNM stage, MEGNA score and Nathan's stage. CONCLUSIONS Our MRI prognostic score for overall survival of MF-iCCA showed comparable discriminatory performance with pathological staging systems and might be used to determine an optimal treatment strategy.
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Affiliation(s)
- Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine Seoul, Seoul, Republic of Korea
| | - Suk-Keu Yeom
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Kyunghwa Han
- Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, College of Medicine, Yonsei University, Seoul, South Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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25
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Manzia TM, Parente A, Lenci I, Sensi B, Milana M, Gazia C, Signorello A, Angelico R, Grassi G, Tisone G, Baiocchi L. Moving forward in the treatment of cholangiocarcinoma. World J Gastrointest Oncol 2021; 13:1939-1955. [PMID: 35070034 PMCID: PMC8713313 DOI: 10.4251/wjgo.v13.i12.1939] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/14/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.
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Affiliation(s)
- Tommaso M Manzia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Alessandro Parente
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Ilaria Lenci
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Bruno Sensi
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Carlo Gazia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | | | - Roberta Angelico
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Giuseppe Grassi
- Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
| | - Giuseppe Tisone
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
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Hwang S, Jung DH, Jwa EK, Kim Y. Preemptive pyloroplasty for iatrogenic vagus nerve injury in intrahepatic cholangiocarcinoma patients undergoing extensive left-sided lymph node dissection. Yeungnam Univ J Med 2021; 39:235-243. [PMID: 34902957 PMCID: PMC9273145 DOI: 10.12701/yujm.2021.01550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/17/2021] [Indexed: 11/14/2022] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) of the left liver often shows left-sided lymph node (LN) metastasis. If gastric lesser curvature is extensively dissected, it can induce an iatrogenic injury to the extragastric vagus nerve branches that control motility of the pyloric sphincter and lead to gastric stasis. To cope with such LN dissection-associated gastric stasis, we performed pyloroplasty preemptively. The objective of this study was to analyze our 20-year experience of preemptive pyloroplasty performed in 10 patients. Methods We investigated clinical sequences of 10 patients with ICC who underwent preemptive pyloroplasty following left hepatectomy and extended left-sided LN dissection. Incidence of gastric stasis and oncological survival outcomes were analyzed. Results All 10 patients were classified as stage IIIB due to T1-3N1M0 stage according to the 8th edition of American Joint Committee on Cancer staging system. The overall patient survival rate was 51.9% at 1 year, 25.9% at 2 years, and 0% at 3 years. Seven patients showed uneventful postoperative recovery after surgery. Two patients suffered from gastric stasis, which was successfully managed with supportive care. One patient suffered from overt gastric paresis, which was successfully managed with azithromycin administration for 1 month. Conclusion We believe that preemptive pyloroplasty is an effective surgical option to prevent gastric stasis in patients undergoing extensive left-sided LN dissection. Azithromycin appears to be a potent prokinetic agent in gastroparesis.
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Affiliation(s)
- Shin Hwang
- Division of Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun-Kyoung Jwa
- Division of Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yumi Kim
- Division of Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Hewitt DB, Brown ZJ, Pawlik TM. Surgical management of intrahepatic cholangiocarcinoma. Expert Rev Anticancer Ther 2021; 22:27-38. [PMID: 34730474 DOI: 10.1080/14737140.2022.1999809] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) incidence continues to rise worldwide, and overall survival remains poor. Complete surgical resection remains the only opportunity for cure in patients with ICC yet only one-third of patients present with resectable disease. AREAS COVERED While the low incidence rate of ICC hinders accrual of patients to large, randomized control trials, larger database and long-term institutional studies provide evidence to guide surgical management of ICC. These studies demonstrate feasibility, safety, and efficacy of aggressive surgical management in appropriately selected patients with ICC. Recent advances in the management of ICC, with a focus on surgical considerations, are reviewed. EXPERT OPINION Historically, little progress has been made in the management of ICC with stagnant mortality rates and poor long-term outcomes. However, regionalization of care to centers with experienced multidisciplinary teams, advances in minimally invasive surgical techniques, discovery and development of targeted and immunotherapy agents, and combination locoregional and systemic therapies offer signs of progress in the management of ICC.
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Affiliation(s)
- D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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28
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Rao B, Ren T, Wang X, Wang H, Zou Y, Sun Y, Liu S, Ren Z, Yu Z. Dysbiosis in the Human Microbiome of Cholangiocarcinoma. Front Physiol 2021; 12:715536. [PMID: 34867436 PMCID: PMC8633309 DOI: 10.3389/fphys.2021.715536] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignant tumor of the biliary system with a very poor prognosis. The human microbiome, which is the sum of the genetic information of human microorganisms, plays an important role in regulating the digestion, absorption, immune response, and metabolism of the host. Increasing evidence indicates a close relationship between CCA and the human microbiome. Specific alterations occur in the human microbiome of patients with CCA. Therefore, in this review, we aimed to summarize the recent evidence on dysbiosis in the human microbiome of CCA. Then, we generalized the effect of Helicobacter pylori on CCA. Additionally, the potential mechanism of human microbial dysbiosis promoted the progress of CCA, and its precancerous disease was also explored. Furthermore, the possibility of the human microbiome as a diagnostic and therapeutic target of CCA was discussed.
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Affiliation(s)
- Benchen Rao
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tong Ren
- Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuemei Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haiyu Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yawen Zou
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Sun
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shanshuo Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zujiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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29
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Serifis N, Tsilimigras DI, Cloonan DJ, Pawlik TM. Challenges and Opportunities for Treating Intrahepatic Cholangiocarcinoma. Hepat Med 2021; 13:93-104. [PMID: 34754247 PMCID: PMC8572023 DOI: 10.2147/hmer.s278136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/22/2021] [Indexed: 12/29/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.
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Affiliation(s)
- Nikolaos Serifis
- Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA
| | | | - Daniel J Cloonan
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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30
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Liang J, Zhou H, Huang XQ, Liu YF, Zhang L, He D, Cui Y, Guo J, Hu K, Wu C. A Myeloid Signature-Based Nomogram Predicts the Postoperative Recurrence of Intrahepatic Cholangiocarcinoma. Front Mol Biosci 2021; 8:742953. [PMID: 34722632 PMCID: PMC8548627 DOI: 10.3389/fmolb.2021.742953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/23/2021] [Indexed: 11/24/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common cancer in liver, with a high recurrence rate after surgery. Recently, we identified a CD11b-CD169-based myeloid response score (MRS), which showed remarkable prognostic potential in hepatocellular carcinoma (HCC). Here, we aimed to verify the prognostic value of the MRS in iCCA and establish an MRS-based nomogram to predict the postoperative prognosis of iCCA patients. From April 2005 to March 2017, a total of 84 patients from the Third Affiliated Hospital of Sun Yat-sen University were enrolled. Preoperative clinical information and surgical specimens of enrolled patients were collected. Among these, tissues from 75 patients passed the clinical data quality control and the staining quality control. The protein expression of CD11b and CD169 in iCCA samples were detected by immunohistochemistry (IHC). Kaplan-Meier analysis and receiver operating characteristic (ROC) curves revealed that the MRS had a high discriminatory ability for predicting the time to recurrence (TTR) of iCCA patients after surgery. Three independent risk factors selected by a Cox proportional hazards regression analysis, namely, the MRS, the tumor size and the status of vascular invasion, were included to construct a nomogram to predict the recurrence of iCCA after resection surgery. ROC curves, calibration analysis and decision curve analysis (DCA) suggested that this nomogram had notable discriminatory power, stability and clinical usefulness in predicting the postoperative recurrence. Together, we explored the prognostic value of the MRS in iCCA, and constructed an MRS-based nomogram which may help to predict postoperative recurrence and aid clinical decisions for iCCA patients.
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Affiliation(s)
- Jing Liang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Zhou
- Department of General Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Gastrointestinal Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiang-Qi Huang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yan-Fei Liu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Lei Zhang
- Department of Biliary-Pancreatic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dan He
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongmei Cui
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jinrui Guo
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Kunpeng Hu
- Department of General Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chong Wu
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
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31
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Zhang XF, Xue F, He J, Alexandrescu S, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Koerkamp BG, Itaru E, Lv Y, Pawlik TM. Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma. HPB (Oxford) 2021; 23:1456-1466. [PMID: 33814298 DOI: 10.1016/j.hpb.2021.02.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/14/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. METHODS Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM). RESULTS The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p < 0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p < 0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases. CONCLUSION The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - Oliver Soubrane
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Guillaume Martel
- Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | - Bas G Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Endo Itaru
- Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan
| | - Yi Lv
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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32
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Sutton TL, Billingsley KG, Walker BS, Fung AW, Maynard E, Enestvedt CK, Dewey EN, Brinkerhoff BT, Lopez CD, Orloff SL, Mayo SC. Detection of Tumor Multifocality in Resectable Intrahepatic Cholangiocarcinoma: Defining the Optimal Pre-operative Imaging Modality. J Gastrointest Surg 2021; 25:2250-2257. [PMID: 33565011 DOI: 10.1007/s11605-021-04911-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/09/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Multiple tumor foci (MTF) in intrahepatic cholangiocarcinoma (ICC), including satellitosis and true multifocality, is a known negative prognostic factor and can inform pre-operative decision-making. Lack of standardized pre-operative liver staging practices may contribute to undiagnosed MTF and poor outcomes. We sought to investigate the sensitivity of different cross-sectional imaging modalities for MTF at our institution. METHODS We identified n = 52 patients with ICC who underwent curative-intent resection from 2004 to 2017 in a multidisciplinary hepato-pancreato-biliary cancer program. Timing and modality of pre-operative imaging were recorded. Blinded review of imaging was performed and modalities were evaluated for false-negative rate (FNR) in detecting MTF, satellitosis, and true multifocality. RESULTS Forty-one (79%) patients underwent CT and 20 (38%) underwent MRI prior to hepatectomy. MTF was pre-operatively identified in six (12%) patients. An additional seven patients had MTF discovered on final surgical pathology, despite a median interval from CT/MRI to surgery of 20 days. On blinded review the FNR of MRI compared to CT for multifocality was 0% vs. 38%, 50% vs 80% for satellitosis, and 22% vs 46% for MTF as a whole. CONCLUSION CT is inadequate for pre-operative diagnosis of MTF in resectable ICC, even when performed within 30 days of hepatectomy. We recommend liver-protocol MRI as the standard pre-operative imaging modality in non-metastatic ICC.
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Affiliation(s)
- Thomas L Sutton
- Department of Surgery, Division of Surgical Oncology, Oregon Heath & Science University (OHSU), 3181 SW Sam Jackson Park Rd, Mail Code: L-619, Portland, OR, 97239, USA
| | - Kevin G Billingsley
- Department of Surgery, Division of Surgical Oncology, Oregon Heath & Science University (OHSU), 3181 SW Sam Jackson Park Rd, Mail Code: L-619, Portland, OR, 97239, USA.,The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA
| | - Brett S Walker
- Department of Surgery, Division of Surgical Oncology, Oregon Heath & Science University (OHSU), 3181 SW Sam Jackson Park Rd, Mail Code: L-619, Portland, OR, 97239, USA
| | - Alice W Fung
- The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA.,Department of Radiology, OHSU, Portland, OR, 97239, USA
| | - Erin Maynard
- Department of Surgery, Division of Abdominal Organ Transplantation/Hepatobiliary Surgery, OHSU, Portland, OR, 97239, USA
| | - C Kristian Enestvedt
- Department of Surgery, Division of Abdominal Organ Transplantation/Hepatobiliary Surgery, OHSU, Portland, OR, 97239, USA
| | | | | | - Charles D Lopez
- The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA.,Division of Hematology Oncology, OHSU, Portland, OR, 97239, USA
| | - Susan L Orloff
- Department of Surgery, Division of Abdominal Organ Transplantation/Hepatobiliary Surgery, OHSU, Portland, OR, 97239, USA
| | - Skye C Mayo
- Department of Surgery, Division of Surgical Oncology, Oregon Heath & Science University (OHSU), 3181 SW Sam Jackson Park Rd, Mail Code: L-619, Portland, OR, 97239, USA. .,The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA.
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33
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Chen Y, Weng S. Reappraisal of the T Category for Solitary Intrahepatic Cholangiocarcinoma by Tumor Size in 611 Early-Stage (T1-2N0M0) Patients After Hepatectomy: a Surveillance, Epidemiology, and End Results (SEER) Analysis. J Gastrointest Surg 2021; 25:1989-1999. [PMID: 33140321 DOI: 10.1007/s11605-020-04833-x] [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: 07/18/2020] [Accepted: 10/17/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy is controversial, and the T category in the American Joint Committee on Cancer (AJCC) stage for ICC is a topic of debate. METHODS Data from 611 T1-2N0M0 ICC patients classified by the AJCC 8th edition who underwent hepatectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 1988-2015. Cancer-specific survival was evaluated using Kaplan-Meier analysis. The optimal cutoff value of solitary tumor size was used an adjusted p value approach to discriminating patient survival. RESULTS In the AJCC 8th staging system, using a 5-cm cut-off value of tumor size for solitary ICC without vascular invasion (S/VI-) was not associated with survival in T1 category (p = 0.201), and multifocal ICC with vascular invasion had a worse survival than solitary ICC with vascular invasion (S/VI+) in T2 category (p = 0.014). Tumor size was a prognostic factor for both S/VI- and S/VI+, the optimal cutoff value of tumor size was obtained 8 cm for S/VI- and 3 cm for S/VI+. S/VI- ≤ 8 cm had a similar survival to S/VI+ ≤ 3 cm (p = 0.126), S/VI- > 8 cm had a similar survival to S/VI+ > 3 cm (p = 0.655), and multifocal ICC had a similar survival with S/VI- > 8 cm (p = 0.159) and S/VI+ > 3 cm (p = 0.196). When the cohort was divided into two groups-new T1 (S/VI- ≤ 8 cm and S/VI+ ≤ 3 cm) and new T2 (S/VI- > 8 cm, S/VI+ > 3 cm and multifocal ICC)-significant survival difference was observed (p < 0.0001). CONCLUSIONS The discriminatory power of the AJCC 8th edition for solitary ICC could be further enhanced by subdividing tumors according to size and vascular invasion (8 cm for S/VI- and 3 cm for S/VI+).
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Affiliation(s)
- YiPing Chen
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian, China
| | - ShanGeng Weng
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian, China.
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34
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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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35
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Massani M, Bonariol L, Stecca T. Hepatic Arterial Infusion Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma, a Comprehensive Review. J Clin Med 2021; 10:2552. [PMID: 34207700 PMCID: PMC8228250 DOI: 10.3390/jcm10122552] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/02/2021] [Accepted: 06/08/2021] [Indexed: 01/03/2023] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common primitive liver cancer. Despite recent advances in the surgical management, the prognosis remains poor, with a 5-year survival rate of less than 5%. Intrahepatic CCA (iCCA) has a median survival between 18 and 30 months, but if deemed unresectable it decreases to 6 months. Most patients have a liver-confined disease that is considered unresectable because of its localization, with infiltration of vascular structures or multifocality. The peculiar dual blood supply allows the delivery of high doses of chemotherapy via a surgically implanted subcutaneous pump, through the predominant arterial tumor vascularization, achieving much higher and more selective tumor drug levels than systemic administration. The results of the latest studies suggest that adequate and early treatment with the combination approach of hepatic arterial infusion (HAI) and systemic (SYS) chemotherapy is associated with improved progression-free and overall survival than SYS or HAI alone for the treatment of unresectable iCCA. Current recommendations are limited by a lack of prospective trials. Individualization of chemotherapy and regimens based on selective targets in mutant iCCA are a focus for future research. In this paper we present a comprehensive review of the studies published to date and ongoing trials.
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Affiliation(s)
- Marco Massani
- HPB Hub Reference Center, First General Surgery Unit, Department of Surgery, Azienda ULSS2 Marca Trevigiana, 31100 Treviso, Italy; (L.B.); (T.S.)
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Lamarca A, Santos‐Laso A, Utpatel K, La Casta A, Stock S, Forner A, Adeva J, Folseraas T, Fabris L, Macias RI, Krawczyk M, Krawczyk M, Cardinale V, Braconi C, Alvaro D, Evert M, Banales JM, Valle JW, for the Group: on behalf of the European Network for the Study of Cholangiocarcinoma (ENS‐CCA). Liver Metastases of Intrahepatic Cholangiocarcinoma: Implications for an Updated Staging System. Hepatology 2021; 73:2311-2325. [PMID: 33073396 PMCID: PMC8252018 DOI: 10.1002/hep.31598] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 08/04/2020] [Accepted: 09/20/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Intrahepatic cholangiocarcinoma (iCCA) with liver metastases is perceived to have a poor prognosis, but the American Joint Committee on Cancer (AJCC) classifies them as early stage in the absence of lymph nodes or extrahepatic spread. APPROACH AND RESULTS Patients with iCCA from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and Surveillance, Epidemiology, and End Results (SEER) registries with survival/staging (AJCC v.7) data were eligible. Modified staging was used (mAJCC v.7): group A: stages I-III (excluding T2bN0); group B: stage IVa (excluding T2bN1M0); group C: liver metastases (T2bN0/1); and group D: stage IVb (extrahepatic metastases). Survival analysis (Kaplan-Meier and Cox regression) was performed in an ENS-CCA training cohort (TC) and findings internally (ENS-CCA iVC) and externally (SEER) validated. The aim was to assess whether liver metastases (group C) had a shorter survival compared to other early stages (group A) to propose a modified version of AJCC v.8 (mAJCC v.8). A total of 574 and 4,171 patients from the ENS-CCA and SEER registries were included. Following the new classification, 19.86% and 17.31% of patients from the ENS-CCA and SEER registries were reclassified into group C, respectively. In the ENS-CCA TC, multivariable Cox regression was adjusted for obesity (p = 0.026) and performance status (P < 0.001); patients in group C (HR, 2.53; 95% CI, 1.18-5.42; P = 0.017) had a higher risk of death (vs. group A). Findings were validated in the ENS-CCA iVC (HR, 2.93; 95% CI, 2.04-4.19; P < 0.001) and in the SEER registry (HR, 1.88; 95% CI, 1.68-2.09; P < 0.001). CONCLUSIONS iCCA with liver metastases has a worse outcome than other early stages of iCCA. Given that AJCC v.8 does not take this into consideration, a modification of AJCC v.8 (mAJCC v.8), including "liver metastases: multiple liver lesions, with or without vascular invasion" as an "M1a stage," is suggested.
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Affiliation(s)
- Angela Lamarca
- Medical Oncology/Institute of Cancer SciencesThe Christie NHS Foundation Trust/University of ManchesterManchesterUnited Kingdom
| | - Alvaro Santos‐Laso
- Department of Liver and Gastrointestinal DiseasesBiodonostia Health Research InstituteDonostia University HospitalUniversity of the Basque Country (UPV/EHU)San SebastianSpain
| | - Kirsten Utpatel
- Institute of PathologyUniversity of RegensburgRegensburgGermany
| | - Adelaida La Casta
- Department of Liver and Gastrointestinal DiseasesBiodonostia Health Research InstituteDonostia University HospitalUniversity of the Basque Country (UPV/EHU)San SebastianSpain
| | - Simone Stock
- Institute of PathologyUniversity of RegensburgRegensburgGermany
| | - Alejandro Forner
- BCLC group, Liver UnitHospital Clínic BarcelonaBarcelonaSpain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd)The National Institute of Health Carlos IIIMadridSpain
| | - Jorge Adeva
- Department of Medical OncologyHospital Universitario 12 de OctubreMadridSpain
| | - Trine Folseraas
- Section of Gastroenterology and the Norwegian PSC Research CenterDepartment of Transplantation MedicineOslo University HospitalOsloNorway
| | - Luca Fabris
- Department of Molecular MedicineUniversity of PaduaPaduaItaly
| | - Rocio I.R. Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd)The National Institute of Health Carlos IIIMadridSpain
- Experimental Hepatology and Drug Targeting (HEVEPHARM) groupUniversity of SalamancaIBSALSalamancaSpain
| | - Marcin Krawczyk
- Department of Medicine IISaarland University Medical CentreSaarland UniversityHomburgGermany
- Laboratory of Metabolic Liver DiseasesCentre for Preclinical ResearchDepartment of General, Transplant and Liver SurgeryMedical University of WarsawWarsawPoland
| | - Marek Krawczyk
- Department of General, Transplant and Liver SurgeryMedical University of WarsawWarsawPoland
| | | | - Chiara Braconi
- Medical OncologyThe University of GlasgowGlasgowUnited Kingdom
| | | | - Matthias Evert
- Institute of PathologyUniversity of RegensburgRegensburgGermany
| | - Jesus M. Banales
- Department of Liver and Gastrointestinal DiseasesBiodonostia Health Research InstituteDonostia University HospitalUniversity of the Basque Country (UPV/EHU)San SebastianSpain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd)The National Institute of Health Carlos IIIMadridSpain
- IKERBASQUEBasque Foundation for ScienceBilbaoSpain
| | - Juan W. Valle
- Medical Oncology/Institute of Cancer SciencesThe Christie NHS Foundation Trust/University of ManchesterManchesterUnited Kingdom
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Lu WF, Chen PQ, Yan K, Wu YC, Liang L, Yuan JY, Fu Y, Zhang HB. Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:575-582. [PMID: 33899638 DOI: 10.1080/17474124.2021.1913053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. METHODS A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed. RESULTS The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RM & MVI (-), 58.0%, 36.1%, and 26.5% in narrow RM & MVI (-), 51.0%, 27.0%, and 24.3% in wide RM & MVI (+), and 39.0%, 20.4% and 14.3% in narrow RM & MVI (+) (p < 0.001). Multivariate analysis showed that RM & MVI were independent risk factors for the OS and RFS. CONCLUSION Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.
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Affiliation(s)
- Wen-Feng Lu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Pei-Qin Chen
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Kai Yan
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Ye-Chen Wu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Jian-Yong Yuan
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Yong Fu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Hai-Bin Zhang
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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Recommended Minimal Number of Harvested Lymph Nodes for Intrahepatic Cholangiocarcinoma. J Gastrointest Surg 2021; 25:1164-1171. [PMID: 32378093 DOI: 10.1007/s11605-020-04622-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 04/20/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Lymph node (LN) metastasis is one factor indicating a poor prognosis after radical surgery for intrahepatic cholangiocarcinoma (ICC). Although several guidelines have recommended that LN dissection be strongly considered at the time of ICC surgery, no clear evidence regarding the appropriate number of harvested LNs has been established. Thus, we aimed to identify the minimum number of harvested LNs required for ICC by using a Bayesian Weibull model. METHODS Data from 142 patients who underwent radical hepatectomy (R0) for ICC from January 2000 to December 2018 were retrospectively reviewed. A Bayesian Weibull model was developed to analyze the effect of number of harvested LNs on survival of patients without (N0; n = 71) and with (N1; n = 71) metastatic nodes. We also compared the percentage of N1 patients (i.e., the N1 rate) in each of the five subgroups categorized according to the number of harvested LNs (1-4, 5-8, 9-12, 13-16, and ≥ 17). RESULTS In patients with 5 or more harvested LNs, the hazard ratio (HR) for LN metastasis was above the reference line (the HR with 5 harvested LNs, 1.95 (1.09-3.45)). The N1 rate of the 1-4 harvested LNs subgroup was lower than that of the other subgroups (e.g., 1-4 vs. 5-8; 16.1% vs. 39.4%, p = 0.014). CONCLUSION Our results suggest that at least 5 LNs should be harvested in patients who undergo radical surgery for ICC to promote accurate staging.
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Park HJ, Park B, Park SY, Choi SH, Rhee H, Park JH, Cho ES, Yeom SK, Park S, Park MS, Lee SS. Preoperative prediction of postsurgical outcomes in mass-forming intrahepatic cholangiocarcinoma based on clinical, radiologic, and radiomics features. Eur Radiol 2021; 31:8638-8648. [PMID: 33890153 DOI: 10.1007/s00330-021-07926-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 03/15/2021] [Accepted: 03/23/2021] [Indexed: 01/06/2023]
Abstract
OBJECTIVES Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features. METHODS This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell's C-index and compared with postoperative prognostic systems. RESULTS A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68; p = 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71; p = 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71-0.73 vs. 0.70-0.73; p ≥ 0.40) and overall survival (C-index, 0.68-0.71 vs. 0.64-0.74; p ≥ 0.27) in the test cohort. CONCLUSIONS A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC. KEY POINTS • The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma. • The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival. • The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Bumwoo Park
- Health Innovation Big Data Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Seo Young Park
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hyungjin Rhee
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suk-Keu Yeom
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Cai Z, He C, Zhao C, Lin X. Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:611118. [PMID: 33868997 PMCID: PMC8047640 DOI: 10.3389/fonc.2021.611118] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 03/18/2021] [Indexed: 12/30/2022] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. Methods Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. Results ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. Conclusions HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.
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Affiliation(s)
- Zhiyuan Cai
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chongyu Zhao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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Zhao J, Chen Y, Wang J, Wang J, Wang Y, Chai S, Zhang Y, Chen X, Zhang W. Preoperative risk grade predicts the long-term prognosis of intrahepatic cholangiocarcinoma: a retrospective cohort analysis. BMC Surg 2021; 21:113. [PMID: 33676467 PMCID: PMC7936481 DOI: 10.1186/s12893-020-00954-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 11/12/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC). METHODS 468 consecutive ICC patients who underwent hepatectomy between 2010 and 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated. RESULTS The PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG = 1: hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI 0.062-0.768) from 0.625 (95% CI 0.585-0.665) when the PRG was incorporated (p < 0.001). CONCLUSIONS The PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC.
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Affiliation(s)
- Jianping Zhao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Yao Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Jingjing Wang
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Wang
- Department of Hepatopancreatobiliary Surgery Treatment Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Ying Wang
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Songshan Chai
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Yuxin Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
| | - Wanguang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
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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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Sutton TL, Billingsley KG, Walker BS, Enestvedt CK, Dewey EN, Orloff SL, Mayo SC. Neoadjuvant chemotherapy is associated with improved survival in patients undergoing hepatic resection for intrahepatic cholangiocarcinoma. Am J Surg 2021; 221:1182-1187. [PMID: 33707077 DOI: 10.1016/j.amjsurg.2021.02.029] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 01/19/2021] [Accepted: 02/25/2021] [Indexed: 01/25/2023]
Abstract
BACKGROUND The impact of neoadjuvant chemotherapy (NAC) on overall and recurrence-free survival (OS, RFS) in resectable intrahepatic cholangiocarcinoma (ICC) is poorly characterized. We sought to investigate the association of NAC with oncologic outcomes in ICC. METHODS We identified n = 52 patients with ICC undergoing hepatectomy from 2004 to 2017. Oncologic outcomes were analyzed using Kaplan-Meier and multivariate Cox proportional hazard modeling. RESULTS The median patient age was 64-years. NAC was administered in ten (19%) patients, most commonly with gemcitabine-cisplatin (n = 8, 80%). Median RFS and OS were 15 months. and 49 months, respectively. Controlling for stage and margins, NAC was independently associated with improved OS (HR 0.16, P = 0.01) but not RFS (HR 0.54, P = 0.27). NAC was not associated with major post-operative complications (P = 0.25) or R1 margins (P = 0.58). CONCLUSION NAC in ICC may hold oncologic benefits beyond downstaging borderline resectable disease, such as identifying patients with favorable biology who are more likely to benefit from resection.
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Affiliation(s)
- Thomas L Sutton
- Oregon Heath & Science University (OHSU), Department of Surgery, Portland, OR, 97239, USA
| | | | - Brett S Walker
- Oregon Heath & Science University (OHSU), Department of Surgery, Portland, OR, 97239, USA
| | - C Kristian Enestvedt
- OHSU, Department of Surgery, Division of Abdominal Transplant, Portland, OR, 97239, USA
| | - Elizabeth N Dewey
- Oregon Heath & Science University (OHSU), Department of Surgery, Portland, OR, 97239, USA
| | - Susan L Orloff
- OHSU, Department of Surgery, Division of Abdominal Transplant, Portland, OR, 97239, USA
| | - Skye C Mayo
- The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA; OHSU, Department of Surgery, Division of Surgical Oncology, Portland, OR, 97239, USA.
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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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45
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Kong J, Cao Y, Chai J, Liu X, Lin C, Wang J, Liu J. Effect of Tumor Size on Long-Term Survival After Resection for Solitary Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 10:559911. [PMID: 33552949 PMCID: PMC7859518 DOI: 10.3389/fonc.2020.559911] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 12/01/2020] [Indexed: 01/12/2023] Open
Abstract
Background The relationship between tumor size and survival in intrahepatic cholangiocarcinoma (ICC) is still controversial. This study aimed to evaluate the prognostic ability of tumor size for solitary ICC after resection and explore optimal cut-off values in different subgroups. Methods Patients with solitary ICC who underwent liver resection from the Surveillance, Epidemiology, and End Results Program and Shandong Provincial Hospital were retrospectively analyzed. Kaplan-Meier and Cox regression analysis were used to assess the prognostic ability of tumor size. The log-rank test was used to determine the optimal cut-off values, and a minimum P was regarded as the optimal one in different subgroups. Results Large tumor size groups had worse overall survival (OS) than small tumor size groups. Cox regression analysis suggested that tumor size was an independent prognostic factor for OS for solitary ICC after resection. Subgroup analysis showed tumor size was associated with OS for both solitary ICC with and without vascular invasion (VI). Furthermore, the optimal cut-off values for solitary ICC with and without VI were found to be 8 and 3 cm, respectively, which could divide the patients into two groups with significant differences in OS. Conclusion Tumor size was an independent prognostic factor for solitary ICC after resection. The existing American Joint Committee on Cancer (AJCC) staging system could be improved if the cut-off value of the T1 stage was changed to 8 cm and if the T2 stage incorporated a tumor size with a cut-off value of 3 cm. Further studies with more cases are needed to validate these findings.
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Affiliation(s)
- Junjie Kong
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yukun Cao
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jiawei Chai
- Department of Breast and Thyroid Surgery, Shandong Maternity and Child Care Hospital, Jinan, China
| | - Xihan Liu
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Cunhu Lin
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jianping Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jun Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Büttner S, Galjart B, Beumer BR, van Vugt JLA, van Eijck CHJ, Polak WG, de Jonge J, Homs MYV, van Driel LMJW, Pawlik TM, Steyerberg EW, Ijzermans JNM, Groot Koerkamp B. Quality and performance of validated prognostic models for survival after resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. HPB (Oxford) 2021; 23:25-36. [PMID: 32855047 DOI: 10.1016/j.hpb.2020.07.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/01/2020] [Accepted: 07/05/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The objective of this systematic review was to evaluate the performance of prognostic survival models for intrahepatic cholangiocarcinoma (iCCA) when validated in an external dataset. Furthermore, it sought to identify common prognostic factors across models, and assess methodological quality of the studies in which the models were developed. METHODS The PRISMA guidelines were followed. External validation studies of prognostic models for patients with iCCA were searched in 5 databases. Model performance was assessed by discrimination and calibration. RESULTS Thirteen external validation studies were identified, validating 18 different prognostic models. The Wang model was the sole model with good performance (C-index above 0.70) for overall survival. This model incorporated tumor size and number, lymph node metastasis, direct invasion into surrounding tissue, vascular invasion, Carbohydrate antigen (CA) 19-9, and carcinoembryonic antigen (CEA). Methodological quality was poor in 11/12 statistical models. The Wang model had the highest score with 13 out of 17 points. CONCLUSION The Wang model for prognosis after resection of iCCA has good quality and good performance at external validation, while most prognostic models for iCCA have been developed with poor methodological quality and show poor performance at external validation.
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Affiliation(s)
- Stefan Büttner
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Boris Galjart
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Berend R Beumer
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | | | | | - Wojciech G Polak
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Timothy M Pawlik
- Department of Surgery, Ohio State Medical Center, Columbus, OH, United States of America
| | - Ewout W Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
| | - Jan N M Ijzermans
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
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47
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Evaluation and Recommendation of the 8th Edition of American Joint Committee on Cancer (AJCC) Staging System for Intrahepatic Cholangiocarcinoma (ICC) in 820 Patients from the Surveillance, Epidemiology, and End Results (SEER) Database. J Gastrointest Surg 2021; 25:145-154. [PMID: 32193847 DOI: 10.1007/s11605-020-04557-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 02/19/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. METHODS Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. RESULTS To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P < 0.05); in N0M0 cohort, there was no significant difference in survival between solitary tumor with vascular invasion and multiple tumors (P = 0.092), tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion (P = 0.470), and tumor with and without periductal invasion (PI) (P = 0.220). The prognosis of patients with ≥ 4 positive lymph nodes was relatively poor compared with 1-3 positive lymph nodes (P = 0.037) and similar to patients with stage IV (8th AJCC, P = 0.585). CONCLUSION This study found that there was no significant difference in survival between tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion, whereas other T staging changes were effective. The inclusion of the number of positive lymph nodes in the 8th AJCC stage may improve prognostic discrimination in ICC patients.
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48
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Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma. J Gastroenterol 2020; 55:1171-1182. [PMID: 33089343 DOI: 10.1007/s00535-020-01729-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 09/13/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery. METHODS Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line. RESULTS Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan-Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (p < 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4-31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6-18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro. CONCLUSIONS Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.
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Wu ZY, Shen W, Yue JQ, Yao WY, Liu SL, Jin YP, Dong P, Ma F, Wu XS, Gong W. Combining Immunoscore with Clinicopathologic Features in Cholangiocarcinoma: An Influential Prognostic Nomogram. Onco Targets Ther 2020; 13:11359-11376. [PMID: 33192071 PMCID: PMC7654544 DOI: 10.2147/ott.s274754] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/21/2020] [Indexed: 02/05/2023] Open
Abstract
PURPOSE The aim of this study was to determine the Immunoscore as an independent prognostic factor for cholangiocarcinoma and establish a useful prognostic model for postoperative patients. METHODS This retrospective study was performed to assess the correlation between the clinicopathological features, tumor immune microenvironment, and prognosis of 76 patients with cholangiocarcinoma. Multivariate analysis was used to identify independent factors significantly associated with local recurrence-free survival (LRFS) and overall survival (OS). Finally, we constructed a nomogram combining the Immunoscore with clinicopathologic features to predict postoperative recurrence and OS. RESULTS The present study showed that immune cell infiltration was negatively correlated with tumor size, peripheral vascular invasion, lymph node metastasis, and tumor staging. Kaplan-Meier curves indicated that a decreased Immunoscore was associated with poor prognosis. Multivariate analysis demonstrated that resection type, number of tumors, lymph node metastasis, TNM staging, and the Immunoscore were significantly associated with LRFS. For OS, the significantly correlated factors included resection type, peripheral vascular invasion, TNM staging, and the Immunoscore. Immunoscore was superior to TNM staging in predicting both LRFS and OS according to the receiver operating characteristic analysis. Based on the results of the Cox regression analysis, a prognostic nomogram for the postoperative recurrence of cholangiocarcinoma and OS of patients was established. CONCLUSION The results of this study suggest that the Immunoscore may be used as an independent predictor of postoperative recurrence and OS of patients with cholangiocarcinoma. The Immunoscore appears to offer distinct advantages over the TNM staging system. By combining the Immunoscore and clinicopathological features, the proposed nomogram provides a more accurate predictive tool for postoperative patients with cholangiocarcinoma.
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Affiliation(s)
- Zi-You Wu
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Wei Shen
- Shanghai Colorectal Cancer Research Center, Shanghai, People’s Republic of China
| | - Juan-Qing Yue
- Department of Pathology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Wen-Yan Yao
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Shi-Lei Liu
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Yun-Peng Jin
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Ping Dong
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Fei Ma
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Xiang-Song Wu
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
| | - Wei Gong
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, People’s Republic of China
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Saleh M, Virarkar M, Bura V, Valenzuela R, Javadi S, Szklaruk J, Bhosale P. Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings. Abdom Radiol (NY) 2020; 45:3662-3680. [PMID: 32417933 DOI: 10.1007/s00261-020-02559-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
To this date, it is a major oncological challenge to optimally diagnose, stage, and manage intrahepatic cholangiocarcinoma (ICC). Imaging can not only diagnose and stage ICC, but it can also guide management. Hence, imaging is indispensable in the management of ICC. In this article, we review the pathology, epidemiology, genetics, clinical presentation, staging, pathology, radiology, and treatment of ICC.
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Affiliation(s)
- Mohammed Saleh
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
| | - Mayur Virarkar
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Vlad Bura
- Department of Radiology, County Clinical Emergency Hospital, 400006, Cluj-Napoca, Cluj, Romania
| | - Raul Valenzuela
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Sanaz Javadi
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Janio Szklaruk
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
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