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Morales-Galicia AE, Rincón-Sánchez MN, Ramírez-Mejía MM, Méndez-Sánchez N. Outcome prediction for cholangiocarcinoma prognosis: Embracing the machine learning era. World J Gastroenterol 2025; 31:106808. [DOI: 10.3748/wjg.v31.i21.106808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/15/2025] [Accepted: 05/12/2025] [Indexed: 06/06/2025] Open
Abstract
We read with great interest the study by Huang et al. Cholangiocarcinoma (CC) is the second most common type of primary liver tumor worldwide. Although surgical resection remains the primary treatment for this disease, almost 50% of patients experience relapse within 2 years after surgery, which negatively affects their prognosis. Key predictors can be used to identify several factors (e.g., tumor size, tumor location, tumor stage, nerve invasion, the presence of intravascular emboli) and their correlations with long-term survival and the risk of postoperative morbidity. In recent years, artificial intelligence (AI) has become a new tool for prognostic assessment through the integration of multiple clinical, surgical, and imaging parameters. However, a crucial question has arisen: Are we ready to trust AI with respect to clinical decisions? The study by Huang et al demonstrated that AI can predict preoperative textbook outcomes in patients with CC and highlighted the precision of machine learning algorithms using useful prognostic factors. This letter to the editor aimed to explore the challenges and potential impact of AI and machine learning in the prognostic assessment of patients with CC.
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Affiliation(s)
| | - Mariana N Rincón-Sánchez
- Faculty of Medicine “Dr. Jose Sierra Flores,” Northeastern University, Tampico 89337, Tamaulipas, Mexico
| | - Mariana M Ramírez-Mejía
- Plan of Combined Studies in Medicine, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04360, Mexico
- Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City 14050, Mexico
| | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04360, Mexico
- Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City 14050, Mexico
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Kawashima J, Endo Y, Woldesenbet S, Khalil M, Akabane M, Cauchy F, Shen F, Maithel S, Popescu I, Kitago M, Weiss MJ, Martel G, Pulitano C, Aldrighetti L, Poultsides G, Ruzzente A, Bauer TW, Gleisner A, Marques H, Groot Koerkamp B, Endo I, Pawlik TM. The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2025; 32:4341-4351. [PMID: 39962005 PMCID: PMC12049291 DOI: 10.1245/s10434-025-17013-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 01/28/2025] [Indexed: 05/06/2025]
Abstract
INTRODUCTION While postoperative adjuvant chemotherapy (AC) is generally recommended for intrahepatic cholangiocarcinoma (ICC), its benefit remains debated. This study aimed to identify patients that may benefit from AC following liver resection of ICC. METHODS Patients who underwent liver resection for ICC between 2000 and 2023 were identified from an international multi-institutional database. Individual multivariable Cox models were used to evaluate the interaction between each prognostic factor and the effect of AC on survival. RESULTS Among 1412 patients, 431 (30.5%) received AC. Both higher tumor burden score (TBS; hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91-1.00; p = 0.033) and metastatic lymph node status (HR 0.58, 95% CI 0.38-0.89; p = 0.014) demonstrated interactions with the survival benefit from receipt of AC. Interaction plots highlighted how AC was associated with improved survival beyond a TBS of approximately 6. Notably, among 555 (39.3%) patients with TBS <6 and N0 or Nx status, 5-year overall survival (OS) was no different between patients who received AC versus individuals who did not (55.1% [95% CI 48.9-62.1] vs. 58.7% [95% CI 49.8-69.2]; p = 0.900). In contrast, among 857 (60.7%) patients with TBS ≥6 or N1 status, AC was associated with improved 5-year OS (30.7% [95% CI 26.2-36.0] vs. 33.0% [95% CI 26.9-40.5]; p = 0.018). CONCLUSIONS TBS and lymph node status may be useful in a multidisciplinary setting to inform decisions about AC planning for ICC patients following curative-intent resection.
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Affiliation(s)
- Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Yutaka Endo
- Department of Transplant Surgery, University of Rochester Medical Center, Rochester, NY, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Mujtaba Khalil
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | | | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | | | | | | | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Ana Gleisner
- Department of Surgery, University of Colorado Denver, Denver, CO, USA
| | - Hugo Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Wu G, Chen X, Luo R, Koh YX, Lim TKH, Chew V, Zhou J, Fan J, Gao Q, Zhu K, Shi R. Histopathologic Grading of Residual Tumor Predicts Survival of Intrahepatic Cholangiocarcinoma Patients Treated With Neoadjuvant Therapy: Major Pathologic Response and Its Clinical Significance. Am J Surg Pathol 2025; 49:578-587. [PMID: 40103370 PMCID: PMC12068548 DOI: 10.1097/pas.0000000000002359] [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] [Indexed: 03/20/2025]
Abstract
Neoadjuvant therapy (NAT) is increasingly used to treat patients with initially unresectable intrahepatic cholangiocarcinoma (iCCA). A histopathologic grading system for residual tumors that can predict patient survival is lacking in the literature. This retrospective study enrolled 151 iCCA patients who received NAT. The percentage of residual viable tumor (%RVT) extent was calculated by RVT surface area/total tumor bed area ×100 and scored in 5% increments. Kaplan-Meier and Cox regression analyses were used to investigate its correlations with recurrence-free survival (RFS) and overall survival (OS). Tumor regression grading by the College of American Pathologists (CAP) and MD Anderson (MDA) methodologies were also validated. A 10% RVT-based tumor regression score (TRS) showed a significant correlation with both OS and RFS. TRS and major pathologic response (mPR) were therefore defined as follows: TRS 1/mPR, tumor with 0 to 10% RVT; TRS 2, more than 10% RVT. Patients graded as TRS 1/mPR had superior OS ( P =0.006) and RFS ( P <0.001) compared with those with TRS 2 in univariate analysis. In a multivariate analysis including ypTNM stages, lymphovascular invasion, and perineural invasion, TRS 1/mPR was also found to be an independent prognostic factor for both OS (hazard ratio [HR]: 0.226; 95% CI: 0.053-0.966, P =0.045) and RFS (HR: 0.474; 95% CI: 0.231-0.974, P =0.042). As for the CAP and MDA grading methodologies, they were found to correlate with RFS (CAP: P =0.002; MDA: P =0.001), but not with OS (CAP: P =0.181; MDA: P =0.09). Our study revealed that a TRS of ≤10% RVT significantly correlates with longer OS and RFS and can be suggested as an mPR in iCCA. This indicator is easily applicable, prognostically relevant, and could be further validated in future prospective clinical trials.
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Affiliation(s)
- Gaohua Wu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Xiufen Chen
- Department of Anatomical Pathology, Singapore General Hospital
| | - Rongkui Luo
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre
| | | | - Valerie Chew
- Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Kai Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute
| | - Ruoyu Shi
- Department of Pathology and Laboratory Medicine, Kandang Kerbau Women’s and Children’s Hospital, Singapore
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Zhou RQ, Yang PJ, Liu TT, Han DD, Liu XL, Liu LG, Si S, Yang SW, Xu SS, Guo YW, Tan HD. Liver transplantation for combined hepatocellular cholangiocarcinoma: Current evidence, selection criteria, and therapeutic controversies. World J Gastrointest Surg 2025; 17:105783. [DOI: 10.4240/wjgs.v17.i5.105783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/09/2025] [Accepted: 04/09/2025] [Indexed: 05/23/2025] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare and aggressive primary liver malignancy characterized by features of both HCC and CCA. Preoperative diagnosis remains challenging because of overlapping imaging and histopathological features, which often lead to misclassification. Although liver resection is the primary curative therapy, the efficacy of liver transplantation (LT) remains controversial. Historically, LT has been considered contraindicated owing to the poor prognosis, high recurrence rate of cHCC-CCA, and the potential for organ wastage. Recent studies have suggested that LT may benefit carefully selected patients, particularly those with early-stage tumors or cirrhosis. However, there is no consensus on the criteria for LT in patients with cHCC-CCA. Lymphadenectomy and vascular resection strategies were discussed along with locoregional and systemic therapies. This review synthesized the current evidence on surgical strategies for cHCC-CCA, focusing on evolving LT criteria and outcomes.
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Affiliation(s)
- Rui-Quan Zhou
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Pei-Jun Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Tian-Tong Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Dong-Dong Han
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xiao-Lei Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Li-Guo Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuang Si
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shi-Wei Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuai-Shuai Xu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yi-Wen Guo
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hai-Dong Tan
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
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Yin JX, Fan X, Chen QL, Chen J, He J. Progress in the application of fludeoxyglucose positron emission tomography computed tomography in biliary tract cancer. World J Hepatol 2025; 17:105446. [DOI: 10.4254/wjh.v17.i5.105446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 04/10/2025] [Accepted: 05/07/2025] [Indexed: 05/27/2025] Open
Abstract
Biliary tract cancer (BTC) is a group of heterogeneous sporadic diseases, including intrahepatic, hilar, and distal cholangiocarcinoma, as well as gallbladder cancer. BTC is characterized by high invasiveness and extremely poor prognosis, with a global increased incidence due to intrahepatic cholangiocarcinoma (ICC). The 18F-fludeoxyglucose positron emission tomography (PET) computed tomography (18F-FDG PET/CT) combines glucose metabolic information (reflecting the glycolytic activity of tumor cells) with anatomical structure to assess tumor metabolic heterogeneity, systemic metastasis, and molecular characteristics noninvasively, overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions. 18F-FDG PET/CT offers critical insights in clinical staging, therapeutic evaluation, and prognostic prediction of BTC. This article reviews research progress in this field over the past decade, with a particular focus on the advances made in the last 3 years, which have not been adequately summarized and recognized. The research paradigm in this field is shifting from qualitative to quantitative studies, and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC. Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis. Additionally, PET/magnetic resonance imaging is increasingly demonstrating its value in this field.
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Affiliation(s)
- Jia-Xin Yin
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Xin Fan
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Qiao-Liang Chen
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Jing Chen
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Jian He
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
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Zeng D, Wang Y, Wen N, Li B, Cheng N, Lu J. Short-term and Long-term Clinical Outcomes of Combined Caudate Lobectomy for Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus: A Propensity Score Analysis. Gut Liver 2025; 19:438-453. [PMID: 39327842 PMCID: PMC12070214 DOI: 10.5009/gnl240158] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/31/2024] [Accepted: 06/09/2024] [Indexed: 09/28/2024] Open
Abstract
Background/Aims Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.
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Affiliation(s)
- Di Zeng
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yaoqun Wang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ningyuan Wen
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Nansheng Cheng
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Jiong Lu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, China
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Scholz C, Gerber TS, Hoppe-Lotichius M, Gröger LK, Renger F, Passalacqua M, Margies R, Straub BK, Foerster F, Weinmann A, Tagkalos E, Bartsch F, Lang H. Extracapsular tumor spread does not influence survival outcomes in resected N1-patients with intrahepatic cholangiocarcinoma- a retrospectively controlled cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:110143. [PMID: 40393142 DOI: 10.1016/j.ejso.2025.110143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/26/2025] [Accepted: 05/08/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Extracapsular tumor spread (ECS) in lymph nodes is a known predictor of recurrence and decreased survival across various malignancies, including breast and head and neck cancers. However, its prognostic value in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing curative surgery has not yet been explored. METHODS A retrospective cohort study was conducted, including all patients with lymph node-positive disease (N1) who underwent curative resection for iCCA between 2008 and November 2023. Patients were followed up for at least one year postoperatively. Cases with ECS-positive lymph nodes (N1/ECS+) were compared to those without extracapsular tumor infiltration (N1/ECS-). Statistical analyses included the T-test for continuous variables and the Chi-square test for categorical variables. Survival outcomes were evaluated using the Kaplan-Meier method. RESULTS 70 patients with N1 disease following potentially curative resection were included. Baseline characteristics were comparable between groups (N1/ECS + n = 30, N1/ECS- n = 40), with no significant differences in age (p = 0.853), resection type (p = 0.511), T-stage (p = 0.785), resection margins (p = 0.687) or the number of tumor-positive lymph nodes (p = 0.052). The median overall survival (OS) was 17.2 months in the N1/ECS + group and 17.3 months in the N1/ECS- group (p = 0.466). Similarly, recurrence-free survival (RFS) was not significantly different, with a median of 4.4 months for N1/ECS + patients versus 7.7 months for N1/ECS- patients (p = 0.335). CONCLUSION Extracapsular tumor spread in lymph nodes was not associated with significant differences in overall or recurrence-free survival in patients with intrahepatic cholangiocarcinoma undergoing curative resection. Based on these findings, ECS does not appear to serve as a prognostic predictor of outcomes in this population.
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Affiliation(s)
| | - Tiemo Sven Gerber
- Institute of Pathology, Germany; Institute of Pathology, Worms Hospital, Worms, Germany.
| | | | | | - Franziska Renger
- Department of General, Visceral and Transplant Surgery, Germany.
| | | | - Rabea Margies
- Department of General, Visceral and Transplant Surgery, Germany.
| | | | - Friedrich Foerster
- 1st Department of Internal Medicine, Gastroenterology and Hepatology of University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
| | - Arndt Weinmann
- 1st Department of Internal Medicine, Gastroenterology and Hepatology of University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany.
| | | | - Fabian Bartsch
- Department of General, Visceral and Transplant Surgery, Germany; Department of General and Visceral Surgery, Hospital 'Barmherzige Brüder' Trier, Trier, Germany.
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, Germany.
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Xu L, Chen Z, Zhu D, Wang Y. The Application Status of Radiomics-Based Machine Learning in Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-Analysis. J Med Internet Res 2025; 27:e69906. [PMID: 40323647 PMCID: PMC12089883 DOI: 10.2196/69906] [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: 12/10/2024] [Revised: 03/06/2025] [Accepted: 04/01/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Over the past few years, radiomics for the detection of intrahepatic cholangiocarcinoma (ICC) has been extensively studied. However, systematic evidence is lacking in the use of radiomics in this domain, which hinders its further development. OBJECTIVE To address this gap, our study delved into the status quo and application value of radiomics in ICC and aimed to offer evidence-based support to promote its systematic application in this field. METHODS PubMed, Web of Science, Cochrane Library, and Embase were comprehensively retrieved to determine relevant original studies. The study quality was appraised through the Radiomics Quality Score. In addition, subgroup analyses were undertaken according to datasets (training and validation sets), imaging sources, and model types. RESULTS Fifty-eight studies encompassing 12,903 patients were eligible, with an average Radiomics Quality Score of 9.21. Radiomics-based machine learning (ML) was mainly used to diagnose ICC (n=30), microvascular invasion (n=8), gene mutations (n=5), perineural invasion (PNI; n=2), lymph node (LN) positivity (n=2), and tertiary lymphoid structures (TLSs; n=2), and predict overall survival (n=6) and recurrence (n=9). The C-index, sensitivity (SEN), and specificity (SPC) of the ML model developed using clinical features (CFs) for ICC detection were 0.762 (95% CI 0.728-0.796), 0.72 (95% CI 0.66-0.77), and 0.72 (95% CI 0.66-0.78), respectively, in the validation dataset. In contrast, the C-index, SEN, and SPC of the radiomics-based ML model for detecting ICC were 0.853 (95% CI 0.824-0.882), 0.80 (95% CI 0.73-0.85), and 0.88 (95% CI 0.83-0.92), respectively. The C-index, SEN, and SPC of ML constructed using both radiomics and CFs for diagnosing ICC were 0.912 (95% CI 0.889-0.935), 0.77 (95% CI 0.72-0.81), and 0.90 (95% CI 0.86-0.92). The deep learning-based model that integrated both radiomics and CFs yielded a notably higher C-index of 0.924 (0.863-0.984) in the task of detecting ICC. Additional analyses showed that radiomics demonstrated promising accuracy in predicting overall survival and recurrence, as well as in diagnosing microvascular invasion, gene mutations, PNI, LN positivity, and TLSs. CONCLUSIONS Radiomics-based ML demonstrates excellent accuracy in the clinical diagnosis of ICC. However, studies involving specific tasks, such as diagnosing PNI and TLSs, are still scarce. The limited research on deep learning has hindered both further analysis and the development of subgroup analyses across various models. Furthermore, challenges such as data heterogeneity and interpretability caused by segmentation and imaging parameter variations require further optimization and refinement. Future research should delve into the application of radiomics to enhance its clinical use. Its integration into clinical practice holds great promise for improving decision-making, boosting diagnostic and treatment accuracy, minimizing unnecessary tests, and optimizing health care resource usage.
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Affiliation(s)
- Lan Xu
- Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zian Chen
- Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Dan Zhu
- Dispensary TCM, Quzhou Municipal Hospital of Traditional Chinese Medicine, Quzhou, China
| | - Yingjun Wang
- Department of Dermatology, Quzhou Municipal Hospital of Traditional Chinese Medicine, Quzhou, China
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9
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Kawashima J, Endo Y, Woldesenbet S, Khalil M, Akabane M, Cauchy F, Shen F, Maithel S, Popescu I, Kitago M, Weiss MJ, Martel G, Pulitano C, Aldrighetti L, Poultsides G, Ruzzente A, Bauer TW, Gleisner A, Marques H, Groot Koerkamp B, Endo I, Pawlik TM. "Biological R2" resection for intrahepatic cholangiocarcinoma: identification of patients at risk for poor oncologic outcomes after curative-intent resection. HPB (Oxford) 2025; 27:619-629. [PMID: 39915216 DOI: 10.1016/j.hpb.2025.01.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/29/2024] [Accepted: 01/12/2025] [Indexed: 05/04/2025]
Abstract
INTRODUCTION We sought to define a cohort of patients with "biological R2" (bR2) resection, defined as recurrence within 12 weeks, following curative-intent resection for intrahepatic cholangiocarcinoma (ICC). In addition, we sought to identify factors associated with bR2 risk. METHODS Patients who underwent upfront curative-intent surgery for ICC were identified from an international, multi-institutional database. The weighted beta-coefficients of preoperative risk factors were used to construct an online tool to predict bR2. RESULTS Among 1138 patients, 106 (9.3 %) patients had a bR2 resection. Patients with bR2 were more likely to be younger (OR 0.97) and non-White (OR 2.19), as well as more often had cirrhosis (OR 2.11), a higher neutrophil-to-lymphocyte ratio (OR 1.07), a higher tumor burden score (OR 1.16), and metastatic nodal disease on preoperative imaging (OR 1.92). Patients categorized as low-risk had a 3.2 % risk of bR2, intermediate-risk patients had an 11.1 % risk of bR2, whereas patients in the high-risk category had a 27.6 % risk of bR2 (p < 0.001). An online tool was made available at https://junkawashima.shinyapps.io/bR2_ICC/, https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/. CONCLUSIONS Approximately one in ten patients with resectable ICC had a bR2 resection. An online calculator can may help clinicians identify patients with ICC at highest risk of a bR2 resection.
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Affiliation(s)
- Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA; Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Yutaka Endo
- Department of Transplant Surgery, University of Rochester Medical Center, Rochester, NY, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Mujtaba Khalil
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | - 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, Northwell Health, New Hyde Park, NY, USA
| | | | - Carlo Pulitano
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | | | | | | | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Ana Gleisner
- Department of Surgery, University of Colorado, Denver, CO, USA
| | - Hugo Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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10
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Wu S, Wang M, Zhou Q, Tang H, Wang Z. The Expression and Clinicopathological Significance of BRAF V600E and Mucin 6 in Intrahepatic Cholangiocarcinoma: A Retrospective Study. Int J Surg Pathol 2025; 33:399-407. [PMID: 39246028 DOI: 10.1177/10668969241266930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
Aim. The study aims to explore the expression levels and clinicopathological significance of BRAF V600E and mucin 6 in intrahepatic cholangiocarcinoma. Method. Immunohistochemistry for BRAF V600E and mucin 6 was performed in 110 patients with intrahepatic cholangiocarcinoma. Subsequently, a comprehensive review of medical records and clinicopathological analysis was undertaken. Results. BRAF V600E expression was detected in 11 patients (10%); mucin 6 expression was observed in 19 intrahepatic cholangiocarcinoma specimens (17%). Thereafter, Cox regression models indicated that positive expression of either MUC6 positive (hazard ratio = 0.091, 95% confidence interval = 0.034-0.247, P < .001) and BRAF V600E positive (hazard ratio =0.150, 95% confidence interval = 0.058-0.388, P < .001) was significantly linked with longer overall survival for intrahepatic cholangiocarcinoma patients. Conclusion. The study concludes that positive expression of BRAF V600E and mucin 6 could potentially implied significant survival benefits for patients diagnosed with intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Shurui Wu
- Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China
| | - Meihong Wang
- Department of Pathology, The Hospital of PLA 80th Group Army, Shandong, China
| | - Qinghai Zhou
- Department of Hepatobiliary Surgery, Qianjiang River Hospital for Nationalities, Chongqing, China
| | - Haowen Tang
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Zhanbo Wang
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
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11
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Kierans AS, Cunha GM, King MJ, Marks RM, Miller FH, Lee JM, Qayyum A. Standardized reporting of intrahepatic cholangiocarcinoma. Abdom Radiol (NY) 2025; 50:1584-1594. [PMID: 39373770 DOI: 10.1007/s00261-024-04582-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/08/2024] [Accepted: 09/09/2024] [Indexed: 10/08/2024]
Affiliation(s)
| | | | | | - Robert M Marks
- University of California San Diego Medical Center, San Diego, USA
| | | | - Jeong Min Lee
- Seoul National University Hospital, Seoul, Republic of Korea
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12
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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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13
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Lang SQ, Kong JJ, Li GB, Liu J. Prognostic value of CRP-albumin-lymphocyte index in patients with intrahepatic cholangiocarcinoma after radical resection. Front Med (Lausanne) 2025; 12:1543665. [PMID: 40115790 PMCID: PMC11922830 DOI: 10.3389/fmed.2025.1543665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 02/24/2025] [Indexed: 03/23/2025] Open
Abstract
Purpose The aim of this study is to explore the prognostic value of CRP-Albumin-Lymphocyte (CALLY) index in patients undergoing radical resection of intrahepatic cholangiocarcinoma (ICC). Patients and methods Retrospectively collected clinical data of 286 patients with ICC who underwent radical surgery at Shandong Provincial Hospital from July 2010 to July 2021. Univariate and multivariate analyses were used to evaluate the correlation between the CALLY index and overall survival (OS) and recurrence-free survival (RFS), and a nomogram prediction model was established based on the results. The accuracy of the model was evaluated using concordance index (C-index), calibration curves, decision curve analysis (DCA), and the receiver operating characteristic (ROC) curve was used to compare the prognostic value of the nomogram model with the TNM staging system. Results The optimal cut-off value of CALLY index was 1.81. In the training set, multifactorial Cox regression analysis showed that CALLY index <1.81 was an independent risk factor for OS and RFS (p < 0.05). Compared to neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and modified Glasgow prognostic score (mGPS), CALLY index had a higher area under the curve (AUC). The nomogram established based on the results of multifactorial analysis demonstrated strong efficacy in survival prediction, and the ROC curve showed that the nomogram had a higher prognostic value than TNM staging. Conclusion The CALLY index is independently associated with OS and RFS in patients after radical resection of ICC, and the nomogram model based on it shows significantly higher efficacy in predicting the long-term prognosis of patients after radical resection of ICC, and is more accurate than TNM staging.
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Affiliation(s)
- Shi-Qian Lang
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jun-Jie Kong
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Guang-Bing Li
- 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 Affiliated to Shandong First Medical University, Jinan, China
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14
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Qian X, Ni X, Miao G, Wang F, Zhou C, Huang P, Zhang Y, Chen L, Yang C, Zeng M. Association Between MRI-Based Radiomics Features and Regional Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma and Its Clinical Outcome. J Magn Reson Imaging 2025; 61:997-1010. [PMID: 38923735 DOI: 10.1002/jmri.29477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Regional lymph node metastasis (LNM) assessment is crucial for predicting intrahepatic cholangiocarcinoma (iCCA) prognosis. However, imaging assessment has limitations for identifying LNM. PURPOSE To investigate the association between MRI radiomics features, regional LNM status, and prognosis in iCCA. STUDY TYPE Retrospective. SUBJECTS Two hundred ninety-six patients (male = 197) with surgically confirmed iCCA. FIELD STRENGTH/SEQUENCE 1.5 T and 3.0 T. DWI, T2WI, and contrast-enhanced T1WI. ASSESSMENT Clinical information, radiologic, and MRI-based radiomics features associated with LNM status were collected to establish models. Performance of MRI, PET/CT, and the combined LNM models were compared in training (N = 207) and test (N = 89) datasets. Overall survival (OS) was compared based on LNM status. STATISTICAL TESTS The independent features were selected by 5-fold cross-validation. The performance of MRI, PET/CT, and the models was evaluated using the area under receiver operating characteristic curve (AUC). Univariable and multivariable Cox regression were used to identify independent variables for OS. Kaplan-Meier curves were compared with the log-rank test between LNM positive and negative groups. P < 0.05 was considered statistically significant. RESULTS Intrahepatic duct dilatation, enhancement pattern, and CA19-9 were independent clinicoradiologic features. The radiomics model was constructed by the independent radiomics features extracted from T2WI and delay phase T1WI. The combined LNM model showed AUC of 0.888, 0.884, and 0.811 in training, validation, and test cohorts with a positive net benefit. PET/CT exhibited similar sensitivity to the combined LNM model (0.750 vs. 0.733, P > 0.999) while the combined LNM model showed higher specificity (0.703 vs. 0.630, P = 0.039) in the test cohort. High risk of regional LNM was significantly associated with worse OS (median: 24 months) than low risk (median: 30 months, P < 0.0001). DATA CONCLUSIONS The combined LNM model has the strongest correlation with LNM status for mass-forming iCCA patients. EVIDENCE LEVEL 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Xianling Qian
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Ni
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gengyun Miao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fang Wang
- Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yunfei Zhang
- Shanghai Institute of Medical Imaging, Shanghai, China
- Central Research Institute, United Imaging Healthcare, Shanghai, China
| | - Lei Chen
- Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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15
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Malik AK, Davidson BR, Manas DM. Surgical management, including the role of transplantation, for intrahepatic and peri-hilar cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108248. [PMID: 38467524 DOI: 10.1016/j.ejso.2024.108248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 02/28/2024] [Accepted: 03/03/2024] [Indexed: 03/13/2024]
Abstract
Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.
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Affiliation(s)
- Abdullah K Malik
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; NIHR Blood and Transplant Research Unit, Newcastle University and Cambridge University, Newcastle Upon Tyne, UK.
| | - Brian R Davidson
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK; Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Derek M Manas
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; NIHR Blood and Transplant Research Unit, Newcastle University and Cambridge University, Newcastle Upon Tyne, UK; NHS Blood and Transplant, Bristol, UK
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16
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Colangelo M, Di Martino M, Polidoro MA, Forti L, Tober N, Gennari A, Pagano N, Donadon M. Management of intrahepatic cholangiocarcinoma: a review for clinicians. Gastroenterol Rep (Oxf) 2025; 13:goaf005. [PMID: 39867595 PMCID: PMC11769681 DOI: 10.1093/gastro/goaf005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 11/12/2024] [Accepted: 12/18/2024] [Indexed: 01/28/2025] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy that arises from second-order biliary epithelial cells. Its incidence is gradually increasing worldwide. Well-known risk factors have been described, although in many cases, they are not identifiable. Treatment options are continuously expanding, but the prognosis of iCCA remains dismal. R0 liver resection remains the only curative treatment, but only a limited number of patients can benefit from it. Frequently, major hepatectomies are needed to completely remove the tumour. This could contraindicate surgery or increase postoperative morbidity in patients with chronic liver disease and small remnant liver volume. In cases of anticipated inadequate future liver remnant, regenerative techniques may be used to expand resectability. The role and extent of lymphadenectomy in iCCA are still matters of debate. Improvements in iCCA diagnosis and better understanding of genetic profiles might lead to optimized surgical approaches and drug therapies. The role of neoadjuvant and adjuvant therapies is broadening, gaining more and more acceptance in clinical practice. Combining surgery with locoregional therapies and novel drugs, such as checkpoint-inhibitors and molecular-targeted molecules, might improve treatment options and survival rates. Liver transplantation, after very poor initial results, is now receiving attention for the treatment of patients with unresectable very early iCCA (i.e. <2 cm) in cirrhotic livers, showing survival outcomes comparable to those of hepatocellular carcinoma. Ongoing prospective protocols are testing the efficacy of liver transplantation for patients with unresectable, advanced tumours confined to the liver, with sustained response to neoadjuvant treatment. In such a continuously changing landscape, the aim of our work is to review the state-of-the-art in the surgical and medical treatment of iCCA.
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Affiliation(s)
- Matteo Colangelo
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Marcello Di Martino
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Laura Forti
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
| | - Nastassja Tober
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
| | - Alessandra Gennari
- Division of Oncology, University Maggiore Hospital della Carità, Novara, Italy
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Nico Pagano
- Division of Gastroenterology, University Maggiore Hospital della Carità, Novara, Italy
| | - Matteo Donadon
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Surgery, University Maggiore Hospital della Carità, Novara, Italy
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17
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Khomiak A, Ghaffar SA, Rodriguez Franco S, Ziogas IA, Cumbler E, Gleisner AL, Del Chiaro M, Schulick RD, Mungo B. Prognostic Significance of Lymph Node Ratio in Intrahepatic and Extrahepatic Cholangiocarcinomas. Cancers (Basel) 2025; 17:220. [PMID: 39858002 PMCID: PMC11764393 DOI: 10.3390/cancers17020220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/07/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004-2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan-Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson-Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6-2.7) and HR 2.94 (95% CI 2.3-3.8)) and ECC (HR 2.1 (95% CI 1.8-2.5) and HR 3 (95% CI 2.4-3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Benedetto Mungo
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA; (A.K.)
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Girod BJ, Kandathil A. A review of F-18 fluorodeoxyglucose PET/CT in the evaluation and treatment of hepatobiliary tumors. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:245-258. [PMID: 39846364 DOI: 10.23736/s1824-4785.24.03574-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2025]
Abstract
Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) pose significant diagnostic and therapeutic challenges. Magnetic resonance imaging (MRI) and multiphase computed tomography (CT) have been the preferred imaging modalities for diagnosis, staging, and surveillance of patients with these malignancies. The best clinical outcomes depend on the appropriate selection of treatment options from the tools available in neo-adjuvant therapy, surgical resection, locoregional therapy, liver transplantation, and adjuvant therapy. While not a part of the routine diagnostic work-up or follow-up, F-18 fluorodeoxyglucose positron emission tomography (FDG PET/CT) can inform therapeutic decision making and help avoid futile surgeries by detecting unsuspected distant metastases. Additionally, metabolic information obtained with FDG PET/CT has prognostic value, predicting treatment response and survival. In patients with HCC metabolic parameters obtained by FDG PET/CT have been shown to correlate with microvascular invasion and predict recurrence in orthotopic transplant recipients. This article will highlight studies that have evaluated the role of FDG PET/CT in diagnosis, staging and therapeutic response assessment in patients with hepatobiliary cancers.
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Affiliation(s)
- Bradley J Girod
- Nuclear Medicine, Radiology, University of Texas Southwestern, Dallas, TX, USA -
| | - Asha Kandathil
- Nuclear Medicine, Radiology, University of Texas Southwestern, Dallas, TX, USA
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19
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Zhang R, Tan Y, Liu M, Wang L. Lymph node metastasis of intrahepatic cholangiocarcinoma: the present and prospect of detection and dissection. Eur J Gastroenterol Hepatol 2024; 36:1359-1369. [PMID: 39475782 PMCID: PMC11527382 DOI: 10.1097/meg.0000000000002856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/06/2024] [Indexed: 11/02/2024]
Abstract
Intrahepatic cholangiocarcinoma (ICC) ranks as the second most primary liver cancer that often goes unnoticed with a high mortality rate. Hepatectomy is the main treatment for ICC, but only 15% of patients are suitable for surgery. Despite advancements in therapeutic approaches, ICC has an unfavorable prognosis, largely due to lymph node metastasis (LNM) that is closely linked to the elevated recurrence rates. Consequently, the identification of precise and suitable techniques for the detection and staging of LNM assumes paramount importance for ICC therapy. While preoperative imaging plays a crucial role in ICC diagnosis, its efficacy in accurately diagnosing LNM remains unsatisfactory. The inclusion of lymph node dissection as part of the hepatectomy procedures is significant for the accurate pathological diagnosis of LNM, although it continues to be a topic of debate. The concept of sentinel lymph node in ICC has presented a novel and potentially valuable approach for diagnosing LNM. This review aims to explore the current state and prospects of LNM in ICC, offering a promising avenue for enhancing the clinical diagnosis and treatment of ICC to improve patient prognosis.
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Affiliation(s)
- Ruoyu Zhang
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
| | - Yunfei Tan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute
| | - Mei Liu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
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20
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Pan YJ, Wu SJ, Zeng Y, Cao ZR, Shan Y, Lin J, Xu PJ. Intra- and Peri-tumoral Radiomics Based on Dynamic Contrast Enhanced-MRI to Identify Lymph Node Metastasis and Prognosis in Intrahepatic Cholangiocarcinoma. J Magn Reson Imaging 2024; 60:2669-2680. [PMID: 38609076 DOI: 10.1002/jmri.29390] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (iCCA) affects treatment strategies and prognosis. However, preoperative imaging is not reliable enough for identifying LNM. PURPOSE To develop and validate a radiomics nomogram based on dynamic contrast enhanced (DCE)-MR images for identifying LNM and prognosis in iCCA. STUDY TYPE Retrospective. SUBJECTS Two hundred four patients with pathologically proven iCCA who underwent curative-intent resection and lymphadenectomy (training cohort: N = 107, internal test cohort: N = 46, and external test cohort: N = 51). FIELD STRENGTH/SEQUENCE T1- and T2-weighted imaging, diffusion-weighted imaging and DCE imaging at 1.5 T or 3.0 T. ASSESSMENT Radiomics features were extracted from intra- and peri-tumoral regions on preoperative DCE-MR images. Imaging features were evaluated by three radiologists, and significant variables in univariable and multivariable regression analysis were included in clinical model. The best-performing radiomics signature and clinical characteristics (intrahepatic duct dilatation, MRI-reported LNM) were combined to build a nomogram. Patients were divided into high-risk and low-risk groups based on their nomogram scores (cutoff = 0.341). Patients were followed up for 1-102 months (median 12) after surgery, the overall survival (OS) and recurrence-free survival (RFS) were calculated. STATISTICAL TESTS Receiver operating characteristic (ROC) curve, calibration, decision curve, Delong test, Kaplan-Meier curves, log rank test. Two tailed P < 0.05 was considered statistically significant. RESULTS The nomogram incorporating intra- and peri-tumoral radiomics features, intrahepatic duct dilatation and MRI-reported LNM obtained the best discrimination for LNM, with areas under the ROC curves of 0.946, 0.913, and 0.859 in the training, internal, and external test cohorts. In the entire cohort, high-risk patients had significantly lower RFS and OS than low-risk patients. High-risk of LNM was an independent factor of unfavorable OS and RFS. DATA CONCLUSION The nomogram integrating intra- and peri-tumoral radiomics signatures has potential to identify LNM and prognosis in iCCA. EVIDENCE LEVEL 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Yi-Jun Pan
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Sun-Jie Wu
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yan Zeng
- Department of Research Center, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Zi-Rui Cao
- Department of Research Center, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Yan Shan
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Jiang Lin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Peng-Ju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
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21
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Toshida K, Itoh S, Iseda N, Izumi T, Bekki Y, Yoshiya S, Toshima T, Iwasaki T, Oda Y, Yoshizumi T. The Association of Transferrin Receptor with Prognosis and Biologic Role in Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2024; 31:8627-8637. [PMID: 39179864 DOI: 10.1245/s10434-024-16065-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 08/05/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated. METHODS The study enrolled 92 ICC patients who had undergone hepatic resection. Immunohistochemistry (IHC) assays were performed for TFR protein expression. The regulation of malignant activity and the effect on sensitivity to the ferroptosis-inducer artesunate by TFR were investigated in vitro. RESULTS Using IHC staining, 23 patients were categorized as TFR-positive. The TFR-positive group had a significantly larger tumor size and more microscopic vascular invasion. In the multivariate analysis, TFR positivity was an independent poor prognostic factor. In vitro TFR-knockdown (KD) significantly decreased the intracellular iron levels and the cell proliferation, migration, and invasion rates. Artesunate treatment significantly decreased cell viability, whereas cisplatin promoted ferroptosis. When iron transport into cells was inhibited by TFR-KD, ferroptosis was significantly suppressed. Expression of PD-L1 was induced by cisplatin, with a further increase observed when artesunate and cisplatin were used in combination. CONCLUSIONS Transferrin receptor is a poor prognostic factor for ICC and contributes to sensitivity to ferroptosis.
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Affiliation(s)
- Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuma Izumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuki Bekki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Iwasaki
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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22
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Jiang H, Gao B, Meng Z, Wang Y, Jiao T, Li J, Li X, Cao Y, Zhang X, Li C, Lu S. Integrative multi-omics analysis reveals the role of tumor-associated endothelial cells and their signature in prognosis of intrahepatic cholangiocarcinoma. J Transl Med 2024; 22:948. [PMID: 39427165 PMCID: PMC11490089 DOI: 10.1186/s12967-024-05750-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 10/08/2024] [Indexed: 10/21/2024] Open
Abstract
This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune cells within the tumor microenvironment (TME) and its impact on tumor prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, and lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients to reveal the role of TECs in tumor angiogenesis and their significant heterogeneity. Meanwhile, we identified genes highly expressed in TECs and constructed TEC signatures (TEC.Sig). Next, we calculated TEC scores of samples based on TEC.Sig. Patients with higher TEC scores exhibited a higher frequency of KRAS mutations, which was associated with increased infiltration of neutrophils and immature dendritic cells (iDCs), and decreased numbers of natural killer (NK), CD4 + T, and CD8 + T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations and CXCL12 overexpression showed a contrasting trend. Spatial transcriptomics analysis and histological experiments further confirmed that TECs interacted with various tumor-killing immune cells through the CXCL12/CXCR4 axis. Multiple tumor immunotherapy datasets confirmed that the TEC.Sig could predict patient responses to immunotherapy. The TEC score is a promising and reliable biomarker for predicting genetic mutations and prognosis in ICC patients. Enhancing the regulation of the CXCL12/CXCR4 signaling pathway may represent a potential novel therapeutic target for ICC treatment.
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Affiliation(s)
- Hao Jiang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
| | - Biao Gao
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Nankai University School of Medicine, Nankai University, Tianjin, China
| | - Zihe Meng
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
- College of Basic Medical Science, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Yafei Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Tianyu Jiao
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
| | - Junfeng Li
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
| | - Xuerui Li
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Nankai University School of Medicine, Nankai University, Tianjin, China
| | - Yinbiao Cao
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China
| | - Xianzhou Zhang
- Department of Hepatic Biliary Pancreatic Surgery, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, Henan, China.
| | - Chonghui Li
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China.
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China.
| | - Shichun Lu
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China.
- Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
- Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA, Beijing, China.
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23
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Schleimer LE, Kalvin HL, Ellis RJ, Kingham TP, Soares KC, D'Angelica MI, Balachandran VP, Drebin J, Cercek A, Abou-Alfa GK, O'Reilly EM, Harding JJ, Gönen M, Wei AC, Jarnagin WR. Has Management of Intrahepatic Cholangiocarcinoma Evolved with the Evidence? Trends and Practice Patterns from the National Cancer Database. Ann Surg Oncol 2024; 31:6551-6563. [PMID: 39042229 DOI: 10.1245/s10434-024-15724-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 06/19/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND Management of intrahepatic cholangiocarcinoma (IHC) has advanced in recent decades, including randomized trial evidence supporting systemic therapy in the palliative and adjuvant setting. Mounting observational evidence suggests resection of IHC with multifocal disease (IHC-MF) or lymph node metastasis (IHC-LNM) should be limited. It is unknown how real-world practice has evolved in light of research advances. This study characterizes trends in management and outcomes of IHC without distant metastasis. METHODS We queried the National Cancer Database (NCDB) for patients treated for IHC without distant metastasis (M0) and identified subgroups with lymph node (cN1) or multifocal hepatic involvement (cT2b). Two-sided Cochran-Armitage tests evaluated trends in initial treating modality and perioperative chemotherapy. Logistic regression evaluated associations with choice of initial treating modality. Overall survival (OS) was evaluated by using Kaplan-Meier methods. RESULTS Between 2004 and 2020, 11,368 patients were treated for IHC without extrahepatic metastasis. Forty-three percent underwent resection. Initial management shifted from resection towards radiation or systemic therapy in IHC-MF and IHC-LNM. Use of perioperative chemotherapy increased from 39% pre-2010 to 70% in 2018-2020 (p < 0.001), most often delivered postoperatively. Across the entire cohort, median OS improved from 16 (95% confidence interval [CI] 15-18) to 27 months (95% CI 26-29). More modest improvements were observed in IHC-MF and IHC-LNM. CONCLUSIONS Use of perioperative chemotherapy has been widely adopted, predating randomized trial evidence in the adjuvant setting. Initial management of IHC-MF and IHC-LNM has shifted from resection to systemic and/or radiation therapy. While OS has improved overall, outcomes of IHC-MF and IHC-LNM remain poor, warranting further investigation.
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Affiliation(s)
- Lauren E Schleimer
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hannah L Kalvin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ryan J Ellis
- Department of Surgery, Indiana University, Indiana, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Andrea Cercek
- Weill Medical College at Cornell University, New York, NY, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ghassan K Abou-Alfa
- Weill Medical College at Cornell University, New York, NY, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Trinity College, Dublin, Ireland
| | - Eileen M O'Reilly
- Weill Medical College at Cornell University, New York, NY, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - James J Harding
- Weill Medical College at Cornell University, New York, NY, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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24
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Chatzipanagiotou OP, Tsilimigras DI, Catalano G, Ruzzenente A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Kitago M, Pawlik TM. Preoperative platelet count as an independent predictor of long-term outcomes among patients undergoing resection for intrahepatic cholangiocarcinoma. J Surg Oncol 2024; 130:1042-1050. [PMID: 39138891 PMCID: PMC11654899 DOI: 10.1002/jso.27806] [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: 05/07/2024] [Accepted: 07/27/2024] [Indexed: 08/15/2024]
Abstract
BACKGROUND AND OBJECTIVES An elevated platelet count may reflect neoplastic and inflammatory states, with cytokine-driven overproduction of platelets. The objective of this study was to evaluate the prognostic utility of high platelet count among patients undergoing curative-intent liver surgery for intrahepatic cholangiocarcinoma (ICC). METHODS An international, multi-institutional cohort was used to identify patients undergoing curative-intent liver resection for ICC (2000-2020). A high platelet count was defined as platelets >300 *109/L. The relationship between preoperative platelet count, cancer-specific survival (CSS), and overall survival (OS) was examined. RESULTS Among 825 patients undergoing curative-intent resection for ICC, 139 had a high platelet count, which correlated with multifocal disease, lymph nodes metastasis, poor to undifferentiated grade, and microvascular invasion. Patients with high platelet counts had worse 5-year (35.8% vs. 46.7%, p = 0.009) CSS and OS (24.8% vs. 39.8%, p < 0.001), relative to patients with a low platelet count. After controlling for relevant clinicopathologic factors, high platelet count remained an adverse independent predictor of CSS (HR = 1.46, 95% CI 1.02-2.09) and OS (HR = 1.59, 95% CI 1.14-2.22). CONCLUSIONS High platelet count was associated with worse tumor characteristics and poor long-term CSS and OS. Platelet count represents a readily-available laboratory value that may preoperatively improve risk-stratification of patients undergoing curative-intent liver resection for ICC.
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Affiliation(s)
| | | | - Giovanni Catalano
- Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA
- Department of SurgeryUniversity of VeronaVeronaItaly
| | | | | | - Matthew Weiss
- Department of SurgeryJohns Hopkins HospitalBaltimoreMarylandUSA
| | - Todd W. Bauer
- Department of SurgeryUniversity of VirginiaCharlottesvilleVirginiaUSA
| | | | | | | | | | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred HospitalUniversity of SydneySydneyNew South WalesAustralia
| | - Feng Shen
- Department of SurgeryEastern Hepatobiliary Surgery HospitalShanghaiChina
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver TransplantationAP‐HP, Beaujon HospitalClichyFrance
| | - Bas Groot Koerkamp
- Department of SurgeryErasmus University Medical CentreRotterdamThe Netherlands
| | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohamaJapan
| | | | - Timothy M. Pawlik
- Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA
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25
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Neuzillet C, Decraecker M, Larrue H, Ntanda-Nwandji LC, Barbier L, Barge S, Belle A, Chagneau C, Edeline J, Guettier C, Huguet F, Jacques J, Le Bail B, Leblanc S, Lewin M, Malka D, Ronot M, Vendrely V, Vibert É, Bureau C, Bourliere M, Ganne-Carrie N, Blanc JF. Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF). Liver Int 2024; 44:2517-2537. [PMID: 38967424 DOI: 10.1111/liv.15948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/13/2024] [Accepted: 04/11/2024] [Indexed: 07/06/2024]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.
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Affiliation(s)
- Cindy Neuzillet
- GI Oncology, Medical Oncology Department, Institut Curie, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France
| | - Marie Decraecker
- Oncology Digestive Unit, INSERM U1312, University Hospital of Bordeaux, Bordeaux, France
| | - Hélène Larrue
- Department of Hepatology, University Hospital, Toulouse III-Paul Sabatier University, Toulouse, France
| | | | - Louise Barbier
- New Zealand Liver Transplant Unit and HPB Surgery, Te Toka Tumai, University of Auckland, Auckland, New Zealand
| | - Sandrine Barge
- Centre Hospitalier Intercommunal Créteil-CHI Créteil, Créteil, France
| | - Arthur Belle
- Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | | | - Julien Edeline
- Department of Medical Oncology, CLCC Eugène Marquis, COSS-UMR S1242, INSERM, Univ Rennes, Rennes, France
| | - Catherine Guettier
- Department of Pathology, APHP University Paris Saclay, Hôpital Bicetre, Paris, France
| | - Florence Huguet
- Radiation Oncology Department, Tenon Hospital, APHP-Sorbonne University, Paris, France
| | | | - Brigitte Le Bail
- Pathology Department, University Hospital of Bordeaux, Bordeaux, France
| | - Sarah Leblanc
- Gastroenterology Department, Private Hospital Jean Mermoz, Ramsay Santé, Lyon, France
| | - Maïté Lewin
- Service de Radiologie, AP-HP-Université Paris Saclay Hôpital Paul Brousse, Villejuif, France
| | - David Malka
- Medical Oncology Department, Institut Mutualiste Monsouris, Paris, France
| | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, APHP Nord Clichy, University Paris Cité, CRI UMR, Paris, France
| | | | - Éric Vibert
- Centre Hepato-Biliaire, AP-HP-Université Paris Saclay Hôpital Paul Brousse, Villejuif, France
| | - Christophe Bureau
- Department of Hepatology, University Hospital, Toulouse III-Paul Sabatier University, Toulouse, France
| | | | | | - Jean-Frédéric Blanc
- Oncology Digestive Unit, INSERM U1312, University Hospital of Bordeaux, Bordeaux, France
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Liang J, Jiang S, Song J, Chen D, Weng S, Li S, Peng H, Liu Z, Zhang J, Chen Y, Rao S, Chen H, Zhang R, Liu H, Zhang L. Role of [ 18F]FAPI-04 in staging and therapeutic management of intrahepatic cholangiocarcinoma: prospective comparison with [ 18F]FDG PET/CT. EJNMMI Res 2024; 14:81. [PMID: 39256297 PMCID: PMC11387567 DOI: 10.1186/s13550-024-01145-y] [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: 06/04/2024] [Accepted: 08/29/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI-avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann-Whitney U test, and McNemar's test was used to assess the diagnostic accuracy between the two techniques. RESULTS In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. CONCLUSIONS [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. TRIAL REGISTRATION Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.
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Affiliation(s)
- Jiucen Liang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Shuqin Jiang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Jingjing Song
- Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Danyang Chen
- Tumor Research Institute, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Shaojuan Weng
- Tumor Research Institute, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Shuyi Li
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Hao Peng
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Zhidong Liu
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Jing Zhang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Yuanlin Chen
- Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Songquan Rao
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Haipeng Chen
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China
| | - Rusen Zhang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China.
| | - Hao Liu
- Tumor Research Institute, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China.
| | - Linqi Zhang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong, 510095, P.R. China.
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Sposito C, Maspero M, Cucchetti A, Mazzaferro V. A snapshot on current approaches to lymphadenectomy in liver resection for intrahepatic cholangiocarcinoma: results from an international survey. Updates Surg 2024; 76:1797-1805. [PMID: 38713394 PMCID: PMC11455682 DOI: 10.1007/s13304-024-01852-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/10/2024] [Indexed: 05/08/2024]
Abstract
The use of lymphadenectomy (LND) during resection of intrahepatic cholangiocarcinoma (ICC) is still debated, leading to differing practices in different centers and countries. The aim of this study was to assess such differences. A survey on LND for ICC was distributed to the members of the International Hepato-PancreatoBiliary Association (IHPBA) and the Italian Chapter of IHPBA (AICEP). Two-hundred thirty-four surgeons completed the survey (88% males; median age 46 years). Preoperative nodal staging was deemed mandatory/very important by 65%. Adequate LND was defined as hepatoduodenal ligament LND by 33%, LND at specific nodal stations by 28% and retrieval of > 5 nodes by 28%. The decision to perform LND was influenced by comorbidities (48%), chronic liver disease (38%) and satellitosis (32%). Most participants modify perioperative management in case of clinically positive nodes, 50% stating they would give neoadjuvant therapy. The role of LND in clinically node negative disease was adequate staging for 88%, survival benefit for 50.5% and clinical trials eligibility for 18.5%. Our survey confirms heterogeneity in the evaluation of role and extent of LND for ICC, how this relates to subjective perception of importance of LND, and need of a systematic approach in this area.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy.
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
| | - Marianna Maspero
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni, Pierantoni Hospital, Forlì, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori di Milano, Via Venezian 1, 20133, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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28
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Fiz F, Rossi N, Langella S, Conci S, Serenari M, Ardito F, Cucchetti A, Gallo T, Zamboni GA, Mosconi C, Boldrini L, Mirarchi M, Cirillo S, Ruzzenente A, Pecorella I, Russolillo N, Borzi M, Vara G, Mele C, Ercolani G, Giuliante F, Cescon M, Guglielmi A, Ferrero A, Sollini M, Chiti A, Torzilli G, Ieva F, Viganò L. Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model. Ann Surg Oncol 2024; 31:5604-5614. [PMID: 38797789 DOI: 10.1245/s10434-024-15457-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/28/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.
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Affiliation(s)
- Francesco Fiz
- Nuclear Medicine Unit, Department of Diagnostic Imaging, Ente Ospedaliero "Ospedali Galliera", Genoa, Italy
- Department of Nuclear Medicine and Clinical Molecular Imaging, University Hospital, Tübingen, Germany
| | - Noemi Rossi
- MOX Laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy
| | - Serena Langella
- Department of Digestive and Hepatobiliary Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynaecology and Pediatrics, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - Matteo Serenari
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, A. Gemelli Hospital, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Teresa Gallo
- Department of Radiology, Mauriziano Umberto I Hospital, Turin, Italy
| | - Giulia A Zamboni
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - Cristina Mosconi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Luca Boldrini
- Department of Radiology, Radiation Oncology and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | | | - Stefano Cirillo
- Department of Radiology, Mauriziano Umberto I Hospital, Turin, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynaecology and Pediatrics, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - Ilaria Pecorella
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Nadia Russolillo
- Department of Digestive and Hepatobiliary Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Martina Borzi
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - Giulio Vara
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Caterina Mele
- Hepatobiliary Surgery Unit, A. Gemelli Hospital, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, A. Gemelli Hospital, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Matteo Cescon
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Alfredo Guglielmi
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynaecology and Pediatrics, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - Alessandro Ferrero
- Department of Digestive and Hepatobiliary Surgery, Mauriziano Umberto I Hospital, Turin, Italy
| | - Martina Sollini
- Department of Nuclear Medicine, IRCCS San Raffaele, Milan, Italy
- Faculty of Medicine, Università Vita-Salute San Raffaele, Milan, Italy
| | - Arturo Chiti
- Department of Nuclear Medicine, IRCCS San Raffaele, Milan, Italy
- Faculty of Medicine, Università Vita-Salute San Raffaele, Milan, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Francesca Ieva
- MOX Laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy
- CHDS - Center for Health Data Science, Human Technopole, Milan, Italy
| | - Luca Viganò
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Hepatobiliary Unit, Department of Minimally Invasive General and Oncologic Surgery, Humanitas Gavazzeni University Hospital, Bergamo, Italy.
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29
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Sun Y, Jiang W, Duan R, Guan L. Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma. Front Pharmacol 2024; 15:1432603. [PMID: 39170710 PMCID: PMC11335543 DOI: 10.3389/fphar.2024.1432603] [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: 05/14/2024] [Accepted: 07/29/2024] [Indexed: 08/23/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver, following hepatocellular carcinoma (HCC). Surgical resection remains the only potentially curative treatment for ICC. However, due to its high malignancy and propensity for postoperative recurrence, the prognosis for ICC is generally poor, and there is currently little standardized approach for adjuvant therapy following curative surgery. This article aims to explore adjuvant treatment strategies for ICC post-curative surgery by reviewing retrospective studies and clinical trials conducted in recent years. The analysis focuses on the effectiveness, challenges, and potential developments in the management of ICC post-surgery, considering the high recurrence rates and the need for improved therapeutic approaches to enhance patient outcomes. Additionally, we discuss the various types of adjuvant treatments that have been explored, including chemotherapy, radiation therapy, and targeted therapies. The goal is to provide a comprehensive overview of the current landscape and highlight promising directions for future research to improve survival and quality of life for ICC patients.
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Affiliation(s)
| | | | | | - Lianyue Guan
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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30
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Huang G, Xi P, Yao Z, Zhao C, Li X, Lin X. The conditional recurrence-free survival after R0 hepatectomy for locally advanced intrahepatic cholangiocarcinoma: A competing risk analysis based on inflammation-nutritional status. Heliyon 2024; 10:e33931. [PMID: 39055818 PMCID: PMC11269833 DOI: 10.1016/j.heliyon.2024.e33931] [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: 02/27/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Background Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method. Methods We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators. Results Considering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set. Conclusions Conditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.
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Affiliation(s)
- Guizhong Huang
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Pu Xi
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Zehui Yao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Chongyu Zhao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China
| | - Xiaohui Li
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China
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31
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Holzner ML, Mazzaferro V, Busset MDD, Aldrighetti L, Ratti F, Hasegawa K, Arita J, Sapisochin G, Abreu P, Schoning W, Schmelzle M, Nevermann N, Pratschke J, Florman S, Halazun K, Schwartz ME, Tabrizian P. Is Repeat Resection for Recurrent Intrahepatic Cholangiocarcinoma Warranted? Outcomes of an International Analysis. Ann Surg Oncol 2024; 31:4397-4404. [PMID: 38334851 DOI: 10.1245/s10434-024-14975-w] [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: 10/12/2023] [Accepted: 01/12/2024] [Indexed: 02/10/2024]
Abstract
BACKGROUND Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.
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Affiliation(s)
- Matthew L Holzner
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vincenzo Mazzaferro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | - Michele Droz Dit Busset
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Wenzel Schoning
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Mortiz Schmelzle
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Nora Nevermann
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Sander Florman
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Karim Halazun
- NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA
| | - Myron E Schwartz
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Parissa Tabrizian
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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32
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Tsilimigras DI, Endo Y, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Popescu I, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM. Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence. Ann Surg Oncol 2024; 31:4427-4435. [PMID: 38520582 DOI: 10.1245/s10434-024-15210-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/07/2024] [Indexed: 03/25/2024]
Abstract
INTRODUCTION Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. METHODS Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internally validated. RESULTS Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3 months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade (1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrence and carcinoembryonic antigen (CEA) > 5 ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in the PRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). CONCLUSIONS The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrence following initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | | | | | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Alaimo L, Endo Y, Pawlik TM. ASO Author Reflections: Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2024; 31:4464-4465. [PMID: 38261125 PMCID: PMC11164750 DOI: 10.1245/s10434-024-14978-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024]
Affiliation(s)
- Laura Alaimo
- Department of Surgery, Division of Surgical Oncology, The Ohio State University, Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Yutaka Endo
- Department of Surgery, Division of Surgical Oncology, The Ohio State University, Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University, Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
- Department of Surgery, University of Verona, Verona, Italy.
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Kahraman G, Haberal KM, Dilek ON. Imaging features and management of focal liver lesions. World J Radiol 2024; 16:139-167. [PMID: 38983841 PMCID: PMC11229941 DOI: 10.4329/wjr.v16.i6.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/28/2024] [Accepted: 05/22/2024] [Indexed: 06/26/2024] Open
Abstract
Notably, the number of incidentally detected focal liver lesions (FLLs) has increased dramatically in recent years due to the increased use of radiological imaging. The diagnosis of FLLs can be made through a well-documented medical history, physical examination, laboratory tests, and appropriate imaging methods. Although benign FLLs are more common than malignant ones in adults, even in patients with primary malignancy, accurate diagnosis of incidental FLLs is of utmost clinical significance. In clinical practice, FLLs are frequently evaluated non-invasively using ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Although US is a cost-effective and widely used imaging method, its diagnostic specificity and sensitivity for FLL characterization are limited. FLLs are primarily characterized by obtaining enhancement patterns through dynamic contrast-enhanced CT and MRI. MRI is a problem-solving method with high specificity and sensitivity, commonly used for the evaluation of FLLs that cannot be characterized by US or CT. Recent technical advancements in MRI, along with the use of hepatobiliary-specific MRI contrast agents, have significantly improved the success of FLL characterization and reduced unnecessary biopsies. The American College of Radiology (ACR) appropriateness criteria are evidence-based recommendations intended to assist clinicians in selecting the optimal imaging or treatment option for their patients. ACR Appropriateness Criteria Liver Lesion-Initial Characterization guideline provides recommendations for the imaging methods that should be used for the characterization of incidentally detected FLLs in various clinical scenarios. The American College of Gastroenterology (ACG) Clinical Guideline offers evidence-based recommendations for both the diagnosis and management of FLL. American Association for the Study of Liver Diseases (AASLD) Practice Guidance provides an approach to the diagnosis and management of patients with hepatocellular carcinoma. In this article, FLLs are reviewed with a comprehensive analysis of ACR Appropriateness Criteria, ACG Clinical Guideline, AASLD Practice Guidance, and current medical literature from peer-reviewed journals. The article includes a discussion of imaging methods used for the assessment of FLL, current recommended imaging techniques, innovations in liver imaging, contrast agents, imaging features of common nonmetastatic benign and malignant FLL, as well as current management recommendations.
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Affiliation(s)
- Gökhan Kahraman
- Department of Radiology, Suluova State Hospital, Amasya 05500, Türkiye
| | - Kemal Murat Haberal
- Department of Radiology, Başkent University Faculty of Medicine, Ankara 06490, Türkiye
| | - Osman Nuri Dilek
- Department of Surgery, İzmir Katip Celebi University, School of Medicine, İzmir 35150, Türkiye
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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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Huang G, Xi P, Yao Z, Zhao C, Li X, Chen Z, Lin X. The Clinical Association Between the Inflammation-Nutritional Condition and Prognosis of Locally Advanced Intrahepatic Cholangiocarcinoma After R0 Resection: Evidence from Competing Risk and Propensity Matching Analysis. J Inflamm Res 2024; 17:2787-2799. [PMID: 38737115 PMCID: PMC11088411 DOI: 10.2147/jir.s460103] [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: 01/17/2024] [Accepted: 05/01/2024] [Indexed: 05/14/2024] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.
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Affiliation(s)
- Guizhong Huang
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China
| | - Pu Xi
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China
| | - Zehui Yao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China
| | - Chongyu Zhao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
| | - Xiaohui Li
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China
| | - Zexian Chen
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China
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Roth GS, Verlingue L, Sarabi M, Blanc JF, Boleslawski E, Boudjema K, Bretagne-Bignon AL, Camus-Duboc M, Coriat R, Créhange G, De Baere T, de la Fouchardière C, Dromain C, Edeline J, Gelli M, Guiu B, Horn S, Laurent-Croise V, Lepage C, Lièvre A, Lopez A, Manfredi S, Meilleroux J, Neuzillet C, Paradis V, Prat F, Ronot M, Rosmorduc O, Cunha AS, Soubrane O, Turpin A, Louvet C, Bouché O, Malka D. Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT). Eur J Cancer 2024; 202:114000. [PMID: 38493667 DOI: 10.1016/j.ejca.2024.114000] [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: 12/11/2023] [Revised: 02/28/2024] [Accepted: 03/01/2024] [Indexed: 03/19/2024]
Abstract
INTRODUCTION This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.
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Affiliation(s)
- Gael S Roth
- Univ. Grenoble Alpes / Hepato-Gastroenterology and Digestive Oncology department, CHU Grenoble Alpes / Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France
| | - Loic Verlingue
- Medical Oncology Department, Centre Léon Bérard, 28 rue Laennec, Lyon, France
| | - Matthieu Sarabi
- Gastroenterology Department, Hopital privé Jean Mermoz, 69008 Lyon, France
| | | | - Emmanuel Boleslawski
- Univ. Lille, INSERM U1189, CHU Lille, Service de Chirurgie Digestive et Transplantations, Lille, France
| | - Karim Boudjema
- Département de chirurgie viscérale hépatobiliaire, CHU de Rennes, Rennes, France
| | | | - Marine Camus-Duboc
- Endoscopie digestive, Hôpital Saint-Antoine, AP-HP/Sorbonne Université, Paris France
| | - Romain Coriat
- Service de gastroentérologie, d'endoscopie et d'oncologie digestive, Hôpital Cochin, APHP, Paris, France
| | - Gilles Créhange
- Radiation Oncology Department. Paris/Saint-Cloud/Orsay, Institut Curie. PSL Research University, Paris, France
| | - Thierry De Baere
- Département de Radiologie Interventionnelle, Gustave Roussy, 94805 Villejuif, France
| | | | - Clarisse Dromain
- Service de radiodiagnostic et radiologie interventionnelle, Centre Hospitalier Universitaire Vaudois, Switzerland
| | | | - Maximiliano Gelli
- Département de Chirurgie Viscérale, Gustave Roussy, 94805 Villejuif, France
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital - Montpellier School of Medicine, Montpellier, France
| | - Samy Horn
- Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite, France
| | - Valérie Laurent-Croise
- Department of Radiology, Centre Hospitalier Universitaire de Nancy, Hôpital de Brabois, 54500 Vandœuvre-lès-Nancy, France
| | - Côme Lepage
- Université de Bourgogne, CHU Dijon-Bourgogne, INSERM U1231. BP 87 900, 14 rue Paul Gaffarel, 21079 Dijon, France
| | - Astrid Lièvre
- Department of Gastroenterology, Rennes University Hospital, University of Rennes 1, INSERM Unité 1242, Rennes, France
| | - Anthony Lopez
- INSERM U1256, NGERE, Faculty of Medicine, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France; Department of Hepatology and Gastroenterology, Nancy University Hospital, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France, NGERE, Faculty of Medicine, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Sylvain Manfredi
- Université de Bourgogne, CHU Dijon-Bourgogne, INSERM U1231. BP 87 900, 14 rue Paul Gaffarel, 21079 Dijon, France
| | - Julie Meilleroux
- Pathology and Cytology Department, CHU Toulouse, IUCT Oncopole, Toulouse Cedex 9, France
| | - Cindy Neuzillet
- GI Oncology, Department of Medical Oncology, Institut Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France
| | - Valérie Paradis
- Université Paris Cité, APHP.Nord Sce d'Anatomie Pathologique Hôpital Beaujon, Clichy, INSERM UMR 1149, France
| | - Frédéric Prat
- Endoscopie digestive, Hôpital Beaujon, Clichy, France
| | - Maxime Ronot
- Department of Medical Imaging, Beaujon University Hospital, Clichy, France
| | - Olivier Rosmorduc
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM U1193, Université Paris-Saclay, FHU Hépatinov, France
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM U1193, Université Paris-Saclay, FHU Hépatinov, France
| | - Olivier Soubrane
- Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Anthony Turpin
- Department of Medical Oncology, CNRS UMR9020, Inserm UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University Lille, CHU Lille, Lille; GERCOR, Paris, France
| | - Christophe Louvet
- Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France
| | - Olivier Bouché
- Gastroenterology and Digestive Oncology Department, Robert-Debré University Hospital, Reims, France
| | - David Malka
- Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France.
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Alaimo L, Endo Y, Catalano G, Ruzzenente A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Kitago M, Pawlik TM. Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2024; 31:3043-3052. [PMID: 38214817 PMCID: PMC10997542 DOI: 10.1245/s10434-023-14880-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/21/2023] [Indexed: 01/13/2024]
Abstract
INTRODUCTION Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. METHODS Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class <3, body mass index <35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. RESULTS Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0-67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. CONCLUSIONS Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.
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Affiliation(s)
- Laura Alaimo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | | | | | | | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | | | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Tsilimigras DI, Han X, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Chaucy F, Koerkamp BG, Endo I, Sasaki K, Aucejo F, Zhang XF, Zhu H, Pawlik TM. Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features. Ann Surg Oncol 2024; 31:3087-3097. [PMID: 38347332 PMCID: PMC10997729 DOI: 10.1245/s10434-024-15013-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 01/21/2024] [Indexed: 04/08/2024]
Abstract
INTRODUCTION Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Xu Han
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | | | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | | | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Chaucy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kazunari Sasaki
- Department of Surgery, Stanford University, Stanford, CA, USA
| | - Federico Aucejo
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, USA
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hua Zhu
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Stüben BO, Ahmadi S, Saner FH, Li J, Neuhaus JP, Treckmann JW, Hoyer DP. The significance of resection margins on R0 results in intrahepatic cholangiocarcinoma. Surg Oncol 2024; 53:102058. [PMID: 38431994 DOI: 10.1016/j.suronc.2024.102058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 02/01/2024] [Accepted: 02/28/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.
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Affiliation(s)
- B O Stüben
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany.
| | - S Ahmadi
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany
| | - F H Saner
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany; Organ Transplant Center of Excellence, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia
| | - J Li
- Department of Surgery, Jiahui International Hospital, Shanghai, China
| | - J P Neuhaus
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany
| | - J W Treckmann
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany
| | - D P Hoyer
- Department of General-, Visceral- and Transplant Surgery, Medical Centre University Duisburg-Essen, 45147, Essen, Germany
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Ratti F, Maina C, Clocchiatti L, Marino R, Pedica F, Casadei Gardini A, De Cobelli F, Aldrighetti LAM. Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA). Ann Surg Oncol 2024; 31:2557-2567. [PMID: 38165575 DOI: 10.1245/s10434-023-14807-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 12/07/2023] [Indexed: 01/04/2024]
Abstract
BACKGROUND Surgery for intrahepatic cholangiocarcinoma (iCCA) is jeopardized by significant risk of early recurrence (≤ 6 months). The aim of the present study is to analyze the oncological benefit provided by laparoscopic over open approach for iCCA in patients with high risk of very early recurrence (VER). MATERIALS AND METHODS A total of 532 liver resections (LR) were performed for iCCA [265 by minimally invasive surgery (MIS) and 267 with open approach, matched through a 1:1 propensity score] and stratified using the postoperative prediction model of VER. Outcomes were compared between open and laparoscopic approaches, specifically evaluating oncological benefit. RESULTS The percentage of patients with high risk of VER was similar (32.7% in the laparoscopic group and 35.3% in the open group, pNS). The number of retrieved nodes as well as the rate and depth of negative resection margins were comparable between laparoscopic and open. The surgery-adjuvant treatment interval was shorter in laparoscopic patients in the overall series, as well in the subgroup of high risk of VER. The rate of patients starting adjuvant treatments within 2 months from surgery was higher in laparoscopic group compared with open group. In VER high-risk group both disease-free survival (DFS) and overall survival (OS) were significantly improved in MIS compared with open group (p = 0.032 and p = 0.026, respectively). CONCLUSIONS In patients with high risk of VER, laparoscopy translates into an advantage in terms of recurrence-free survival, likely related to lower biological impact of surgery, together with a shorter interval between surgery and start of adjuvant treatments, even allowing for a higher number of patients to start adjuvant therapies within 2 months from resection.
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Affiliation(s)
- Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele, Milan, Italy.
- Vita-Salute San Raffaele University, Milan, Italy.
| | - Cecilia Maina
- Hepatobiliary Surgery Division, IRCCS San Raffaele, Milan, Italy
| | | | - Rebecca Marino
- Hepatobiliary Surgery Division, IRCCS San Raffaele, Milan, Italy
| | - Federica Pedica
- Department of Experimental Oncology, Pathology Unit, San Raffaele Hospital, Milan, Italy
| | - Andrea Casadei Gardini
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy
- Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Cheo FY, Chan KS, Shelat VG. Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis. World J Virol 2024; 13:88946. [PMID: 38616852 PMCID: PMC11008402 DOI: 10.5501/wjv.v13.i1.88946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/10/2023] [Accepted: 12/28/2023] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). AIM To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. RESULTS Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. CONCLUSION This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.
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Affiliation(s)
- Feng Yi Cheo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Kai Siang Chan
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Yang Z, Wang L, Zhai Y, Zhao J, Ye F, Wang S, Jiang L, Song Y, Sun Y, Zhu J, Tang Y, Liu Y, Song Y, Fang H, Li N, Qi S, Lu N, Li YX, Zhao H, Chen B. Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma. Clin Transl Radiat Oncol 2024; 45:100749. [PMID: 38425471 PMCID: PMC10904232 DOI: 10.1016/j.ctro.2024.100749] [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: 05/07/2023] [Revised: 01/29/2024] [Accepted: 02/15/2024] [Indexed: 03/02/2024] Open
Abstract
Background Scarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. Methods We retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. Results Hepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. Conclusion We provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.
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Affiliation(s)
- Zhuanbo Yang
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yirui Zhai
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Shulian Wang
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Liming Jiang
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yan Song
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yongkun Sun
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Ji Zhu
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yuan Tang
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yueping Liu
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Yongwen Song
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Hui Fang
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Ning Li
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Shunan Qi
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Ningning Lu
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Ye-Xiong Li
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
| | - Bo Chen
- State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), No. 17 Panjiayan Nanli, Chaoyang District, Beijing, China
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Tsung C, Quinn PL, Ejaz A. Management of Intrahepatic Cholangiocarcinoma: A Narrative Review. Cancers (Basel) 2024; 16:739. [PMID: 38398130 PMCID: PMC10886475 DOI: 10.3390/cancers16040739] [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: 01/10/2024] [Revised: 02/02/2024] [Accepted: 02/04/2024] [Indexed: 02/25/2024] Open
Abstract
The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.
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Affiliation(s)
- Carolyn Tsung
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (C.T.); (P.L.Q.)
| | - Patrick L. Quinn
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (C.T.); (P.L.Q.)
| | - Aslam Ejaz
- Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA
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Shimamaki Y, Hosokawa I, Takayashiki T, Takano S, Sonoda I, Ohtsuka M. Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma. Surg Case Rep 2024; 10:35. [PMID: 38332333 PMCID: PMC10853132 DOI: 10.1186/s40792-024-01832-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 01/28/2024] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described. CASE PRESENTATION A 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery. CONCLUSIONS In this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.
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Affiliation(s)
- Yoshitaka Shimamaki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Isamu Hosokawa
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Itaru Sonoda
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba, 260-0856, Japan.
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Yeow M, Fong KY, Zhao JJ, Tan AYH, Koh YX, Kam JH, Goh BKP, Pawlik TM, Kabir T. Value of lymph node dissection in intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. HPB (Oxford) 2024; 26:161-170. [PMID: 38071187 DOI: 10.1016/j.hpb.2023.11.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/18/2023] [Accepted: 11/17/2023] [Indexed: 02/02/2024]
Abstract
BACKGROUND The aim of this study was to perform a systematic review and meta-analysis to investigate the impact of lymph node dissection (LND) on outcomes following resection of intrahepatic cholangiocarcinoma (ICC). METHODS PubMed, EMBASE, and Cochrane were searched from inception to 30th January 2023 for studies that compared LND with no LND (NLND) among patients with ICC. To limit the effect of unbalanced covariates, only studies that utilized propensity score-based methods were included. Subgroup analysis of patients with clinically node-negative (cN0) ICC was analyzed. RESULTS Among 3776 patients with ICC, individuals in the LND versus NLND cohorts had comparable overall survival (OS) (Hazard ratio [HR] 0.78, 95 % confidence interval [CI] 0.57-1.06, P = 0.11), disease-free survival (DFS) (HR 0.84, 95 % CI 0.70-1.01, P = 0.07) and risk of major complications (odds ratio [OR] 1.07, 95 % CI 0.70-1.62, P = 0.75). Subgroup analysis of cN0 patients, OS was significantly higher in patients who underwent LND (HR 0.61, 95 % CI 0.50-0.74, P < 0.01), with a non-significant trend towards improved DFS (HR 0.81, 95 % CI 0.65-1.01, P = 0.06). CONCLUSION This study found no differences in long-term survival or morbidity following LND for ICC. Subgroup analysis of cN0 patients, who underwent LND detected improved OS with a trend towards better DFS, compared to patients with NLND.
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Affiliation(s)
- Marcus Yeow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Khi Y Fong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Joseph J Zhao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Hospital, Singapore; National University Cancer Institute, Singapore
| | - Alvin Y Hui Tan
- Department of General Surgery, Sengkang General Hospital, Singapore, Singapore
| | - Ye X Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore
| | - Juinn H Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Department of General Surgery, Sengkang General Hospital, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Tousif Kabir
- Department of General Surgery, Sengkang General Hospital, Singapore, Singapore.
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Eletta OA, Panayotova GG, Lunsford KE. Liver Transplant for Intrahepatic Cholangiocarcinoma. Surg Clin North Am 2024; 104:215-225. [PMID: 37953037 DOI: 10.1016/j.suc.2023.07.006] [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: 11/14/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) tends to be asymptomatic until late stages, leading most of the patients to present at advanced stages of the disease. A combination of medical and surgical therapy is crucial for patient management. Historically, poor outcomes resulted in liver transplantation being formally contraindicated for patients with iCCA; however, recent advances in patient selection and neoadjuvant therapy have resulted in a paradigm shift in liver transplant oncology. As a result, the feasibility of liver transplantation for iCCA is being reevaluated by several centers as a therapeutic alternative for select patients with locally advanced unresectable disease.
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Affiliation(s)
- Olanrewaju A Eletta
- Department of Surgery, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, MEB 596, New Brunswick, NJ 08901, USA
| | - Guergana G Panayotova
- Division of Transplant and HPB Surgery, Department of Surgery Rutgers, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA
| | - Keri E Lunsford
- Division of Transplant and HPB Surgery, Department of Surgery Rutgers, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
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Wu G, Li WY, Gong YX, Lin F, Sun C. Impact of open hepatectomy on postoperative bile leakage in patients with biliary tract cancer. World J Gastrointest Surg 2024; 16:67-75. [PMID: 38328317 PMCID: PMC10845266 DOI: 10.4240/wjgs.v16.i1.67] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/09/2023] [Accepted: 12/20/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Bile leakage is a common and serious complication of open hepatectomy for the treatment of biliary tract cancer. AIM To evaluate the incidence, risk factors, and management of bile leakage after open hepatectomy in patients with biliary tract cancer. METHODS We retrospectively analyzed 120 patients who underwent open hepatectomy for biliary tract cancer from February 2018 to February 2023. Bile leak was defined as bile drainage from the surgical site or drain or the presence of a biloma on imaging. The incidence, severity, timing, location, and treatment of the bile leaks were recorded. The risk factors for bile leakage were analyzed using univariate and multivariate logistic regression analyses. RESULTS The incidence of bile leak was 16.7% (20/120), and most cases were grade A (75%, 15/20) according to the International Study Group of Liver Surgery classification. The median time of onset was 5 d (range, 1-14 d), and the median duration was 7 d (range, 2-28 d). The most common location of bile leakage was the cut surface of the liver (70%, 14/20), followed by the anastomosis site (25%, 5/20) and the cystic duct stump (5%, 1/20). Most bile leaks were treated conservatively with drainage, antibiotics, and nutritional support (85%, 17/20), whereas some required endoscopic retrograde cholangiopancreatography with stenting (10%, 2/20) or percutaneous transhepatic cholangiography with drainage (5%, 1/20). Risk factors for bile leakage include male sex, hepatocellular carcinoma, major hepatectomy, blood loss, and blood transfusion. CONCLUSION Bile leakage is a frequent complication of open hepatectomy for biliary tract cancer. However, most cases are mild and can be conservatively managed. Male sex, hepatocellular carcinoma, major hepatectomy, blood loss, and blood transfusion were associated with an increased risk of bile leak.
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Affiliation(s)
- Gang Wu
- General Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Wen-Ying Li
- General Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Yu-Xing Gong
- General Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Feng Lin
- General Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Chen Sun
- General Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
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Noh S, Ham A, Gil JR, Lee M, Lim T. Intrahepatic cholangiocarcinoma initially diagnosed as adenocarcinoma of unknown primary with hepatoduodenal ligament lymph node metastases: A case report. Oncol Lett 2024; 27:7. [PMID: 38028185 PMCID: PMC10664074 DOI: 10.3892/ol.2023.14140] [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: 05/02/2023] [Accepted: 10/03/2023] [Indexed: 12/01/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) with regional lymph node metastases, which lacks a well-delineated liver mass, may be misdiagnosed as a carcinoma of unknown primary (CUP) origin. The present study reports the case of a 69-year-old man initially diagnosed with CUP, who was incidentally found to have abdominal lymphadenopathy during ultrasonography (US). The clinical course from the time of lymphadenectomy and CUP diagnosis to iCCA detection after long-term follow-up is reported. A patient with a history of hypertensive renal disease presented with an incidental finding of enlarged abdominal lymph nodes in the perihepatic region on US. Abdominal contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed two enlarged lymph nodes in the hepatoduodenal ligament. Exploratory laparotomy and lymphadenectomy were performed for diagnostic and therapeutic purposes, respectively. Poorly differentiated metastatic adenocarcinoma positive for cytokeratin 7 and negative for cytokeratin 20 was identified in two of the 22 lymph nodes. Postoperatively, a positron emission tomography/CT (PET/CT) scan was performed, which failed to locate the primary site. The diagnosis of CUP was confirmed based on clinical, radiological and histopathological characteristics. A sequential abdominal CT scan 48 months after lymphadenectomy revealed a faintly enhancing, intraductal polypoid mass with localized ductal dilatation in liver segment 3. MRI and PET/CT confirmed a mass in the left lobe of the liver. US-guided percutaneous needle biopsy confirmed the presence of moderately differentiated adenocarcinoma. The patient refused surgical treatment because of general weakness caused by Coronavirus disease 2019 infection. The patient received radical radiotherapy and underwent left hepatectomy after recovery of their performance status. Histopathological examination of the surgical specimen demonstrated prevailing fibrosis and mucin accumulation, with scattered cancer cells observed focally in the resected liver specimen owing to the effect of the radiotherapy. Consequently, a definitive diagnosis of primary adenocarcinoma of the intrahepatic bile duct was confirmed. The present report may improve understanding of the pathophysiology and clinical progression of iCCA, with a specific focus on the intraductal growth subtype.
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Affiliation(s)
- Sangik Noh
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Ahrong Ham
- Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University Medical Center, Ewha Womans University College of Medicine, Seoul 07985, Republic of Korea
- Division of Hematology-Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Je Ryung Gil
- Division of Radiology, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Miji Lee
- Department of Pathology, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Taekyu Lim
- Division of Hematology-Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
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Franssen S, Holster JJ, Jolissaint JS, Nooijen LE, Cercek A, D'Angelica MI, Homs MYV, Wei AC, Balachandran VP, Drebin JA, Harding JJ, Kemeny NE, Kingham TP, Klümpen HJ, Mostert B, Swijnenburg RJ, Soares KC, Jarnagin WR, Groot Koerkamp B. Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2024; 31:115-124. [PMID: 37814188 PMCID: PMC10695893 DOI: 10.1245/s10434-023-14409-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 09/18/2023] [Indexed: 10/11/2023]
Abstract
BACKGROUND A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA. METHODS We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center. RESULTS In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p < 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0-13.6%) in the gem-cis group versus 34.3% (95% CI 28.1-41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19-0.39). CONCLUSIONS This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.
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Affiliation(s)
- Stijn Franssen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jessica J Holster
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Joshua S Jolissaint
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lynn E Nooijen
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - James J Harding
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
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